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TerminatedNCT04103645Updated Jul 2, 2025Results posted

Intra-patient Dose Escalation Study to Investigate Safety and Feasibility of Vactosertib in Treating Anemic MPN Patients

A Phase 2 interventional study of Vactosertib and Vactosertib in Myeloproliferative Neoplasm, sponsored by Weill Medical College of Cornell University. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-07-02.

Sponsored by Weill Medical College of Cornell University · Phase 2, Interventional, and Treatment

Why this study was terminated
Low accrual
Phase
Phase 2
Study type
Interventional
Enrollment
2
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

This study assesses the potential of using a TGFβ receptor inhibitor for the treatment of anemic patients with myeloproliferative neoplasms. TGFβ signaling is known to be abnormally high in patients with myeloproliferative neoplasms and it is thought that abnormal TGFβ signals cause many of the problems with blood cell formation in these diseases. The study design allows all patients to receive the study drug, vactosertib. The dose of vactosertib is individualized within a pre-set range based upon its effectiveness and tolerability. A total of up to 37 patients will be treated.

Read the detailed description

This is a two-tiered multi arm Phase 2 trial of vactosertib (TEW-7197) for the treatment of anemia in Ph-neg MPNs. Both tiers use a rule-based, accelerated dose escalation scheme to efficiently assess the potential of vactosertib to safely and effectively treat anemic patients with Ph-neg MPNs. The first tier of this trial (Tier 1) is an intra-patient dose finding study in 12 patients that uses a low starting dose of vactosertib for all patients. Treatment dose is escalated according to prospectively-defined rules, and a toxicity and treatment effect algorithm during the period of 16 weeks (4 treatment cycles). If pre-established efficacy and safety endpoints are met, then Tier 1 of the study will be followed by a Tier 2 expansion study with an additional 25 patients for a period of 24 weeks (6 treatment cycles).

Vactosertib will be administered concurrently with the patient's current treatment (if any). Prior to enrollment, patients must be on a stable dose of their current therapy for 3 months prior to entering the study. Supportive care measures including packed red blood cell (PRBC) transfusions for HGB \<7g/dL, or symptomatic anemia, will be permitted. Administration of erythropoiesis stimulating agents (ESAs), however, will not be permitted on the trial (patients recruited would have serum EPO >125 U/L above which the benefit of ESAs is not supported).

02

Conditions studied

  • Myeloproliferative Neoplasm

Keywords

  • Anemia
03

In context

Myeloproliferative Disorders

626 studies on the registry are indexed under Myeloproliferative Disorders; 109 are open to participants now.

This study's enrollment of 2 is below the median of 45 across 439 interventional studies indexed under Myeloproliferative Disorders.

Browse Myeloproliferative Disorders studies →

Lead sponsor

Weill Medical College of Cornell University is the lead sponsor of 867 studies on the registry; 160 are open to participants now.

Of its 119 completed or terminated interventional studies of FDA-regulated products, 91 (76%) have results posted.

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

Inclusion criteria

Patients who meet the WHO 2016 criteria for a Ph-neg MPN (including PV, ET, MF, MDS/MPN, MPN-U).

  • Patients with MF must have DIPSS+ Intermediate or High-risk MF (primary of post-PV/ET).
  • For patients receiving cytoreductive therapy, they should be on a stable dose of current cytoreductive therapy for at least 3 months prior to C1D1.
  • Anemia as defined by HGB \< 10 g/dL, or transfusion of ≥ 2 packed red blood cell (PRBC) unit within the past 4 weeks with HGB ≤8.5g/dL.

  • Ineligible, unsuitable or refractoriness to ESA therapy defined as any of the following:

    • Serum erythropoietin (EPO) >125 U/L.
    • Proven ESA unsuitability is defined by history of any of the following:
    • Loss of erythroid hematologic improvement while receiving stable or increased ESA dose; or
    • ESA-attributed toxicity that, in the treating physician's opinion, makes ESA therapy unsuitable for subject.
    • ESA refractoriness defined by lack of erythroid hematologic improvement to ESA:27
    • Less than 1.5 g/dL increase in hemoglobin after at least 6 weeks of ESA therapy; or
    • Ongoing transfusion dependence that has not been reduced by > 4U over an 8-week period compared to ESA pre-treatment 8 weeks.
  • Acceptable Cardiovascular status

Exclusion criteria

Exclusion Criteria:

  • Any other serious medical condition which in the Investigator's opinion would preclude safe participation in the study.
  • Patients with history of TIA or stroke within the past 12 months are excluded.
  • Female subjects who are breastfeeding, or intend to breastfeed, during the study or in the 30 days following the last dose of study drug are excluded.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
2 participants (actual)

Study arms

  • Experimental
    Tier 1: Vactosertib 50 mg BID

    Vactosertib intra-patient dose finding cohort.

    Drug: Vactosertib

  • Experimental
    Tier 1: Vactosertib 100 mg BID

    Drug: Vactosertib

  • Experimental
    Tier 1: Vactosertib 150 mg BID

    Drug: Vactosertib

  • Experimental
    Tier 1: Vactosertib 200mg BID

    Drug: Vactosertib

  • Experimental
    Tier 2: Vactosertib

    Drug: Vactosertib

Interventions

  • DrugVactosertib

    50 mg BID This drug is a TGF-Beta receptor type 1 inhibitor, by inhibiting phosphorylation of the ALK5 substrates SMAD2 and SMAD3. This inhibition could promote regeneration of normal human stem cells and proliferation of erythroid progenitors to treat the underlying hypoproliferative anemia in advanced MPNs.

    Also known as: TEW-7197

  • DrugVactosertib

    100 mg BID This drug is a TGF-Beta receptor type 1 inhibitor, by inhibiting phosphorylation of the ALK5 substrates SMAD2 and SMAD3. This inhibition could promote regeneration of normal human stem cells and proliferation of erythroid progenitors to treat the underlying hypoproliferative anemia in advanced MPNs.

    Also known as: TEW-7197

  • DrugVactosertib

    150 mg BID This drug is a TGF-Beta receptor type 1 inhibitor, by inhibiting phosphorylation of the ALK5 substrates SMAD2 and SMAD3. This inhibition could promote regeneration of normal human stem cells and proliferation of erythroid progenitors to treat the underlying hypoproliferative anemia in advanced MPNs.

    Also known as: TEW-7197

  • DrugVactosertib

    200 mg BID This drug is a TGF-Beta receptor type 1 inhibitor, by inhibiting phosphorylation of the ALK5 substrates SMAD2 and SMAD3. This inhibition could promote regeneration of normal human stem cells and proliferation of erythroid progenitors to treat the underlying hypoproliferative anemia in advanced MPNs.

    Also known as: TEW-7197

  • DrugVactosertib

    The lowest dose level of vactosertib for which no DLT was observed in Tier 1 AND The lowest dose level for which at least one of the 12 subjects enrolled on Tier 1 met Criteria for Clinical Benefit. Or, if a single dose level does not fulfil both Criterion 1 and Criterion 2, the starting dose level for Tier 2 will lowest dose from Tier 1 for which no DLT was identified.

    Also known as: TEW-7197

06

What researchers measure

Primary outcomes

  1. Identify the Safest, Minimally Effective Starting Dose Level for Patients on Tier 1

    The safest minimally effective dose is defined as the lowest dose level for which no dose limiting toxicity (DLT) was observed in Tier 1 AND the lowest dose level for which at least one of the 12 subjects enrolled on Tier 1 meet Criteria for Clinical Benefit

    Time frame: Baseline to week 16

  2. Identify Dose Limiting Toxicities (DLTs) in Patients With MPN Enrolled on Tier 1

    Identify the incidence of dose limiting toxicity (DLT) within the first 12 weeks which are defined as: 1. Any non-hematologic grade ≥3 toxicity except for nausea, vomiting or diarrhea lasting 3 days or less 2. Any grade 4 neutropenia of any duration 3. Any grade ≥3 neutropenia that has not recovered to grade ≥2 within 7 days of onset 4. Any grade ≥3 febrile neutropenia 5. Any grade ≥3 thrombocytopenia associated with clinically significant bleeding or requiring platelet transfusion

    Time frame: Baseline to week 12

  3. Identify the Maximum Tolerated Dose (MTD) of Vactosertib in Patients With MPN Enrolled on Tier 1

    Identify the Maximum Tolerated Dose (MTD) of vactosertib defined as the highest dose which does not meet the Tier 1 stopping rule. The tier 1 stopping rule is triggered if any patient experiences a Grade 5 dose limiting toxicity within the first 12 weeks of starting vactosertib or if more than five patients experience a dose limiting toxicity at any dose within the first 12 weeks on study.

    Time frame: Baseline to week 12

  4. Number of Tier 2 Patients Who Have Achieved Erythropoietic Response as Defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria

    Number of patients who achieve an erythropoietic response defined by: 1. HGB increase of 1.5g/dL compared to baseline hemoglobin; 2. Reduction in PRBC transfusion rate to ≤ 50% of pre-treatment transfusion rate; or 3. Reduction in PRBC transfusions by ≥ 4 Units over an 8-week period.

    Time frame: baseline to week 16

  5. Number of Tier 2 Patients Who Have Achieved Clinical Response in Symptoms as Defined by International Working Group (IWG) Criteria

    Number of patients who have achieved clinical response defined by a reduction in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) total score by ≥ 50% compared to pretreatment score

    Time frame: baseline to week 16

  6. Number of Tier 2 Patients Who Have Achieved Splenic Response in Symptoms as Defined by International Working Group (IWG) Criteria

    Number of patients who have achieved splenic response defined by: 1. Non-palpable spleen when baseline spleen size was 5-10 cm below left costal margin; 2. At least 50% reduction in spleen size when baseline spleen is \> 10 cm below left costal margin 3. At least 35% reduction in spleen size as assessed by US, CT or MRI.

    Time frame: baseline to week 16

  7. Identify Dose Limiting Toxicities (DLTs) in Patients With MPN Enrolled on Tier 2

    Identify the number of dose limiting toxicities (DLT) within the first 12 weeks which are defined as: 1. Any non-hematologic grade ≥3 toxicity except for nausea, vomiting or diarrhea lasting 3 days or less 2. Any grade 4 neutropenia of any duration 3. Any grade ≥3 neutropenia that has not recovered to grade ≥2 within 7 days of onset 4. Any grade ≥3 febrile neutropenia 5. Any grade ≥3 thrombocytopenia associated with clinically significant bleeding or requiring platelet transfusion

    Time frame: baseline to week 12

  8. Identify the Maximum Tolerated Dose (MTD) of Vactosertib in Patients With MPN Enrolled on Tier 2

    Identify the Maximum Tolerated Dose (MTD) of vactosertib defined as the highest dose which does not meet the Tier 2 stopping rule. The tier 2 stopping rule is triggered if any patient experiences a Grade 5 dose limiting toxicity within the first 12 weeks of starting vactosertib or if more than five patients experience a dose limiting toxicity at any dose within the first 12 weeks on study.

    Time frame: baseline to week 12

Secondary outcomes

  1. Number of Patients in Which a Histological Response is Seen

    Histological response is defined by reduction of any amount in grade of bone marrow fibrosis by histopathologic assessment at 16 weeks.

    Time frame: 16 weeks

  2. Number of Patients in Which a Molecular Response is Seen

    Number of patients in which a molecular response is seen. Molecular response is defined by a decrease in VAF of MPN-driver mutations (eg. JAK2, CALR, and MPL allelic ratio) in blood and/or bone marrow cells

    Time frame: 16 weeks

  3. Number of Patients in Which a Pharmacodynamic Response is Seen

    A pharmacodynamic response is defined as any of the following: 1. Reduced immunohistochemical staining for SMAD2/3 phosphorylation in bone marrow biopsy sections. 2. Reduced mean fluorescence intensity of SMAD2/3 phosphorylation staining in peripheral blood hematopoietic stem and progenitor cells (HSPCs) or mature progeny as assessed by flow cytometry. 3. Reduced mean fluorescence intensity of SMAD2/3 phosphorylation staining in bone marrow hematopoietic stem and progenitor cells (HSPCs) or mature progeny as assessed by flow cytometry.

    Time frame: 16 weeks

  4. Number of Patients Who Have Experienced Any of the Following: Hematologic Toxicities, Infections, Disease Progression, and Thrombosis Events

    Time frame: baseline to 16 weeks

  5. Overall Survival Defined as the Amount of Time a Patient is Alive After Starting Study Treatment

    The overall survival range describes the average length of time subjects were followed for survival

    Time frame: Week 1 Day 1 to 6 months post treatment discontinuation. This collection period for both subjects on study was over an average duration of 54 weeks.

  6. Progression Free Survival Defined as the Duration of Time From Start of Treatment to Time of Progression

    Time frame: Week 1 Day 1 to 6 months post treatment discontinuation

07

Results

Posted Jul 2, 2025
Limitations and caveats
Only a small number of subjects was analyzed due to low accrual and early termination. Additionally, only Tier 1 outcome measures could be analyzed due to 0 subjects enrolling onto Tier 2.

Participant flow

Vactosertib 50 mg BID (Tier 1)
Participant flow — Vactosertib 50 mg BID (Tier 1)
MilestoneVacosertib 50 mg BIDVacosertib 100 mg BIDVacosertib 150 mg BIDVacosertib 200mg BIDTier 2: Vactosertib
Started20000
Completed20000
Not completed00000
Vactosertib 100 mg BID (Tier 1)
Participant flow — Vactosertib 100 mg BID (Tier 1)
MilestoneVacosertib 50 mg BIDVacosertib 100 mg BIDVacosertib 150 mg BIDVacosertib 200mg BIDTier 2: Vactosertib
Started02000
Completed02000
Not completed00000
Vactosertib 150 mg BID (Tier 1)
Participant flow — Vactosertib 150 mg BID (Tier 1)
MilestoneVacosertib 50 mg BIDVacosertib 100 mg BIDVacosertib 150 mg BIDVacosertib 200mg BIDTier 2: Vactosertib
Started00200
Completed00200
Not completed00000
Vactosertib 200 mg BID (Tier 1)
Participant flow — Vactosertib 200 mg BID (Tier 1)
MilestoneVacosertib 50 mg BIDVacosertib 100 mg BIDVacosertib 150 mg BIDVacosertib 200mg BIDTier 2: Vactosertib
Started00020
Completed00020
Not completed00000
Vactosertib (Tier 2)
Participant flow — Vactosertib (Tier 2)
MilestoneVacosertib 50 mg BIDVacosertib 100 mg BIDVacosertib 150 mg BIDVacosertib 200mg BIDTier 2: Vactosertib
Started00000
Completed00000
Not completed00000

Outcome measures

PrimaryIdentify the Safest, Minimally Effective Starting Dose Level for Patients on Tier 1

The safest minimally effective dose is defined as the lowest dose level for which no dose limiting toxicity (DLT) was observed in Tier 1 AND the lowest dose level for which at least one of the 12 subjects enrolled on Tier 1 meet Criteria for Clinical Benefit

Time frame:
Baseline to week 16
Reported as:
Number · mg
Identify the Safest, Minimally Effective Starting Dose Level for Patients on Tier 1
mgAll Participants
Identify the Safest, Minimally Effective Starting Dose Level for Patients on Tier 150
PrimaryIdentify Dose Limiting Toxicities (DLTs) in Patients With MPN Enrolled on Tier 1

Identify the incidence of dose limiting toxicity (DLT) within the first 12 weeks which are defined as: 1. Any non-hematologic grade ≥3 toxicity except for nausea, vomiting or diarrhea lasting 3 days or less 2. Any grade 4 neutropenia of any duration 3. Any grade ≥3 neutropenia that has not recovered to grade ≥2 within 7 days of onset 4. Any grade ≥3 febrile neutropenia 5. Any grade ≥3 thrombocytopenia associated with clinically significant bleeding or requiring platelet transfusion

Time frame:
Baseline to week 12
Reported as:
Number · Count of DLTs
Identify Dose Limiting Toxicities (DLTs) in Patients With MPN Enrolled on Tier 1
Count of DLTsTier 1: Vactosertib 50 mg BIDTier 1: Vactosertib 100 mg BIDTier 1: Vactosertib 150 mg BIDTier 1: Vactosertib 200mg BID
Identify Dose Limiting Toxicities (DLTs) in Patients With MPN Enrolled on Tier 10000
PrimaryIdentify the Maximum Tolerated Dose (MTD) of Vactosertib in Patients With MPN Enrolled on Tier 1

Identify the Maximum Tolerated Dose (MTD) of vactosertib defined as the highest dose which does not meet the Tier 1 stopping rule. The tier 1 stopping rule is triggered if any patient experiences a Grade 5 dose limiting toxicity within the first 12 weeks of starting vactosertib or if more than five patients experience a dose limiting toxicity at any dose within the first 12 weeks on study.

Time frame:
Baseline to week 12
Reported as:
Number · mg
Identify the Maximum Tolerated Dose (MTD) of Vactosertib in Patients With MPN Enrolled on Tier 1
mgAll Participants
Identify the Maximum Tolerated Dose (MTD) of Vactosertib in Patients With MPN Enrolled on Tier 1200
PrimaryNumber of Tier 2 Patients Who Have Achieved Erythropoietic Response as Defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) Criteria

Number of patients who achieve an erythropoietic response defined by: 1. HGB increase of 1.5g/dL compared to baseline hemoglobin; 2. Reduction in PRBC transfusion rate to ≤ 50% of pre-treatment transfusion rate; or 3. Reduction in PRBC transfusions by ≥ 4 Units over an 8-week period.

Time frame:
baseline to week 16

No measurements were reported for this outcome.

PrimaryNumber of Tier 2 Patients Who Have Achieved Clinical Response in Symptoms as Defined by International Working Group (IWG) Criteria

Number of patients who have achieved clinical response defined by a reduction in Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) total score by ≥ 50% compared to pretreatment score

Time frame:
baseline to week 16

No measurements were reported for this outcome.

PrimaryNumber of Tier 2 Patients Who Have Achieved Splenic Response in Symptoms as Defined by International Working Group (IWG) Criteria

Number of patients who have achieved splenic response defined by: 1. Non-palpable spleen when baseline spleen size was 5-10 cm below left costal margin; 2. At least 50% reduction in spleen size when baseline spleen is \> 10 cm below left costal margin 3. At least 35% reduction in spleen size as assessed by US, CT or MRI.

Time frame:
baseline to week 16

No measurements were reported for this outcome.

PrimaryIdentify Dose Limiting Toxicities (DLTs) in Patients With MPN Enrolled on Tier 2

Identify the number of dose limiting toxicities (DLT) within the first 12 weeks which are defined as: 1. Any non-hematologic grade ≥3 toxicity except for nausea, vomiting or diarrhea lasting 3 days or less 2. Any grade 4 neutropenia of any duration 3. Any grade ≥3 neutropenia that has not recovered to grade ≥2 within 7 days of onset 4. Any grade ≥3 febrile neutropenia 5. Any grade ≥3 thrombocytopenia associated with clinically significant bleeding or requiring platelet transfusion

Time frame:
baseline to week 12

No measurements were reported for this outcome.

PrimaryIdentify the Maximum Tolerated Dose (MTD) of Vactosertib in Patients With MPN Enrolled on Tier 2

Identify the Maximum Tolerated Dose (MTD) of vactosertib defined as the highest dose which does not meet the Tier 2 stopping rule. The tier 2 stopping rule is triggered if any patient experiences a Grade 5 dose limiting toxicity within the first 12 weeks of starting vactosertib or if more than five patients experience a dose limiting toxicity at any dose within the first 12 weeks on study.

Time frame:
baseline to week 12

No measurements were reported for this outcome.

SecondaryNumber of Patients in Which a Histological Response is Seen

Histological response is defined by reduction of any amount in grade of bone marrow fibrosis by histopathologic assessment at 16 weeks.

Time frame:
16 weeks
Reported as:
Count of participants · Participants
Number of Patients in Which a Histological Response is Seen
ParticipantsTier 1: Vactosertib 50 mg BIDTier 1: Vactosertib 100 mg BIDTier 1: Vactosertib 150 mg BIDTier 1: Vactosertib 200mg BIDTier 2: Vactosertib
Number of Patients in Which a Histological Response is Seen00000
SecondaryNumber of Patients in Which a Molecular Response is Seen

Number of patients in which a molecular response is seen. Molecular response is defined by a decrease in VAF of MPN-driver mutations (eg. JAK2, CALR, and MPL allelic ratio) in blood and/or bone marrow cells

Time frame:
16 weeks
Reported as:
Count of participants · Participants
Number of Patients in Which a Molecular Response is Seen
ParticipantsTier 1: Vactosertib 50 mg BIDTier 1: Vactosertib 100 mg BIDTier 1: Vactosertib 150 mg BIDTier 1: Vactosertib 200mg BIDTier 2: Vactosertib
Number of Patients in Which a Molecular Response is Seen00010
SecondaryNumber of Patients in Which a Pharmacodynamic Response is Seen

A pharmacodynamic response is defined as any of the following: 1. Reduced immunohistochemical staining for SMAD2/3 phosphorylation in bone marrow biopsy sections. 2. Reduced mean fluorescence intensity of SMAD2/3 phosphorylation staining in peripheral blood hematopoietic stem and progenitor cells (HSPCs) or mature progeny as assessed by flow cytometry. 3. Reduced mean fluorescence intensity of SMAD2/3 phosphorylation staining in bone marrow hematopoietic stem and progenitor cells (HSPCs) or mature progeny as assessed by flow cytometry.

Time frame:
16 weeks
Reported as:
Count of participants · Participants
Number of Patients in Which a Pharmacodynamic Response is Seen
ParticipantsTier 1: Vactosertib 50 mg BIDTier 1: Vactosertib 100 mg BIDTier 1: Vactosertib 150 mg BIDTier 1: Vactosertib 200mg BIDTier 2: Vactosertib
Number of Patients in Which a Pharmacodynamic Response is Seen00010
SecondaryNumber of Patients Who Have Experienced Any of the Following: Hematologic Toxicities, Infections, Disease Progression, and Thrombosis Events
Time frame:
baseline to 16 weeks
Reported as:
Count of participants · Participants
Number of Patients Who Have Experienced Any of the Following: Hematologic Toxicities, Infections, Disease Progression, and Thrombosis Events
ParticipantsTier 1: Vactosertib 50 mg BIDTier 1: Vactosertib 100 mg BIDTier 1: Vactosertib 150 mg BIDTier 1: Vactosertib 200 mg BIDTier 2: Vactosertib
Number of Patients Who Have Experienced Any of the Following: Hematologic Toxicities, Infections, Disease Progression, and Thrombosis Events00120
SecondaryOverall Survival Defined as the Amount of Time a Patient is Alive After Starting Study Treatment

The overall survival range describes the average length of time subjects were followed for survival

Time frame:
Week 1 Day 1 to 6 months post treatment discontinuation. This collection period for both subjects on study was over an average duration of 54 weeks.
Reported as:
Mean · Weeks
Overall Survival Defined as the Amount of Time a Patient is Alive After Starting Study Treatment
WeeksAll Participants
Overall Survival Defined as the Amount of Time a Patient is Alive After Starting Study Treatment54 (54 to 54)
SecondaryProgression Free Survival Defined as the Duration of Time From Start of Treatment to Time of Progression
Time frame:
Week 1 Day 1 to 6 months post treatment discontinuation
Reported as:
Mean · Weeks
Progression Free Survival Defined as the Duration of Time From Start of Treatment to Time of Progression
WeeksAll Participants
Progression Free Survival Defined as the Duration of Time From Start of Treatment to Time of Progression25.5 (21 to 30)

Adverse events

Collected over Deaths were collected from Week 1 Day 1 through 6 months post treatment discontinuation. This collection period for both subjects on study was over an average duration of 54 weeks. Serious and Other (Not Including Serious) Adverse Events were collected while subjects were on treatment. This collection period for both subjects on study was over an average duration of 28 weeks.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Tier 1: Vactosertib 50 mg BID0/2 (0%)0/2 (0%)2/2 (100%)
Tier 1: Vactosertib 100 mg BID0/2 (0%)0/2 (0%)2/2 (100%)
Tier 1: Vactosertib 150 mg BID0/2 (0%)0/2 (0%)2/2 (100%)
Tier 1: Vactosertib 200mg BID0/2 (0%)0/2 (0%)2/2 (100%)
Tier 2: Vactosertib———
All Participants0/2 (0%)0/2 (0%)2/2 (100%)
Most frequent other events
Showing 10 of 23
Most frequent other events
EventTier 1: Vactosertib 50 mg BIDTier 1: Vactosertib 100 mg BIDTier 1: Vactosertib 150 mg BIDTier 1: Vactosertib 200mg BIDTier 2: VactosertibAll Participants
FatigueGeneral disorders0/20/20/22/2—2/2
Decreased AppetiteMetabolism and nutrition disorders1/21/20/20/2—1/2
DepressionPsychiatric disorders0/20/20/21/2—1/2
ConstipationGastrointestinal disorders0/20/21/21/2—1/2
DiarrheaGastrointestinal disorders0/20/20/21/2—1/2
Abdominal distensionGastrointestinal disorders0/20/20/21/2—1/2
VertigoEar and labyrinth disorders0/20/20/21/2—1/2
ParesthesiaNervous system disorders0/20/20/21/2—1/2
Pain extremity (left lower leg)Musculoskeletal and connective tissue disorders0/20/20/21/2—1/2
Aspartate aminotransferase increasedInvestigations0/20/20/21/2—1/2

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)All Participants
<=18 years0
Between 18 and 65 years0
>=65 years2
Sex: Female, Male
Sex: Female, Male(Participants)All Participants
Female1
Male1
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)All Participants
Hispanic or Latino0
Not Hispanic or Latino2
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)All Participants
American Indian or Alaska Native0
Asian1
Native Hawaiian or Other Pacific Islander0
Black or African American0
White1
More than one race0
Unknown or Not Reported0
08

Study locations

1 site
  • Weill Medical College of Cornell University
    New York, New York 10021, United States
09

References and documents

Publications

  • Hernandez-Boluda JC, Correa JG, Garcia-Delgado R, Martinez-Lopez J, Alvarez-Larran A, Fox ML, Garcia-Gutierrez V, Perez-Encinas M, Ferrer-Marin F, Mata-Vazquez MI, Raya JM, Estrada N, Garcia S, Kerguelen A, Duran MA, Albors M, Cervantes F. Predictive factors for anemia response to erythropoiesis-stimulating agents in myelofibrosis. Eur J Haematol. 2017 Apr;98(4):407-414. doi: 10.1111/ejh.12846. Epub 2017 Jan 19. PubMed 28009442 ↗
  • Tefferi A, Cervantes F, Mesa R, Passamonti F, Verstovsek S, Vannucchi AM, Gotlib J, Dupriez B, Pardanani A, Harrison C, Hoffman R, Gisslinger H, Kroger N, Thiele J, Barbui T, Barosi G. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013 Aug 22;122(8):1395-8. doi: 10.1182/blood-2013-03-488098. Epub 2013 Jul 9. PubMed 23838352 ↗
  • Barosi G, Mesa R, Finazzi G, Harrison C, Kiladjian JJ, Lengfelder E, McMullin MF, Passamonti F, Vannucchi AM, Besses C, Gisslinger H, Samuelsson J, Verstovsek S, Hoffman R, Pardanani A, Cervantes F, Tefferi A, Barbui T. Revised response criteria for polycythemia vera and essential thrombocythemia: an ELN and IWG-MRT consensus project. Blood. 2013 Jun 6;121(23):4778-81. doi: 10.1182/blood-2013-01-478891. Epub 2013 Apr 16. PubMed 23591792 ↗
  • Tefferi A, Guglielmelli P, Larson DR, Finke C, Wassie EA, Pieri L, Gangat N, Fjerza R, Belachew AA, Lasho TL, Ketterling RP, Hanson CA, Rambaldi A, Finazzi G, Thiele J, Barbui T, Pardanani A, Vannucchi AM. Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood. 2014 Oct 16;124(16):2507-13; quiz 2615. doi: 10.1182/blood-2014-05-579136. Epub 2014 Jul 18. PubMed 25037629 ↗
  • Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner EO, Lyons RM, Raza A, Vaddi K, Sun W, Peng W, Sandor V, Kantarjian H; COMFORT-I investigators. Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I. Haematologica. 2015 Apr;100(4):479-88. doi: 10.3324/haematol.2014.115840. Epub 2015 Jan 23. PubMed 25616577 ↗
  • Newberry KJ, Patel K, Masarova L, Luthra R, Manshouri T, Jabbour E, Bose P, Daver N, Cortes J, Kantarjian H, Verstovsek S. Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation. Blood. 2017 Aug 31;130(9):1125-1131. doi: 10.1182/blood-2017-05-783225. Epub 2017 Jul 3. PubMed 28674026 ↗
  • Vannucchi AM, Guglielmelli P. Traffic lights for ruxolitinib. Blood. 2017 Aug 31;130(9):1075-1077. doi: 10.1182/blood-2017-07-795880. No abstract available. PubMed 28860323 ↗
  • Huang J, Tefferi A. Erythropoiesis stimulating agents have limited therapeutic activity in transfusion-dependent patients with primary myelofibrosis regardless of serum erythropoietin level. Eur J Haematol. 2009 Aug;83(2):154-5. doi: 10.1111/j.1600-0609.2009.01266.x. Epub 2009 Apr 10. No abstract available. PubMed 19366369 ↗
  • Akel S, Petrow-Sadowski C, Laughlin MJ, Ruscetti FW. Neutralization of autocrine transforming growth factor-beta in human cord blood CD34(+)CD38(-)Lin(-) cells promotes stem-cell-factor-mediated erythropoietin-independent early erythroid progenitor development and reduces terminal differentiation. Stem Cells. 2003;21(5):557-67. doi: 10.1634/stemcells.21-5-557. PubMed 12968110 ↗
  • Soderberg SS, Karlsson G, Karlsson S. Complex and context dependent regulation of hematopoiesis by TGF-beta superfamily signaling. Ann N Y Acad Sci. 2009 Sep;1176:55-69. doi: 10.1111/j.1749-6632.2009.04569.x. PubMed 19796233 ↗
  • Scandura JM, Boccuni P, Massague J, Nimer SD. Transforming growth factor beta-induced cell cycle arrest of human hematopoietic cells requires p57KIP2 up-regulation. Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15231-6. doi: 10.1073/pnas.0406771101. Epub 2004 Oct 11. PubMed 15477587 ↗
  • Brenet F, Kermani P, Spektor R, Rafii S, Scandura JM. TGFbeta restores hematopoietic homeostasis after myelosuppressive chemotherapy. J Exp Med. 2013 Mar 11;210(3):623-39. doi: 10.1084/jem.20121610. Epub 2013 Feb 25. PubMed 23440043 ↗
  • Chabanon A, Desterke C, Rodenburger E, Clay D, Guerton B, Boutin L, Bennaceur-Griscelli A, Pierre-Louis O, Uzan G, Abecassis L, Bourgeade MF, Lataillade JJ, Le Bousse-Kerdiles MC. A cross-talk between stromal cell-derived factor-1 and transforming growth factor-beta controls the quiescence/cycling switch of CD34(+) progenitors through FoxO3 and mammalian target of rapamycin. Stem Cells. 2008 Dec;26(12):3150-61. doi: 10.1634/stemcells.2008-0219. Epub 2008 Aug 28. PubMed 18757300 ↗
  • Zermati Y, Fichelson S, Valensi F, Freyssinier JM, Rouyer-Fessard P, Cramer E, Guichard J, Varet B, Hermine O. Transforming growth factor inhibits erythropoiesis by blocking proliferation and accelerating differentiation of erythroid progenitors. Exp Hematol. 2000 Aug;28(8):885-94. doi: 10.1016/s0301-472x(00)00488-4. PubMed 10989189 ↗
  • Zhou L, Nguyen AN, Sohal D, Ying Ma J, Pahanish P, Gundabolu K, Hayman J, Chubak A, Mo Y, Bhagat TD, Das B, Kapoun AM, Navas TA, Parmar S, Kambhampati S, Pellagatti A, Braunchweig I, Zhang Y, Wickrema A, Medicherla S, Boultwood J, Platanias LC, Higgins LS, List AF, Bitzer M, Verma A. Inhibition of the TGF-beta receptor I kinase promotes hematopoiesis in MDS. Blood. 2008 Oct 15;112(8):3434-43. doi: 10.1182/blood-2008-02-139824. Epub 2008 May 12. PubMed 18474728 ↗
  • Komrokji R, Garcia-Manero G, Ades L, Prebet T, Steensma DP, Jurcic JG, Sekeres MA, Berdeja J, Savona MR, Beyne-Rauzy O, Stamatoullas A, DeZern AE, Delaunay J, Borthakur G, Rifkin R, Boyd TE, Laadem A, Vo B, Zhang J, Puccio-Pick M, Attie KM, Fenaux P, List AF. Sotatercept with long-term extension for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial. Lancet Haematol. 2018 Feb;5(2):e63-e72. doi: 10.1016/S2352-3026(18)30002-4. Epub 2018 Jan 10. PubMed 29331635 ↗
  • Platzbecker U, Germing U, Gotze KS, Kiewe P, Mayer K, Chromik J, Radsak M, Wolff T, Zhang X, Laadem A, Sherman ML, Attie KM, Giagounidis A. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 2017 Oct;18(10):1338-1347. doi: 10.1016/S1470-2045(17)30615-0. Epub 2017 Sep 1. PubMed 28870615 ↗
  • Zhang H, Kozono DE, O'Connor KW, Vidal-Cardenas S, Rousseau A, Hamilton A, Moreau L, Gaudiano EF, Greenberger J, Bagby G, Soulier J, Grompe M, Parmar K, D'Andrea AD. TGF-beta Inhibition Rescues Hematopoietic Stem Cell Defects and Bone Marrow Failure in Fanconi Anemia. Cell Stem Cell. 2016 May 5;18(5):668-81. doi: 10.1016/j.stem.2016.03.002. Epub 2016 Mar 24. PubMed 27053300 ↗
  • Herbertz S, Sawyer JS, Stauber AJ, Gueorguieva I, Driscoll KE, Estrem ST, Cleverly AL, Desaiah D, Guba SC, Benhadji KA, Slapak CA, Lahn MM. Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway. Drug Des Devel Ther. 2015 Aug 10;9:4479-99. doi: 10.2147/DDDT.S86621. eCollection 2015. PubMed 26309397 ↗
  • Badalucco S, Di Buduo CA, Campanelli R, Pallotta I, Catarsi P, Rosti V, Kaplan DL, Barosi G, Massa M, Balduini A. Involvement of TGFbeta1 in autocrine regulation of proplatelet formation in healthy subjects and patients with primary myelofibrosis. Haematologica. 2013 Apr;98(4):514-7. doi: 10.3324/haematol.2012.076752. Epub 2013 Feb 12. PubMed 23403314 ↗
  • Ciurea SO, Merchant D, Mahmud N, Ishii T, Zhao Y, Hu W, Bruno E, Barosi G, Xu M, Hoffman R. Pivotal contributions of megakaryocytes to the biology of idiopathic myelofibrosis. Blood. 2007 Aug 1;110(3):986-93. doi: 10.1182/blood-2006-12-064626. Epub 2007 May 1. PubMed 17473062 ↗
  • Gastinne T, Vigant F, Lavenu-Bombled C, Wagner-Ballon O, Tulliez M, Chagraoui H, Villeval JL, Lacout C, Perricaudet M, Vainchenker W, Benihoud K, Giraudier S. Adenoviral-mediated TGF-beta1 inhibition in a mouse model of myelofibrosis inhibit bone marrow fibrosis development. Exp Hematol. 2007 Jan;35(1):64-74. doi: 10.1016/j.exphem.2006.08.016. PubMed 17198875 ↗
  • Martyre MC, Romquin N, Le Bousse-Kerdiles MC, Chevillard S, Benyahia B, Dupriez B, Demory JL, Bauters F. Transforming growth factor-beta and megakaryocytes in the pathogenesis of idiopathic myelofibrosis. Br J Haematol. 1994 Sep;88(1):9-16. doi: 10.1111/j.1365-2141.1994.tb04970.x. PubMed 7803262 ↗
  • Zingariello M, Martelli F, Ciaffoni F, Masiello F, Ghinassi B, D'Amore E, Massa M, Barosi G, Sancillo L, Li X, Goldberg JD, Rana RA, Migliaccio AR. Characterization of the TGF-beta1 signaling abnormalities in the Gata1low mouse model of myelofibrosis. Blood. 2013 Apr 25;121(17):3345-63. doi: 10.1182/blood-2012-06-439661. Epub 2013 Mar 5. PubMed 23462118 ↗
  • Ponce CC, de Lourdes F Chauffaille M, Ihara SS, Silva MR. The relationship of the active and latent forms of TGF-beta1 with marrow fibrosis in essential thrombocythemia and primary myelofibrosis. Med Oncol. 2012 Dec;29(4):2337-44. doi: 10.1007/s12032-011-0144-1. Epub 2011 Dec 27. PubMed 22200991 ↗
  • Bock O, Loch G, Schade U, von Wasielewski R, Schlue J, Kreipe H. Aberrant expression of transforming growth factor beta-1 (TGF beta-1) per se does not discriminate fibrotic from non-fibrotic chronic myeloproliferative disorders. J Pathol. 2005 Apr;205(5):548-57. doi: 10.1002/path.1744. PubMed 15726648 ↗
  • Shehata M, Schwarzmeier JD, Hilgarth M, Hubmann R, Duechler M, Gisslinger H. TGF-beta1 induces bone marrow reticulin fibrosis in hairy cell leukemia. J Clin Invest. 2004 Mar;113(5):676-85. doi: 10.1172/JCI19540. PubMed 14991065 ↗
  • Ceglia I, Dueck AC, Masiello F, Martelli F, He W, Federici G, Petricoin EF 3rd, Zeuner A, Iancu-Rubin C, Weinberg R, Hoffman R, Mascarenhas J, Migliaccio AR. Preclinical rationale for TGF-beta inhibition as a therapeutic target for the treatment of myelofibrosis. Exp Hematol. 2016 Dec;44(12):1138-1155.e4. doi: 10.1016/j.exphem.2016.08.007. Epub 2016 Aug 31. PubMed 27592389 ↗
  • Margolskee E, Krichevsky S, Orazi A, Silver RT. Evaluation of bone marrow morphology is essential for assessing disease status in recombinant interferon alpha-treated polycythemia vera patients. Haematologica. 2017 Mar;102(3):e97-e99. doi: 10.3324/haematol.2016.153973. Epub 2016 Nov 3. No abstract available. PubMed 27810993 ↗
  • Anand S, Stedham F, Beer P, Gudgin E, Ortmann CA, Bench A, Erber W, Green AR, Huntly BJ. Effects of the JAK2 mutation on the hematopoietic stem and progenitor compartment in human myeloproliferative neoplasms. Blood. 2011 Jul 7;118(1):177-81. doi: 10.1182/blood-2010-12-327593. Epub 2011 May 11. PubMed 21562050 ↗
  • Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405. doi: 10.1182/blood-2016-03-643544. Epub 2016 Apr 11. PubMed 27069254 ↗
  • Scherber R, Dueck AC, Johansson P, Barbui T, Barosi G, Vannucchi AM, Passamonti F, Andreasson B, Ferarri ML, Rambaldi A, Samuelsson J, Birgegard G, Tefferi A, Harrison CN, Radia D, Mesa RA. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood. 2011 Jul 14;118(2):401-8. doi: 10.1182/blood-2011-01-328955. Epub 2011 May 2. PubMed 21536863 ↗
  • Mascarenhas J, Hoffman R, Talpaz M, Gerds AT, Stein B, Gupta V, Szoke A, Drummond M, Pristupa A, Granston T, Daly R, Al-Fayoumi S, Callahan JA, Singer JW, Gotlib J, Jamieson C, Harrison C, Mesa R, Verstovsek S. Pacritinib vs Best Available Therapy, Including Ruxolitinib, in Patients With Myelofibrosis: A Randomized Clinical Trial. JAMA Oncol. 2018 May 1;4(5):652-659. doi: 10.1001/jamaoncol.2017.5818. PubMed 29522138 ↗
  • Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):787-98. doi: 10.1056/NEJMoa1110556. PubMed 22375970 ↗

Study documents

  • Protocol and statistical analysis plan · Apr 9, 2024

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

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 2, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04103645
Lead sponsor
Weill Medical College of Cornell University
Responsible party
Sponsor
First posted
Sep 25, 2019
Start date
Nov 22, 2019
Primary completion
Jul 10, 2024
Completion
Jul 10, 2024
Results posted
Jul 2, 2025
Last update
Jul 2, 2025

Study contacts

Joseph M Scandura, MD, PhD
principal investigator · Weill Medical College of Cornell University

Oversight

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

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