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CompletedNCT03194542Updated Aug 24, 2023Results posted

A Safety and Efficacy Study to Evaluate Luspatercept in Subjects With Myeloproliferative Neoplasm-associated Myelofibrosis Who Have Anemia With and Without Red Blood Cell-transfusion Dependence

A Phase 2 interventional study of Luspatercept in Primary Myelofibrosis and Anemia, sponsored by Celgene. Completed at 47 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-08-24.

Sponsored by Celgene (part of Bristol-Myers Squibb) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
95
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This is a Phase 2, multicenter, open-label study to evaluate the efficacy and safety of luspatercept in subjects with MPN-associated myelofibrosis and anemia with and without RBC-transfusion dependence. The study is divided into a Screening Period, a Treatment Period (consisting of a Primary Phase, a Day 169 Disease Response Assessment, and an Extension Phase), followed by a Posttreatment Follow-up Period.

Read the detailed description

Subjects satisfying the eligibility criteria will be assigned to 1 of the following cohorts (which are enrolling in parallel) based on their eligibility:

  • Cohort 1 (subjects with anemia only that are not currently receiving RBC transfusions) - Cohort 2: (subjects that are RBC-transfusion dependent)
  • Cohort 3A: (subjects on ruxolitinib as part of their standard of care therapy that have anemia only)
  • Cohort 3B: (subjects on ruxolitinib as part of their standard of care therapy that are RBC-transfusion dependent) Overall, the study will enroll approximately 100 subjects worldwide.
02

Conditions studied

  • Primary Myelofibrosis
  • Anemia

Keywords

  • Luspatercept
  • ACE-536
  • Myeloproliferative Neoplasm-Associated Myelofibrosis
  • Primary Myelofibrosis
  • Post-Polycythemia Vera Myelofibrosis
  • Post-Essential Thrombocythemia
  • Anemia
  • Red Blood Cell (RBC) Transfusion
  • Ruxolitinib
03

In context

Primary Myelofibrosis

431 studies on the registry are indexed under Primary Myelofibrosis; 118 are open to participants now.

This study's enrollment of 95 is above the median of 44 across 355 interventional studies indexed under Primary Myelofibrosis.

Browse Primary Myelofibrosis studies →

Lead sponsor

Celgene is the lead sponsor of 428 studies on the registry; 12 are open to participants now.

Of its 104 completed or terminated interventional studies of FDA-regulated products, 30 (29%) have results posted.

First submitted before Celgene became part of Bristol-Myers Squibb.

Browse Celgene studies →All Bristol-Myers Squibb studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Subjects must satisfy the following criteria to be enrolled in the study (with the enrollment date defined as the date in which the subject is assigned a cohort in Integrated Response Technology [IRT]) and receive their first dose of luspatercept:

  1. Subject is ≥18 years of age at the time of signing the informed consent form (ICF).
  2. Subject has Myeloproliferative neoplasm (MPN)-associated myelofibrosis (PMF, post- Post-polycythemia vera myelofibrosis (PV MF), and/or Post-essential thrombocythemia myelofibrosis (post-ET MF)) as confirmed from the most recent local bone marrow biopsy report according to the World Health Organization 2016 criteria.

  3. Subject has anemia defined as:

    1. Cohorts 1 and 3A

      • Obtain ≥ 3 Hemoglobin (Hgb) levels of ≤ 9.5 g/dL recorded on ≥ 3 different days, including the day of dosing, in the 84-day period immediately up to the C1D1 date. There must be ≥ 14 days in between each Hgb measurement. No subjects with an interval ≥ 42 days between hemoglobin measurements will be enrolled.
      • There must not be any Red blood cell (RBC) transfusions within the 84-day period immediately up to the C1D1 date.

    2. Cohorts 2 and 3B

      • Average RBC-transfusion frequency: 4 to 12 RBC units/84 days immediately up to the C1D1 date. There must be no interval > 56 days without ≥ 1 RBC-transfusion.
      • Subjects must have a Hgb value of \< 13 g/dL on C1D1 prior to luspatercept administration.
      • Only RBC transfusions given when the Hgb ≤ 9.5 g/dL are scored in determining eligibility.
  4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
  5. Subject is not anticipated during the 6 months from the C1D1 date to receive a hematopoietic cell transplant.

  6. A female of childbearing potential (FCBP) for this study is defined as a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). FCBP participating in the study must:

    1. Have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence* from heterosexual contact.
    2. Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception** without interruption, 28 days prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks (approximately 5 times the mean terminal halflife of luspatercept based on multiple-dose pharmacokinetics [PK] data) after discontinuation of study therapy.

  7. Male subjects must:

    a. Practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks (approximately 5 times the mean terminal half-life of luspatercept based on multiple-dose PK data) following investigational product discontinuation, even if he has undergone a successful vasectomy

  8. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
  9. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion criteria

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment (with the enrollment date defined as the date in which the subject is assigned a cohort in Integrated Response Technology (IRT)):

  1. Subject use of hydroxyurea or other drugs with potential effects on hematopoiesis or ongoing adverse events from previous treatment ≤ 112 days immediately up to the enrollment date.

    a. Systemic corticosteroids are permitted for nonhematological conditions providing the subject is receiving a stable or decreasing dose for ≥ 84 days immediately up to enrollment and is receiving a constant dose equivalent to ≤ 10 mg prednisone for the 28 days immediately up to enrollment.

  2. Cohort 1 and 2 only: subjects treated with Janus kinase 2 gene (JAK2) inhibitors ≤ 112 days immediately up to the enrollment date or if anticipated/substantial likelihood for subject to receive ruxolitinib within the first 168 days on the study.

  3. Cohort 3 only: subjects not receiving ruxolitinib:

    1. for at least 280 days (40 weeks) without interruptions exceeding 2 consecutive weeks
    2. on a stable daily dose for at least 112 days (16 weeks) immediately up to the enrollment date as part of their standard-of-care therapy.
  4. Subject use of ESAs or androgenic steroids ≤ 112 days immediately up to the enrollment date.
  5. Initiation of iron chelation therapy (ICT) or change with ICT dose within ≤ 112 days up to the enrollment date.
  6. Subject with anemia from iron deficiency, B12 and folate deficiencies, hemolytic anemia, infection, or bleeding.
  7. Pregnant or breastfeeding females.
  8. Subject with blood myeloblasts ≥ 5%.
  9. Subject with major surgery within 8 weeks up to the enrollment date. Subject must have completely recovered from any previous surgery immediately up to the enrollment date.

  10. Subject with prior history of malignancies, other than disease under study, unless the subject has been free of the disease for ≥ 5 years. However, subject with the following history/concurrent conditions is allowed:

    • Basal or squamous cell carcinoma of the skin
    • Carcinoma in situ of the cervix
    • Carcinoma in situ of the breast
    • Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)
  11. Subject with prior therapy of luspatercept or sotatercept.
  12. Subject participation in any other clinical protocol or investigational trial that involves administration of experimental therapy and/or therapeutic devices within 30 days immediately up to the enrollment date.
  13. Subject with prior hematopoietic cell transplant.

  14. Subject with any of the following laboratory abnormalities:

    • Neutrophils \< 1 x 109/L
    • White blood count (WBC) > 100 x 109/L

    • Platelets

      • Cohorts 1 and 2: \< 25 x 109/L
      • Cohort 3A and 3B: \< 50 x 109/L
      • All Cohorts: > 1000 x 109/L
    • Estimated glomerular filtration rate \< 45 mL/min/1.73 m2 (via the 4-variable modification of diet in renal disease [Modification of diet in renal disease (MDRD)] formula)
    • Aspartate aminotransferase (AST) or alanine transaminase (ALT) > 3.0 x upper limit of normal (ULN)

    • Direct bilirubin ≥ 2 x ULN

      • higher levels are acceptable if these can be attributed to active red blood cell precursor destruction within the bone marrow (ie, ineffective erythropoiesis)
    • Uncontrolled hyperthyroidism or hypothyroidism
  15. Subject with stroke, deep venous thrombosis, pulmonary or arterial embolism within 6 months immediately up to the enrollment date.
  16. Subject with diastolic blood pressure ≥ 90 mmHg or systolic blood pressure ≥ 140 mmHg measured during the Screening Period despite appropriate treatment.
  17. Subject with inadequately controlled heart disease and/or have a known left ventricular ejection fraction \<35%.
  18. Subject with history of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product (see luspatercept Investigator's Brochure (IB)).
  19. Subject with uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment).
  20. Subject with human immunodeficiency virus (HIV), evidence of active infectious Hepatitis B (HepB), and/or evidence of active Hepatitis C (HepC).
  21. Subject with any significant medical condition, laboratory abnormality, psychiatric illness, or is considered vulnerable by local regulations (eg, imprisoned or institutionalized) that would prevent the subject from participating in the study.
  22. Subject with any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
  23. Subject with any condition or concomitant medication that confounds the ability to interpret data from the study.
  24. Subject on anticoagulant therapy not under appropriate control or subject not on a stable dose of anticoagulant therapy for ≥ 8 weeks up to the enrollment date.
  25. Subject on anagrelide within 28 days immediately up to the enrollment date.
  26. Subject with a major bleeding event (defined as symptomatic bleeding in a critical area or organ and/or bleeding causing a decrease in hemoglobin of ≥ 2g/dL or leading to transfusion of ≥ 2 units of packed red cells) in the last 6 months prior to enrollment.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
95 participants (actual)

Study arms

  • Experimental
    Luspatercept in subjects with MPN-associated myelofibrosis

    Subjects across each of the cohorts (Cohort 1, Cohort 2, Cohort 3A, and Cohort 3B) will receive luspatercept.

    Drug: Luspatercept

Interventions

  • DrugLuspatercept

    Luspatercept is a recombinant fusion protein consisting of a modified form of the extracellular domain of the human active in receptor type IIB linked to the IgG1 Fc domain. Luspatercept, through a mechanism of action different from erythropoietin, works to correct ineffective erythropoiesis by promoting late-stage maturation of erythroblasts.

    Also known as: ACE-536

06

What researchers measure

Primary outcomes

  1. The Number of Participants With Anemia Responses Over Any 84-Day Period During the Primary Treatment Period

    The number of participants that achieved anemia response as it relates to hemoglobin (Hgb) increase and red blood cell (RBC)-transfusion independence is defined below: Cohorts 1 (anemia only) and 3A: The number of participants achieving ≥ 1.5 g/dL hemoglobin increase from baseline over any consecutive 84-day period without an RBC transfusion from Day 1 up through and including Day 168. Cohorts 2 (RBC-transfusion dependent) and 3B: The number of participants who become RBC-transfusion free over any consecutive 84-day period from Day 1 up through and including Day 168. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose.

    Time frame: Any consecutive "rolling" 84-day period from Day 1 through and including Day 168

Secondary outcomes

  1. Time to Anemia Response During the Primary Treatment Period

    Time to anemia response follows the definitions below: Cohorts 1 (anemia only) and 3A: Time between first administration of luspatercept and the first hemoglobin increase of ≥ 1.5 g/dL from baseline that starts a consecutive 84-day period of consecutive increase ≥ 1.5 g/dL without RBC transfusions. Cohorts 2 (RBC-transfusion dependent) and 3B: Time between first administration of luspatercept and the first day of an RBC transfusion-free period of 84 days. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose.

    Time frame: From first dose up to first onset of anemia response (calculated from Day 1 through and including Day 168)

  2. Duration of Anemia Response

    The duration of anemia response is defined as the duration of time from first day of longest response to the last day of longest response. Participants who achieved and maintained the anemia response at the time of the analysis are censored at the efficacy cutoff date. For Cohorts 1 and 3A, an anemia responder was defined as a subject with ≥ 1.5 g/dL hemoglobin increase from baseline over any consecutive 84-day period without an RBC transfusion. For Cohorts 2 and 3B, an anemia responder was defined as a subject who becomes RBC transfusion free over any consecutive 84-day period. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose.

    Time frame: From first dose through last day of longest response (calculated from Day 1 through end of treatment, up to approximately 232 weeks)

  3. The Number of RBC Units Transfused Per Participant Per 28 Days (Cohorts 2 and 3B Only)

    Frequency of RBC transfusion is defined as the mean number of RBC units transfused per participant every 4 weeks (28 days). The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment.

    Time frame: From Day 1 through end of treatment (up to approximately 232 weeks).

  4. The Number Participants Achieving >=50% RBC Transfusion Burden Reduction From Baseline Over Any 84-Day Period (Cohorts 2 and 3B Only)

    The number of participants who reduce their transfusion burden by ≥ 50% from baseline over any consecutive 84-day period. Baseline is defined as average number of RBC units per 28 days over the 84 days period on or prior to the C1D1 date. The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment.

    Time frame: Baseline and from Day 1 through end of treatment (up to approximately 232 weeks).

  5. The Number of Participants Who Achieve ≥ 50% Reduction in Fatigue Symptom as Measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)

    Symptoms response improvement will be assessed using the number of participants who achieve ≥ 50% reduction in fatigue symptoms. Fatigue is 1 out of 10 total symptoms scored on a 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be). The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. Baseline is defined as the last value on or before the first dose of study drug. Last Available = Last available assessment on or before the end of the treatment period. Mean = Mean value of the weekly assessments over the treatment period.

    Time frame: Baseline and from Day 1 through end of treatment (up to approximately 232 weeks)

  6. The Number of Participants Who Achieve ≥ 50% Reduction in Total Symptom Score (TSS) as Measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)

    TSS includes 10 items - worst fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers, scored on a 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be). For participants who completed at least six of these 10 items, the MPN-SAF TSS was computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus had a possible range of 0 to 100. The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. Baseline is defined as the last value on or before the first dose of study drug. Last Available = Last available assessment on or before the end of the treatment period. Mean = Mean value of the weekly assessments over the treatment period.

    Time frame: Baseline and from Day 1 through end of treatment (up to approximately 232 weeks)

  7. Mean Changes in the Functional Assessment of Cancer Therapy - Anemia (FACT-An) Total Scores Over the Study Compared to Baseline

    The Functional Assessment of Cancer Therapy - Anemia (FACT-An) questionnaire includes 47 items rating on a 5-point Likert scale from 0 (not at all) to 4 (very much) on five primary subscales: * Physical well-being (sum of 7 items, score range from 0-28) * Social/Family well-being (sum of 7 items, score range from 0-28) * Emotional well-being (sum of 6 items, score range from 0-24) * Functional well-being (sum of 7 items, score range from 0-28) * Anemia-related symptoms (sum of 20 items, score range from 0-80) A total score for the FACT-An can be calculated by summing the five primary subscales with a score range from 0-188. Higher scores representing better quality of life. Baseline is defined as the last value on or before the first dose of study drug.

    Time frame: Day 169 and End of treatment (up to approximately 232 weeks)

  8. Mean Change in EQ-5D-5L Utility Score Compared to Baseline

    The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. The EQ-5D-5L health utility index for this analysis will be derived using the United Kingdom (UK) value sets based on UK time trade-off (TTO) valuation techniques and will use the Decision Support Unit (DSU) model to cross-walk to the EQ-5D-3L value set from the UK to derive a single index value. The EQ-5D-3L health utility index based on the UK population weights range from -0.594 to 1.0 with higher scores indicating higher health utility.

    Time frame: Day 169 and End of treatment (up to approximately 232 weeks)

  9. The Number of Participants Treatment-Emergent Adverse Events (TEAE)

    TEAE is defined as any AEs that begin or worsen on or after the day of the first dose. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. An SAE is any AE occurring at any dose that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or constitutes an important medical event. The severity/intensity of AEs will be graded based on the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) where Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.

    Time frame: From first dose through 42 days after the last dose (up to approximately 238 weeks)

  10. CL/F (L/Day)

    Apparent clearance

    Time frame: C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.

  11. V1/F (L)

    Apparent volume of distribution of the central compartment

    Time frame: C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.

  12. Ka (Day-1)

    First-order rate constant of absorption

    Time frame: C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.

  13. T1/2 (Day)

    Elimination half-life

    Time frame: C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.

  14. Tmax (Day)

    Time to reach the maximum concentration for the first dose (Cmax)

    Time frame: C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.

  15. Cmax (µg/mL)

    Maximum concentration for the first dose

    Time frame: C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.

  16. Cmax.ss (µg/mL)

    Maximum concentration for the first dose (Cmax) at steady state for the starting dose

    Time frame: C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.

  17. AUCss (Day* µg/mL)

    Area under the concentration-time curve at the steady state for the starting dose

    Time frame: C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.

  18. The Number of Participants With Antidrug Antibody (ADA) Measurements

    The ADA status of a participant during treatment is determined based on the longitudinal ADA results as follows: Negative: All samples (baseline and post-baseline) are negative. Positive to treatment-emergent ADA: At least one post-baseline sample is positive if the baseline sample is negative, or at least one post-baseline sample is positive with a titer ≥ 4-fold of the baseline titer if the baseline sample is positive

    Time frame: C1D1 (pre- dose), C2D1, C4D1, C6D1, C8D1, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.

  19. Mean Changes in Hemoglobin Over the Study Compared to Baseline in the Absence of RBC Transfusions (Cohorts 1 and 3A)

    Calculated based on average hemoglobin measurements collected during the treatment period.The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. The baseline RBC transfusion is defined as average number of RBC units/28 days over the 84 days period immediately prior to the C1D1 date.

    Time frame: Baseline and Day 1 through end of treatment (up to approximately 232 weeks)

  20. The Number of Participants With a Mean Hemoglobin Increase >= 1.5 g/dL From Baseline Over Any Consecutive 84-day Period (Cohorts 1 and 3A)

    The number of participants with a Mean hemoglobin increase of ≥ 1.5 g/dL from baseline over any consecutive 84-day period without an RBC transfusion. The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. Baseline is defined as all non-missing Hgb records within 28 days on or prior to date of first dose (or date of enrollment if not treated).

    Time frame: Baseline and Day 1 through end of treatment (up to approximately 232 weeks)

07

Results

Posted Aug 24, 2023

Participant flow

Participant flow — Overall Study
MilestoneCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Started22211438
Completed0000
Not completed22211438
Withdrew: Participant to receive bone marrow transplant1000
Withdrew: Rollover to long-term follow-up protocol1105
Withdrew: Per protocol repeat blasts of 10%1010
Withdrew: Loss of response4234
Withdrew: Physician decision0100
Withdrew: Lack of efficacy2226
Withdrew: Withdrawal by subject2154
Withdrew: Progressive disease1011
Withdrew: Adverse event1205
Withdrew: Death1205
Withdrew: Completed the primary treatment phase but did not meet clinical benefit criteria81028

Outcome measures

PrimaryThe Number of Participants With Anemia Responses Over Any 84-Day Period During the Primary Treatment Period

The number of participants that achieved anemia response as it relates to hemoglobin (Hgb) increase and red blood cell (RBC)-transfusion independence is defined below: Cohorts 1 (anemia only) and 3A: The number of participants achieving ≥ 1.5 g/dL hemoglobin increase from baseline over any consecutive 84-day period without an RBC transfusion from Day 1 up through and including Day 168. Cohorts 2 (RBC-transfusion dependent) and 3B: The number of participants who become RBC-transfusion free over any consecutive 84-day period from Day 1 up through and including Day 168. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose.

Time frame:
Any consecutive "rolling" 84-day period from Day 1 through and including Day 168
Reported as:
Count of participants · Participants
The Number of Participants With Anemia Responses Over Any 84-Day Period During the Primary Treatment Period
ParticipantsCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
The Number of Participants With Anemia Responses Over Any 84-Day Period During the Primary Treatment Period32210
SecondaryTime to Anemia Response During the Primary Treatment Period

Time to anemia response follows the definitions below: Cohorts 1 (anemia only) and 3A: Time between first administration of luspatercept and the first hemoglobin increase of ≥ 1.5 g/dL from baseline that starts a consecutive 84-day period of consecutive increase ≥ 1.5 g/dL without RBC transfusions. Cohorts 2 (RBC-transfusion dependent) and 3B: Time between first administration of luspatercept and the first day of an RBC transfusion-free period of 84 days. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose.

Time frame:
From first dose up to first onset of anemia response (calculated from Day 1 through and including Day 168)
Reported as:
Mean · Days
Time to Anemia Response During the Primary Treatment Period
DaysCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Time to Anemia Response During the Primary Treatment Period57.3 ± 14.362.0 ± 0.0063.5 ± 30.4130.7 ± 27.22
SecondaryDuration of Anemia Response

The duration of anemia response is defined as the duration of time from first day of longest response to the last day of longest response. Participants who achieved and maintained the anemia response at the time of the analysis are censored at the efficacy cutoff date. For Cohorts 1 and 3A, an anemia responder was defined as a subject with ≥ 1.5 g/dL hemoglobin increase from baseline over any consecutive 84-day period without an RBC transfusion. For Cohorts 2 and 3B, an anemia responder was defined as a subject who becomes RBC transfusion free over any consecutive 84-day period. Baseline value is defined as the last value (including "unscheduled") measured on or before the first dose.

Time frame:
From first dose through last day of longest response (calculated from Day 1 through end of treatment, up to approximately 232 weeks)
Reported as:
Mean · Days
Duration of Anemia Response
DaysCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Duration of Anemia Response457.7 ± 611.20623.0 ± 29.7088.5 ± 6.36534.7 ± 527.67
SecondaryThe Number of RBC Units Transfused Per Participant Per 28 Days (Cohorts 2 and 3B Only)

Frequency of RBC transfusion is defined as the mean number of RBC units transfused per participant every 4 weeks (28 days). The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment.

Time frame:
From Day 1 through end of treatment (up to approximately 232 weeks).
Reported as:
Mean · RBC Units
The Number of RBC Units Transfused Per Participant Per 28 Days (Cohorts 2 and 3B Only)
RBC UnitsCohort 2: RBC-Transfusion DependentCohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Primary Treatment Period2.76 ± 1.9671.49 ± 1.345
Entire Treatment Period2.70 ± 2.0401.52 ± 1.365
SecondaryThe Number Participants Achieving >=50% RBC Transfusion Burden Reduction From Baseline Over Any 84-Day Period (Cohorts 2 and 3B Only)

The number of participants who reduce their transfusion burden by ≥ 50% from baseline over any consecutive 84-day period. Baseline is defined as average number of RBC units per 28 days over the 84 days period on or prior to the C1D1 date. The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment.

Time frame:
Baseline and from Day 1 through end of treatment (up to approximately 232 weeks).
Reported as:
Count of participants · Participants
The Number Participants Achieving >=50% RBC Transfusion Burden Reduction From Baseline Over Any 84-Day Period (Cohorts 2 and 3B Only)
ParticipantsCohort 2: RBC-Transfusion DependentCohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Primary Treatment Period1019
Entire Treatment Period1020
SecondaryThe Number of Participants Who Achieve ≥ 50% Reduction in Fatigue Symptom as Measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)

Symptoms response improvement will be assessed using the number of participants who achieve ≥ 50% reduction in fatigue symptoms. Fatigue is 1 out of 10 total symptoms scored on a 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be). The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. Baseline is defined as the last value on or before the first dose of study drug. Last Available = Last available assessment on or before the end of the treatment period. Mean = Mean value of the weekly assessments over the treatment period.

Time frame:
Baseline and from Day 1 through end of treatment (up to approximately 232 weeks)
Reported as:
Count of participants · Participants
The Number of Participants Who Achieve ≥ 50% Reduction in Fatigue Symptom as Measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
ParticipantsCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Primary Treatment Period (Last Available)42410
Entire Treatment Period (Last Available)4147
Primary Treatment Period (Mean)5135
Entire Treatment Period (Mean)4035
SecondaryThe Number of Participants Who Achieve ≥ 50% Reduction in Total Symptom Score (TSS) as Measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)

TSS includes 10 items - worst fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers, scored on a 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be). For participants who completed at least six of these 10 items, the MPN-SAF TSS was computed as the average of the observed items multiplied by 10 to achieve a 0-to-100 scale. The MPN-SAF TSS thus had a possible range of 0 to 100. The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. Baseline is defined as the last value on or before the first dose of study drug. Last Available = Last available assessment on or before the end of the treatment period. Mean = Mean value of the weekly assessments over the treatment period.

Time frame:
Baseline and from Day 1 through end of treatment (up to approximately 232 weeks)
Reported as:
Count of participants · Participants
The Number of Participants Who Achieve ≥ 50% Reduction in Total Symptom Score (TSS) as Measured by the Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
ParticipantsCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Primary Treatment Period (Last Available)2229
Entire Treatment Period (Last Available)2127
Primary Treatment Period (Mean)2236
Entire Treatment Period (Mean)2236
SecondaryMean Changes in the Functional Assessment of Cancer Therapy - Anemia (FACT-An) Total Scores Over the Study Compared to Baseline

The Functional Assessment of Cancer Therapy - Anemia (FACT-An) questionnaire includes 47 items rating on a 5-point Likert scale from 0 (not at all) to 4 (very much) on five primary subscales: * Physical well-being (sum of 7 items, score range from 0-28) * Social/Family well-being (sum of 7 items, score range from 0-28) * Emotional well-being (sum of 6 items, score range from 0-24) * Functional well-being (sum of 7 items, score range from 0-28) * Anemia-related symptoms (sum of 20 items, score range from 0-80) A total score for the FACT-An can be calculated by summing the five primary subscales with a score range from 0-188. Higher scores representing better quality of life. Baseline is defined as the last value on or before the first dose of study drug.

Time frame:
Day 169 and End of treatment (up to approximately 232 weeks)
Reported as:
Mean · Score on a scale
Mean Changes in the Functional Assessment of Cancer Therapy - Anemia (FACT-An) Total Scores Over the Study Compared to Baseline
Score on a scaleCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Day 169-10.4 ± 13.23-15.7 ± 14.24-9.4 ± 9.245.0 ± 21.77
End of Treatment-15.9 ± 18.35-16.6 ± 16.80-12.6 ± 10.03-14.2 ± 21.98
SecondaryMean Change in EQ-5D-5L Utility Score Compared to Baseline

The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. The EQ-5D-5L health utility index for this analysis will be derived using the United Kingdom (UK) value sets based on UK time trade-off (TTO) valuation techniques and will use the Decision Support Unit (DSU) model to cross-walk to the EQ-5D-3L value set from the UK to derive a single index value. The EQ-5D-3L health utility index based on the UK population weights range from -0.594 to 1.0 with higher scores indicating higher health utility.

Time frame:
Day 169 and End of treatment (up to approximately 232 weeks)
Reported as:
Mean · Score on a scale
Mean Change in EQ-5D-5L Utility Score Compared to Baseline
Score on a scaleCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Day 169-0.043 ± 0.1466-0.063 ± 0.1152-0.126 ± 0.12460.005 ± 0.1084
End of Treatment-0.029 ± 0.1029-0.120 ± 0.1740-0.129 ± 0.1812-0.103 ± 0.2055
SecondaryThe Number of Participants Treatment-Emergent Adverse Events (TEAE)

TEAE is defined as any AEs that begin or worsen on or after the day of the first dose. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. An SAE is any AE occurring at any dose that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or constitutes an important medical event. The severity/intensity of AEs will be graded based on the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) where Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.

Time frame:
From first dose through 42 days after the last dose (up to approximately 238 weeks)
Reported as:
Count of participants · Participants
The Number of Participants Treatment-Emergent Adverse Events (TEAE)
ParticipantsCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Participants with at Least One TEAE21191336
Participants with at Least One Treatment-Related TEAE145719
Participants with at Least One Serious TEAE88417
Participants with at Least One Treatment-Related Serious TEAE1002
Participants with at Least One TEAE Grade >=3911424
Participants with at Least One Treatment-Related TEAE Grade >=30127
Participants with at Least One TEAE Leading to Dose Interruption22312
Participants with at Least One Treatment-Related TEAE Leading to Dose Interruption1114
Participants with at Least One TEAE Leading to Dose Reduction1022
Participants with at Least One Treatment-Related TEAE Leading to Dose Reduction1022
Participants with at Least One TEAE Leading to Study Drug Withdrawn1215
Participants with at Least One Treatment-Related TEAE Leading to Study Drug Withdrawn0001
Participants with at Least One TEAE Leading to Death1205
Participants with at Least One Treatment-Related TEAE Leading to Death0000
SecondaryCL/F (L/Day)

Apparent clearance

Time frame:
C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.
Reported as:
Geometric mean · Liter/day
CL/F (L/Day)
Liter/dayCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
CL/F (L/Day)0.61 ± 510.53 ± 310.46 ± 340.44 ± 38
SecondaryV1/F (L)

Apparent volume of distribution of the central compartment

Time frame:
C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.
Reported as:
Geometric mean · Liter
V1/F (L)
LiterCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
V1/F (L)11.65 ± 5310.15 ± 3111.36 ± 3410.84 ± 39
SecondaryKa (Day-1)

First-order rate constant of absorption

Time frame:
C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.
Reported as:
Geometric mean · Day-1
Ka (Day-1)
Day-1Cohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Ka (Day-1)0.3 ± 370.28 ± 190.29 ± 210.28 ± 28
SecondaryT1/2 (Day)

Elimination half-life

Time frame:
C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.
Reported as:
Geometric mean · Day
T1/2 (Day)
DayCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
T1/2 (Day)13.28 ± 2.413.3 ± 1.416.96 ± 2.116.98 ± 2.2
SecondaryTmax (Day)

Time to reach the maximum concentration for the first dose (Cmax)

Time frame:
C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.
Reported as:
Median · Day
Tmax (Day)
DayCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Tmax (Day)6.72 (4.84 to 10.01)7.38 (5.75 to 9.14)7.85 (6.17 to 9.54)7.96 (5.24 to 11.34)
SecondaryCmax (µg/mL)

Maximum concentration for the first dose

Time frame:
C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.
Reported as:
Geometric mean · µg/mL
Cmax (µg/mL)
µg/mLCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Cmax (µg/mL)4.41 ± 394.68 ± 204.96 ± 235.01 ± 30
SecondaryCmax.ss (µg/mL)

Maximum concentration for the first dose (Cmax) at steady state for the starting dose

Time frame:
C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.
Reported as:
Geometric mean · µg/mL
Cmax.ss (µg/mL)
µg/mLCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Cmax.ss (µg/mL)7.28 ± 427.72 ± 219.45 ± 249.6 ± 32
SecondaryAUCss (Day* µg/mL)

Area under the concentration-time curve at the steady state for the starting dose

Time frame:
C1D1 (pre-dose), C1D8, C1D15, C2D1, C4D1, C5D1, C5D8, C6D1, and C8D1, day 169, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.
Reported as:
Geometric mean · day* µg/mL
AUCss (Day* µg/mL)
day* µg/mLCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
AUCss (Day* µg/mL)123 ± 47132 ± 24168 ± 26171 ± 35
SecondaryThe Number of Participants With Antidrug Antibody (ADA) Measurements

The ADA status of a participant during treatment is determined based on the longitudinal ADA results as follows: Negative: All samples (baseline and post-baseline) are negative. Positive to treatment-emergent ADA: At least one post-baseline sample is positive if the baseline sample is negative, or at least one post-baseline sample is positive with a titer ≥ 4-fold of the baseline titer if the baseline sample is positive

Time frame:
C1D1 (pre- dose), C2D1, C4D1, C6D1, C8D1, Day 1 of every 4th Extension Phase treatment cycle for up to 1 year post the date of first dose of luspatercept, and end of treatment.
Reported as:
Count of participants · Participants
The Number of Participants With Antidrug Antibody (ADA) Measurements
ParticipantsCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Positive1222
Negative21191236
SecondaryMean Changes in Hemoglobin Over the Study Compared to Baseline in the Absence of RBC Transfusions (Cohorts 1 and 3A)

Calculated based on average hemoglobin measurements collected during the treatment period.The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. The baseline RBC transfusion is defined as average number of RBC units/28 days over the 84 days period immediately prior to the C1D1 date.

Time frame:
Baseline and Day 1 through end of treatment (up to approximately 232 weeks)
Reported as:
Mean · g/dL
Mean Changes in Hemoglobin Over the Study Compared to Baseline in the Absence of RBC Transfusions (Cohorts 1 and 3A)
g/dLCohort 1: Anemia OnlyCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)
Primary Treatment Period0.795 ± 0.76971.157 ± 0.5178
Entire Treatment Period0.824 ± 0.86131.172 ± 0.5992
SecondaryThe Number of Participants With a Mean Hemoglobin Increase >= 1.5 g/dL From Baseline Over Any Consecutive 84-day Period (Cohorts 1 and 3A)

The number of participants with a Mean hemoglobin increase of ≥ 1.5 g/dL from baseline over any consecutive 84-day period without an RBC transfusion. The primary treatment period is from Day 1 to and including Day 168. The entire treatment period is from Day 1 through the end of treatment. Baseline is defined as all non-missing Hgb records within 28 days on or prior to date of first dose (or date of enrollment if not treated).

Time frame:
Baseline and Day 1 through end of treatment (up to approximately 232 weeks)
Reported as:
Count of participants · Participants
The Number of Participants With a Mean Hemoglobin Increase >= 1.5 g/dL From Baseline Over Any Consecutive 84-day Period (Cohorts 1 and 3A)
ParticipantsCohort 1: Anemia OnlyCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)
Primary Treatment Period56
Entire Treatment Period67

Adverse events

Collected over Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 4 years and 8 months) SAEs and Other AEs were assessed from first dose through 42 days after the last dose (up to approximately 238 weeks). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort 1: Anemia Only6/22 (27.3%)8/22 (36.4%)21/22 (95.5%)
Cohort 2: RBC-Transfusion Dependent12/21 (57.1%)8/21 (38.1%)19/21 (90.5%)
Cohort 3A: Anemia Only (Stable Dose of Ruxolitinib)2/14 (14.3%)4/14 (28.6%)13/14 (92.9%)
Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)13/38 (34.2%)17/38 (44.7%)33/38 (86.8%)
Most frequent serious events
Showing 10 of 63
Most frequent serious events
EventCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/220/212/142/38
AnaemiaBlood and lymphatic system disorders0/222/210/140/38
SyncopeNervous system disorders0/222/210/141/38
Urinary tract infectionInfections and infestations2/221/210/140/38
AstheniaGeneral disorders0/220/211/140/38
InfluenzaInfections and infestations1/220/211/140/38
UrosepsisInfections and infestations0/220/211/140/38
Pulmonary embolismRespiratory, thoracic and mediastinal disorders0/220/211/140/38
DiarrhoeaGastrointestinal disorders0/221/210/141/38
FatigueGeneral disorders0/221/210/140/38
Most frequent other events
Showing 10 of 93
Most frequent other events
EventCohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)
HypertensionVascular disorders5/223/216/149/38
ThrombocytopeniaBlood and lymphatic system disorders3/223/211/1411/38
DiarrhoeaGastrointestinal disorders3/224/214/1411/38
FatigueGeneral disorders4/225/212/146/38
CoughRespiratory, thoracic and mediastinal disorders3/225/210/144/38
DyspnoeaRespiratory, thoracic and mediastinal disorders4/225/212/149/38
Abdominal painGastrointestinal disorders5/222/212/144/38
PyrexiaGeneral disorders5/221/211/147/38
Influenza like illnessGeneral disorders1/221/213/141/38
ArthralgiaMusculoskeletal and connective tissue disorders2/220/213/146/38

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Cohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)Total
Mean69 ± 8.8773.9 ± 5.7165.4 ± 8.4571.3 ± 5.8070.5 ± 7.42
Sex: Female, Male
Sex: Female, Male(Participants)Cohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)Total
Female9671537
Male131572358
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)Total
Hispanic or Latino20013
Not Hispanic or Latino1619143281
Unknown or Not Reported420511
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort 1: Anemia OnlyCohort 2: RBC-Transfusion DependentCohort 3A: Anemia Only (Stable Dose of Ruxolitinib)Cohort 3B: RBC-Transfusion Dependent (Stable Dose of Ruxolitinib)Total
American Indian or Alaska Native00000
Asian21317
Native Hawaiian or Other Pacific Islander00000
Black or African American00123
White1618103074
More than one race00000
Unknown or Not Reported420511
08

Study locations

47 sites
  • Local Institution - 102
    Phoenix, Arizona 85054, United States
  • Mayo Clinic - Arizona
    Phoenix, Arizona 85054, United States
  • Local Institution - 103
    Stanford, California 94305, United States
  • Stanford Cancer Center
    Stanford, California 94305, United States
  • Local Institution - 101
    Jacksonville, Florida 32224, United States
  • Mayo Clinic - Jacksonville
    Jacksonville, Florida 32224, United States
  • Local Institution - 107
    Orange City, Florida 32763, United States
  • Mid Florida Hematology and Oncology Centers, PA
    Orange City, Florida 32763, United States
  • H. Lee Moffitt Cancer Center and Research Institute
    Tampa, Florida 33612, United States
  • Local Institution - 108
    Tampa, Florida 33612, United States
  • Local Institution - 104
    New York, New York 10029, United States
  • Mount Sinai Medical Center
    New York, New York 10029, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • Local Institution - 109
    Cleveland, Ohio 44195, United States
  • Avera Research Institute
    Sioux Falls, South Dakota 57105, United States
  • Local Institution - 105
    Sioux Falls, South Dakota 57105, United States
  • Local Institution - 100
    Houston, Texas 77030, United States
  • MD Anderson Cancer Center The University of Texas
    Houston, Texas 77030, United States
  • Local Institution - 106
    San Antonio, Texas 78229, United States
  • University of Texas Health Science Center at San Antonio
    San Antonio, Texas 78229, United States
  • CHRU de Brest - Hopital Morvan
    Brest, 29609, France
  • Local Institution - 203
    Brest, 29609, France
  • Centre Hospitalier de Lens
    Lens, 62307, France
  • Local Institution - 201
    Lens, 62307, France
  • Hopital Saint Louis
    Paris, 75010, France
  • Local Institution - 200
    Paris, 75010, France
  • Gustave Roussy
    Villejuif, 94805, France
  • Local Institution - 202
    Villejuif, 94805, France
  • Azienda Ospedaliera Papa Giovanni XXIII
    Bergamo, 24127, Italy
  • Local Institution - 304
    Bergamo, 24127, Italy
  • Azienda Ospedaliera Universitaria Careggi
    Florence, 50134, Italy
  • Local Institution - 300
    Florence, 50134, Italy
  • Fondazione IRCCS Policlinico San Matteo
    Pavia, 27100, Italy
  • Local Institution - 301
    Pavia, 27100, Italy
  • Istituto Clinico Humanitas
    Rozzano (MI), 20089, Italy
  • Local Institution - 303
    Rozzano (MI), 20089, Italy
  • Local Institution - 302
    Varese, 21100, Italy
  • Ospedale di Circolo di Varese
    Varese, 21100, Italy
  • Belfast Health and Social Care Trust
    Belfast Northern Ireland, BT9 7AB, United Kingdom
  • Local Institution - 404
    Cardiff, CF14 4XW, United Kingdom
  • University Hospital of Wales
    Cardiff, CF14 4XW, United Kingdom
  • Local Institution - 400
    Headington, Oxford, OX3 7LE, United Kingdom
  • University of Oxford
    Headington, Oxford, OX3 7LE, United Kingdom
  • Guy's and St Thomas' NHS Foundation Trust - Guy's Hospital
    London, SE1 9RT, United Kingdom
  • Local Institution - 403
    London, SE1 9RT, United Kingdom
  • Imperial College London
    London, W12 0HS, United Kingdom
  • Local Institution - 402
    London, W12 0HS, United Kingdom
09

References and documents

Publications

  • Gerds AT, Harrison C, Kiladjian JJ, Mesa R, Vannucchi AM, Komrokji R, Bose P, Kremyanskaya M, Mead AJ, Gotlib J, Rose S, Sanabria F, Marsousi N, Giuseppi AC, Jiang H, Palmer JM, McCaul K, Ribrag V, Passamonti F. Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis. Blood Adv. 2024 Sep 10;8(17):4511-4522. doi: 10.1182/bloodadvances.2024012939. PubMed 38820422 ↗

Study documents

  • Protocol and statistical analysis plan · Feb 19, 2020

Documents are hosted by the registry — open the source record to download them.

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Nov 2017 to primary completion in Jul 2022, 56 months.

Results were first posted in Aug 2023, 1 year 1 month after primary completion.

Of 30 industry-sponsored phase 2 interventional studies under Primary Myelofibrosis, half reached primary completion within 32 months of starting (the median), counting those still running; a quarter within 25 and three quarters within 66. This study's 56 months is above that.

Counting every sponsor, half of 90 studies reached it within 66 months; a quarter within 32 and three quarters within 111.

How these figures are worked out, and which studies are left out of them.

Registered
Jun 15, 2017
First posted
Jun 21, 2017
StartActual
Nov 15, 2017
Primary completionActual
Jul 18, 2022
CompletionActual
Jul 18, 2022
Results first posted
Aug 24, 2023
Last update
Aug 24, 2023
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Aug 24, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03194542
Lead sponsor
Celgene
Responsible party
Sponsor
First posted
Jun 21, 2017
Start date
Nov 15, 2017
Primary completion
Jul 18, 2022
Completion
Jul 18, 2022
Results posted
Aug 24, 2023
Last update
Aug 24, 2023

Study contacts

Bristol-Myers Squibb
study director · Bristol-Myers Squibb

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Aug 2023. You cannot join it, but the record below documents what was studied.

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Studies of the drug tested here: Luspatercept

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