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CompletedNCT03677596Updated Nov 22, 2023Results posted

A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients

A Phase 4 interventional study of inotuzumab ozogamicin-dose level 2 and Inotuzumab ozogamicin-dose level 1 in Leukemia, Precursor b-Cell Lymphoblastic Leukemia-Lymphoma and ACUTE LYMPHOBLASTIC LEUKEMIA, sponsored by Pfizer. Completed at 45 sites in 8 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-11-22.

Sponsored by Pfizer · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
102
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

This study will explore 2 different doses of inotuzumab ozogamicin including the dose that is approved and a lower dose. The main purpose of this study is to evaluate whether a dose of inotuzumab ozogamicin, lower than the approved dose, could be recommended for adult patient with relapsed or refractory ALL who may be at higher risk for severe liver problems after inotuzumab ozogamicin treatment and stem cell transplant (a potentially curative therapy that can replace cancer cells with healthy cells). Efficacy and safety of the 2 doses will be evaluated.

02

Conditions studied

  • Leukemia
  • Precursor b-Cell Lymphoblastic Leukemia-Lymphoma
  • ACUTE LYMPHOBLASTIC LEUKEMIA

Keywords

  • Leukemia
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • ACUTE LYMPHOBLASTIC leukemia
  • inotuzumab ozogamicin
  • Besponsa
  • transplant
03

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 102 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

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

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Relapsed or refractory precursor CD22 positive B cell ALL with M2 or M3 marrow (≥5% blasts) and who are eligible for HSCT;

  2. Have 1 or more of the following risk factors for developing VOD:

    1. Due to receive Salvage 2 or greater;
    2. Prior HSCT;
    3. Age ≥55 years.
    4. Ongoing or prior hepatic disease which may include a prior history of hepatitis or drug induced liver injury, as well as hepatic steatosis, nonalcoholic steatohepatitis, baseline elevations of bilirubin > upper limit of normal (ULN) and ≤1.5 x ULN.
  3. Ph+ ALL patients must have failed treatment with at least 1 second or third generation tyrosine kinase inhibitor and standard multi agent induction chemotherapy;
  4. Patients in Salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy;
  5. Patients with lymphoblastic lymphoma and bone marrow involvement 5% lymphoblasts by morphologic assessment;
  6. Age 18 years to 75 years;
  7. Eastern Cooperative Oncology Group (ECOG) performance status 0 2;
  8. Adequate liver function, including total serum bilirubin ≤1.5 x ULN unless the patient has documented Gilbert syndrome, and aspartate and alanine aminotransferase (AST and ALT) ≤2.5 x ULN;
  9. Serum creatinine ≤1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of >=40 mL/min;

  10. Male and female patients of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for a minimum of 8 months (females) and 5 months (males) after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the Investigator, he/she is biologically capable of having children and is sexually active. Female subjects of nonchildbearing potential must meet at least 1 of the following criteria:

    1. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state;
    2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
    3. Have medically confirmed ovarian failure. All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
  11. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study; patients with mental capacity which requires the presence of a legally authorized representative will be excluded from the study;
  12. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion criteria

Exclusion Criteria:

  1. Isolated extramedullary relapse (ie, testicular or central nervous system);
  2. Burkitt's or mixed phenotype acute leukemia based on the WHO 2008 criteria;
  3. Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (ie, cranial nerve palsies or other significant neurologic dysfunction) within 28 days. Prophylactic intrathecal medication is not a reason for exclusion;

  4. Prior chemotherapy within 2 weeks before randomization with the following exceptions:

    1. To reduce the circulating lymphoblast count or palliation: ie, steroids, hydroxyurea or vincristine;
    2. For ALL maintenance: mercaptopurine, methotrexate, vincristine, thioguanine, and/or tyrosine kinase inhibitors.

    Patients must have recovered from acute non hematologic toxicity (to Grade 1 or less) of all previous therapy prior to enrollment.

  5. Prior monoclonal antibodies within 6 weeks of randomization, with the exception of rituximab which must be discontinued at least 2 weeks prior to randomization;
  6. Prior inotuzumab ozogamicin treatment or other anti CD22 immunotherapy within 6 months before randomization;
  7. Prior allogeneic hematopoietic stem cell transplant (HSCT) within 90 days before randomization. Patients must have completed immunosuppression therapy for treatment of graft versus host disease (GvHD) prior to enrollment. At randomization, patients must not have Grade 2 or higher acute GvHD, or extensive chronic GvHD;
  8. Peripheral absolute lymphoblast count >=10,000 /L (treatment with hydroxyurea and/or steroids/vincristine is permitted within 2 weeks of randomization to reduce the white blood cell [WBC] count);
  9. Known systemic vasculitides (eg, Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus), primary or secondary immunodeficiency (such as human immunodeficiency virus [HIV] infection or severe inflammatory disease);
  10. Active hepatitis B infection as evidenced by hepatitis B surface antigen, active hepatitis C infection (must be anti-hepatitis C antibody negative or hepatitis C ribonucleic acid negative), or known seropositivity for HIV. HIV testing may need to be performed in accordance with local regulations or local practice;
  11. Major surgery within 4 weeks before randomization;
  12. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition);
  13. Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery. Patients with previous malignancies are eligible provided that they have been disease free for >=2 years;
  14. Patients with active heart disease or the presence of New York Heart Association (NYHA) stage III or IV congestive heart failure;
  15. QTcF >470 msec (based on the average of 3 consecutive electrocardiogram [ECGs]);
  16. Myocardial infarction within 6 months before randomization;
  17. History of clinically significant ventricular arrhythmia, or unexplained syncope not believed to be vasovagal in nature, or chronic bradycardic states such as sinoatrial block or higher degrees of atrioventricular (AV) block unless a permanent pacemaker has been implanted;
  18. Uncontrolled electrolyte disorders that can compound the effects of a QTc prolonging drug (eg, hypokalemia, hypocalcemia, hypomagnesemia);
  19. Prior confirmed or ongoing hepatic veno occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS), or other serious or current ongoing liver disease such as cirrhosis or nodular regenerative hyperplasia;
  20. Administration of live vaccine within 6 weeks before randomization;
  21. Evidence of uncontrolled current serious active infection (including sepsis, bacteremia, fungemia) or patients with a recent history (within 4 months) of deep tissue infections such as fascitis or osteomyelitis;
  22. Patients who have had a severe allergic reaction or anaphylactic reaction to any humanized monoclonal antibodies;
  23. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use highly effective contraception as outlined in this protocol for the duration of the study and for a minimum of 8 months (females) and 5 months (males) after the last dose of investigational product;
  24. Investigative site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study;
  25. Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation (up through the end of treatment visit);
  26. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
102 participants (actual)

Study arms

  • Experimental
    Dose Level 2

    Inotuzumab ozogamicin at starting dose 1.2 mg/m2/cycle (administered in 3 divided doses). Most patients expected to receive 2 or 3 cycles (cycle length 21 to 28 days)

    Drug: inotuzumab ozogamicin-dose level 2

  • Active comparator
    Dose Level 1

    Inotuzumab ozogamicin at starting dose 1.8 mg/m2/cycle (administered in 3 divided doses). Most patients expected to receive 2 or 3 cycles (cycle length 21 to 28 days)

    Drug: Inotuzumab ozogamicin-dose level 1

Interventions

  • Druginotuzumab ozogamicin-dose level 2

    Inotuzumab ozogamicin (BESPONSA™) is a CD22 targeted antibody drug conjugate (ADC) approved by US FDA for treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). The approved starting dose is 1.8mg/m2/cycle. This treatment arm evaluates a lower starting dose of 1.2mg/m2/cycle.

    Also known as: Besponsa

  • DrugInotuzumab ozogamicin-dose level 1

    Inotuzumab ozogamicin (BESPONSA™) is a CD22 targeted antibody drug conjugate (ADC) approved by US FDA for treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). The approved starting dose of 1.8mg/m2/cycle is administered in this treatment arm.

    Also known as: Besponsa

06

What researchers measure

Primary outcomes

  1. Percentage of Participants With Veno-occlusive Disease (VOD)

    VOD happened when the small blood vessels that lead into the liver and were inside the liver become blocked. VOD is defined as: a. Classical VOD (first 21 days after HSCT): Bilirubin\>=2 mg/dL and 2 (or more) of the following criteria must also be present: 1. Painful hepatomegaly; 2. Weight gain \>5%; 3. Ascites. b. Late onset VOD (\>21 days after HSCT): Classical VOD beyond Day 21; or Histologically proven VOD; or Two or more of the following criteria must be present: 1. Bilirubin \>2 mg/dL; 2. Painful hepatomegaly; 3. Weight gain \>5%; 4. Ascites. and hemodynamical and/or ultrasound evidence of VOD.

    Time frame: 2 years from randomization

  2. Rate of Hematologic Remission (Complete Response [CR] / Complete Response With Incomplete Hematologic Recovery[CRi])

    CR is defined as a disappearance of leukemia as indicated by\<5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC)\>=1000/µL and platelets\>=100000/µL. C1 extramedullary disease status is required. CRi is defined as CR except with ANC \<1000/µL and/or platelets \<100000/µL. C1 defined as complete disappearance of all measurable and non-measurable extramedullary disease with the exception of lesions with following must be true: For participants with\>= 1 measurable lesion, all nodal masses\>1.5cm in greatest transverse diameter (GTD) at baseline (last assessment before 1st dose of study treatment) must must have regressed to\>=1.5cm in GTD and all nodal masses\>=1cm \& \<=1.5cm in GTD at baseline have regressed to \<1cm GTD or must have reduced by 75% in sum of products of greatest diameters. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable.

    Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

Secondary outcomes

  1. Number of Participants With Treatment-Emergent Adverse Events (All Causalities)

    Adverse event (AE) = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. On-treatment period was defined as the period starting with the 1st dose of study treatment through 63 days after last dose or 1 day before start day of new anticancer therapy, whichever occurred first. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All VOD cases were reported as SAE. Grades of severity were defined by Common terminology criteria for adverse events (CTCAE) v3.0. Grade 3=severe adverse event; Grade 4=life-threatening consequences; urgent intervention indicated. Grade 5=death related to AE. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)

  2. Number of Participants With Treatment-Emergent Adverse Events (Treatment-related)

    Adverse event (AE) = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. Treatment emergent AEs (TEAEs) were defined as AEs that reported the period starting with the first dose of study treatment drug through 63 days after last dose or 1 day before start day of new anticancer therapy, whichever occurred first. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grades of severity were defined by CTCAE v3.0. Grade 3 = severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE. Causality of TEAEs were assessed by the Investigator. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)

  3. Number of Participants With Treatment-Emergent Serious Adverse Events (Post-HSCT)

    A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All SAEs occurred after HSCT were reported in this OM. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: Starting from the first transplant after inotuzumab ozogamicin treatment and including the entire duration of subsequent follow up (approximately 52 weeks))

  4. Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

    Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Following Parameters were analyzed for laboratory assessment: Hematology (Activated partial thromboplastin time prolonged, Anemia, Hemoglobin increased, International normalization rate (INR) increased, Leukocytosis, Lymphocyte count decreased, Lymphocyte count increased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased). Grades of severity were defined by CTCAE v3.0. Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)

  5. Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

    Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Following Parameters were analyzed for laboratory assessment: Chemistry (Alanine aminotransferase increased, Alkaline phosphatase increased, Aspartate aminotransferase increased, Blood bilirubin increased, Chronic kidney disease, Creatinine increased, Gamma glutamyl transpeptidase (GGT) increased, Hypercalcemia, Hyperglycemia, Hyperkalemia, Hypermagnesemia, Hypernatremia, Hypoalbuminemia, Hypocalcemia, Hypoglycemia, Hypokalemia, Hypomagnesemia, Hyponatremia, Hypophosphatemia, Lipase increased and Serum amylase increased). Grades of severity were defined by CTCAE v3.0. Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)

  6. Number of Participants Achieving a CR/CRi With Minimal Residual Disease (MRD) Negativity

    MRD was assessed by flow cytometry for CD22 and other cell surface markers associated with B-cell ALL. In participants who achieved CR/CRi, MRD negativity was defined as defined as \<1 abnormal cell/10\^4 nucleated cells by flow cytometry per central laboratory analysis.

    Time frame: At screening, once at Day 16-28 of Cycles 1 and 2, or until CR/CRi and MRD negativity were achieved, then after every 1-2 cycles as clinically indicated, and at EOT visit (maximum of 2.5 years)

  7. Duration of Remission (DoR) in Participants Achieving CR/CRi

    DoR was defined as time from date of first response in responders (CR/CRi) to the date of disease progression (i.e., objective progression, relapse from CR/CRi, including post-study treatment follow-up disease assessments) or death due to any cause, whichever occurs first. DoR was estimated using Kaplan-Meier methods. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

  8. Progression-Free Survival

    PFS was defined as time from date of randomization to the date of disease progression (i.e., objective progression, relapse from CR/CRi, including post-study treatment follow-up disease assessments), death due to any cause, or starting new induction therapy/post-therapy HSCT without achieving CR/CRi, whichever occured first. PFS was estimated using Kaplan-Meier methods. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

  9. Overall Survival

    Overall survival was defined as the time from date of first dose of study treatment to death due to any cause. Participants without confirmation of death were censored at the date that the participant was last known to be alive. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

  10. Number of Participant Received HSCT Post Inotuzumab Ozogamicin Treatment

    Participants who underwent HSCT after inotuzumab ozogamicin treatment. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

  11. The Cumulative Incidence Rate of Post-HSCT Relapse at Month 12

    Post-HSCT relapse is defined as the time from date of first HSCT after inotuzumab ozogamicin treatment to the date of first relapse post-HSCT. Cumulative incidence rates of an event at a particular timepoint were estimated with the CI calculated based on the cumulative incidence function using the method described by Kalbfleisch RL and Prentice JD. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: From first dose of study treatment to Month 12

  12. Number of Participants With Post-HSCT Mortality

    Post-HSCT Mortality was defined as the time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

  13. Number of Participants With Post HSCT Non-Relapse Mortality

    Post HSCT non-relapse mortality was defined as time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause without prior relapse. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

  14. Number of Participants With Post HSCT Relapse-Related Mortality

    Post HSCT Relapse-Related Mortality was defined as time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause with prior relapse. Results were reported as of the data cutoff date on 21 Sep 2022.

    Time frame: From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years

  15. Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin

    Ctrough was defined as the mean Predose concentration of study treatment.

    Time frame: Pre-dose on Cycle 1 Day 1, 8 and 15, and on Day1 and 8 of Cycle 2, 3 and 4.

  16. Number of Participants With Positive Anti-Drug Antibody (ADA)

    ADA incidence is defined as combined results of treatment-boosted and treatment-induced ADA-positive participants. The immunogenicity of inotuzumab ozogamicin was evaluated using a validated electrochemiluminescence (ECL)-based immunoassay.

    Time frame: At Day 1 of every cycle prior to the beginning of inotuzumab ozogamicin infusion and at the EOT visit, up to approximately 52 weeks.

  17. Number of Participants With Positive Neutralizing Antibody (NAb)

    NAb incidence is defined as combined results of treatment-boosted and treatment-induced NAb-positive participants. The immunogenicity of inotuzumab ozogamicin was evaluated using a validated electrochemiluminescence (ECL)-based immunoassay.

    Time frame: At Day 1 of every cycle prior to the beginning of inotuzumab ozogamicin infusion and at the EOT visit, up to approximately 52 weeks.

07

Results

Posted Nov 22, 2023

Participant flow

Participant flow — Overall Study
Milestone1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase)
Started6438
Completed4119
Not completed2319
Withdrew: Adverse event01
Withdrew: Death106
Withdrew: Lost to follow-up01
Withdrew: Progressive disease88
Withdrew: Withdrawal by subject30
Withdrew: Disease relapse22
Withdrew: Other01

Outcome measures

PrimaryPercentage of Participants With Veno-occlusive Disease (VOD)

VOD happened when the small blood vessels that lead into the liver and were inside the liver become blocked. VOD is defined as: a. Classical VOD (first 21 days after HSCT): Bilirubin\>=2 mg/dL and 2 (or more) of the following criteria must also be present: 1. Painful hepatomegaly; 2. Weight gain \>5%; 3. Ascites. b. Late onset VOD (\>21 days after HSCT): Classical VOD beyond Day 21; or Histologically proven VOD; or Two or more of the following criteria must be present: 1. Bilirubin \>2 mg/dL; 2. Painful hepatomegaly; 3. Weight gain \>5%; 4. Ascites. and hemodynamical and/or ultrasound evidence of VOD.

Time frame:
2 years from randomization
Reported as:
Number · Percentage of Participants
Percentage of Participants With Veno-occlusive Disease (VOD)
Percentage of Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Percentage of Participants With Veno-occlusive Disease (VOD)9.114.312.55.3
PrimaryRate of Hematologic Remission (Complete Response [CR] / Complete Response With Incomplete Hematologic Recovery[CRi])

CR is defined as a disappearance of leukemia as indicated by\<5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC)\>=1000/µL and platelets\>=100000/µL. C1 extramedullary disease status is required. CRi is defined as CR except with ANC \<1000/µL and/or platelets \<100000/µL. C1 defined as complete disappearance of all measurable and non-measurable extramedullary disease with the exception of lesions with following must be true: For participants with\>= 1 measurable lesion, all nodal masses\>1.5cm in greatest transverse diameter (GTD) at baseline (last assessment before 1st dose of study treatment) must must have regressed to\>=1.5cm in GTD and all nodal masses\>=1cm \& \<=1.5cm in GTD at baseline have regressed to \<1cm GTD or must have reduced by 75% in sum of products of greatest diameters. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable.

Time frame:
From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Reported as:
Number · Percentage of Participants
Rate of Hematologic Remission (Complete Response [CR] / Complete Response With Incomplete Hematologic Recovery[CRi])
Percentage of Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Rate of Hematologic Remission (Complete Response [CR] / Complete Response With Incomplete Hematologic Recovery[CRi])50.083.371.968.4
SecondaryNumber of Participants With Treatment-Emergent Adverse Events (All Causalities)

Adverse event (AE) = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. On-treatment period was defined as the period starting with the 1st dose of study treatment through 63 days after last dose or 1 day before start day of new anticancer therapy, whichever occurred first. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All VOD cases were reported as SAE. Grades of severity were defined by Common terminology criteria for adverse events (CTCAE) v3.0. Grade 3=severe adverse event; Grade 4=life-threatening consequences; urgent intervention indicated. Grade 5=death related to AE. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events (All Causalities)
Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Participants with adverse events22426438
Participants with SAEs15284321
Participants with Maximum Grade 3 or 4 adverse events9223118
Participants with Maximum Grade 5 adverse events7111810
SecondaryNumber of Participants With Treatment-Emergent Adverse Events (Treatment-related)

Adverse event (AE) = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. Treatment emergent AEs (TEAEs) were defined as AEs that reported the period starting with the first dose of study treatment drug through 63 days after last dose or 1 day before start day of new anticancer therapy, whichever occurred first. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grades of severity were defined by CTCAE v3.0. Grade 3 = severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE. Causality of TEAEs were assessed by the Investigator. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events (Treatment-related)
Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Participants with AEs13183122
Participants with SAEs781510
Participants with Maximum Grade 3 or 4 AEs9112011
Participants with Maximum Grade 5 AEs1124
SecondaryNumber of Participants With Treatment-Emergent Serious Adverse Events (Post-HSCT)

A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All SAEs occurred after HSCT were reported in this OM. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
Starting from the first transplant after inotuzumab ozogamicin treatment and including the entire duration of subsequent follow up (approximately 52 weeks))
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Serious Adverse Events (Post-HSCT)
Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Number of Participants With Treatment-Emergent Serious Adverse Events (Post-HSCT)68142
SecondaryShift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Following Parameters were analyzed for laboratory assessment: Hematology (Activated partial thromboplastin time prolonged, Anemia, Hemoglobin increased, International normalization rate (INR) increased, Leukocytosis, Lymphocyte count decreased, Lymphocyte count increased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased). Grades of severity were defined by CTCAE v3.0. Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)
Reported as:
Count of participants · Participants
Shift Summary of Hematology Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline
Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Activated partial thromboplastin time prolonged - Grade 30000
Activated partial thromboplastin time prolonged - Grade 4NANANANA
Anemia - Grade 38132111
Anemia - Grade 4NANANANA
Hemoglobin increased - Grade 30000
Hemoglobin increased - Grade 4NANANANA
INR increased - Grade 30000
INR increased - Grade 4NANANANA
Leukocytosis - Grade 31010
Leukocytosis - Grade 4NANANANA
Lymphocyte count decreased - Grade 3115167
Lymphocyte count decreased - Grade 44264
Lymphocyte count increased - Grade 32133
Lymphocyte count increased - Grade 4NANANANA
Neutrophil count decreased - Grade 32687
Neutrophil count decreased - Grade 41110219
Platelet count decreased - Grade 31675
Platelet count decreased - Grade 44377
White blood cell decreased - Grade 3513189
White blood cell decreased - Grade 47101711
SecondaryShift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline

Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Following Parameters were analyzed for laboratory assessment: Chemistry (Alanine aminotransferase increased, Alkaline phosphatase increased, Aspartate aminotransferase increased, Blood bilirubin increased, Chronic kidney disease, Creatinine increased, Gamma glutamyl transpeptidase (GGT) increased, Hypercalcemia, Hyperglycemia, Hyperkalemia, Hypermagnesemia, Hypernatremia, Hypoalbuminemia, Hypocalcemia, Hypoglycemia, Hypokalemia, Hypomagnesemia, Hyponatremia, Hypophosphatemia, Lipase increased and Serum amylase increased). Grades of severity were defined by CTCAE v3.0. Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
From first dose of study treatment drug through 63 days after last dose (approximately 52 weeks)
Reported as:
Count of participants · Participants
Shift Summary of Chemistry Laboratory Test Results From Grade <=2 at Baseline to Grade 3 or 4 Post-Baseline
Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Alanine aminotransferase increased - Grade 31010
Alanine aminotransferase increased - Grade 40000
Alkaline phosphatase increased - Grade 31011
Alkaline phosphatase increased - Grade 40000
Aspartate aminotransferase increased - Grade 31340
Aspartate aminotransferase increased - Grade 40000
Blood bilirubin increased - Grade 31120
Blood bilirubin increased - Grade 40000
Chronic kidney disease - Grade 30000
Chronic kidney disease - Grade 40000
Creatinine increased - Grade 30000
Creatinine increased - Grade 40000
GGT increased - Grade 31233
GGT increased - Grade 40000
Hypercalcemia - Grade 30000
Hypercalcemia - Grade 40000
Hyperglycemia - Grade 32242
Hyperglycemia - Grade 40000
Hyperkalemia - Grade 30000
Hyperkalemia - Grade 41010
Hypermagnesemia - Grade 31011
Hypermagnesemia - Grade 40000
Hypernatremia - Grade 30000
Hypernatremia - Grade 40110
Hypoalbuminemia - Grade 31343
Hypoalbuminemia - Grade 4NANANANA
Hypocalcemia - Grade 31010
Hypocalcemia - Grade 40000
Hypoglycemia - Grade 30000
Hypoglycemia - Grade 40000
Hypokalemia - Grade 31231
Hypokalemia - Grade 41010
Hypomagnesemia - Grade 31011
Hypomagnesemia - Grade 40001
Hyponatremia - Grade 31010
Hyponatremia - Grade 40000
Hypophosphatemia- Grade 32021
Hypophosphatemia - Grade 40001
Lipase increased - Grade 33362
Lipase increased - Grade 40220
Serum amylase increased - Grade 31120
Serum amylase increased - Grade 40000
SecondaryNumber of Participants Achieving a CR/CRi With Minimal Residual Disease (MRD) Negativity

MRD was assessed by flow cytometry for CD22 and other cell surface markers associated with B-cell ALL. In participants who achieved CR/CRi, MRD negativity was defined as defined as \<1 abnormal cell/10\^4 nucleated cells by flow cytometry per central laboratory analysis.

Time frame:
At screening, once at Day 16-28 of Cycles 1 and 2, or until CR/CRi and MRD negativity were achieved, then after every 1-2 cycles as clinically indicated, and at EOT visit (maximum of 2.5 years)
Reported as:
Count of participants · Participants
Number of Participants Achieving a CR/CRi With Minimal Residual Disease (MRD) Negativity
Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Number of Participants Achieving a CR/CRi With Minimal Residual Disease (MRD) Negativity8253318
SecondaryDuration of Remission (DoR) in Participants Achieving CR/CRi

DoR was defined as time from date of first response in responders (CR/CRi) to the date of disease progression (i.e., objective progression, relapse from CR/CRi, including post-study treatment follow-up disease assessments) or death due to any cause, whichever occurs first. DoR was estimated using Kaplan-Meier methods. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Reported as:
Median · Months
Duration of Remission (DoR) in Participants Achieving CR/CRi
Months1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Duration of Remission (DoR) in Participants Achieving CR/CRi5.2 (1.9 to NA)6.5 (4.6 to 20.9)5.5 (4.6 to 20.9)6.8 (4.7 to 8.7)
SecondaryProgression-Free Survival

PFS was defined as time from date of randomization to the date of disease progression (i.e., objective progression, relapse from CR/CRi, including post-study treatment follow-up disease assessments), death due to any cause, or starting new induction therapy/post-therapy HSCT without achieving CR/CRi, whichever occured first. PFS was estimated using Kaplan-Meier methods. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Reported as:
Median · Months
Progression-Free Survival
Months1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Progression-Free Survival2.9 (1.7 to 5.8)6.3 (4.8 to 10.0)5.3 (3.4 to 7.2)6.3 (2.8 to 8.0)
SecondaryOverall Survival

Overall survival was defined as the time from date of first dose of study treatment to death due to any cause. Participants without confirmation of death were censored at the date that the participant was last known to be alive. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Reported as:
Median · Months
Overall Survival
Months1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Overall Survival4.5 (3.2 to 8.6)9.6 (6.4 to NA)7.6 (5.8 to 10.0)8.1 (5.4 to 10.4)
SecondaryNumber of Participant Received HSCT Post Inotuzumab Ozogamicin Treatment

Participants who underwent HSCT after inotuzumab ozogamicin treatment. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Reported as:
Count of participants · Participants
Number of Participant Received HSCT Post Inotuzumab Ozogamicin Treatment
Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Number of Participant Received HSCT Post Inotuzumab Ozogamicin Treatment10213112
SecondaryThe Cumulative Incidence Rate of Post-HSCT Relapse at Month 12

Post-HSCT relapse is defined as the time from date of first HSCT after inotuzumab ozogamicin treatment to the date of first relapse post-HSCT. Cumulative incidence rates of an event at a particular timepoint were estimated with the CI calculated based on the cumulative incidence function using the method described by Kalbfleisch RL and Prentice JD. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
From first dose of study treatment to Month 12
Reported as:
Number · Percentages of participants
The Cumulative Incidence Rate of Post-HSCT Relapse at Month 12
Percentages of participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
The Cumulative Incidence Rate of Post-HSCT Relapse at Month 1211.11 (0.40 to 41.66)22.53 (6.39 to 44.59)18.65 (6.46 to 35.72)16.67 (2.26 to 42.89)
SecondaryNumber of Participants With Post-HSCT Mortality

Post-HSCT Mortality was defined as the time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Reported as:
Count of participants · Participants
Number of Participants With Post-HSCT Mortality
Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Number of Participants With Post-HSCT Mortality68145
SecondaryNumber of Participants With Post HSCT Non-Relapse Mortality

Post HSCT non-relapse mortality was defined as time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause without prior relapse. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Reported as:
Count of participants · Participants
Number of Participants With Post HSCT Non-Relapse Mortality
Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Number of Participants With Post HSCT Non-Relapse Mortality55104
SecondaryNumber of Participants With Post HSCT Relapse-Related Mortality

Post HSCT Relapse-Related Mortality was defined as time from date of first HSCT after inotuzumab ozogamicin treatment to death due to any cause with prior relapse. Results were reported as of the data cutoff date on 21 Sep 2022.

Time frame:
From first dose of study treatment of 6 cycles till follow-up up to 2 years, in total approximately 2.5 years
Reported as:
Count of participants · Participants
Number of Participants With Post HSCT Relapse-Related Mortality
Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Number of Participants With Post HSCT Relapse-Related Mortality1341
SecondaryMean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin

Ctrough was defined as the mean Predose concentration of study treatment.

Time frame:
Pre-dose on Cycle 1 Day 1, 8 and 15, and on Day1 and 8 of Cycle 2, 3 and 4.
Reported as:
Mean · ng/mL
Mean Predose Concentrations (Ctrough) of Inotuzumab Ozogamicin
ng/mL1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Cycle 1 Day 1 (C1D1)1.9 ± 9.100.5 ± 1.971.3 ± 6.770.0 ± 0.00
C1D87.7 ± 20.535.0 ± 5.836.4 ± 15.615.4 ± 7.71
C1D158.9 ± 11.1427.3 ± 52.3217.4 ± 37.0925.3 ± 19.47
C2D116.4 ± 21.4318.8 ± 37.8017.6 ± 30.0239.7 ± 73.86
C2D842.6 ± 56.5746.6 ± 50.8944.6 ± 53.1352.0 ± 27.94
C3D121.4 ± 18.4613.2 ± 7.9317.3 ± 14.0927.5 ± 14.64
C3D831.9 ± 25.4332.9 ± 12.9632.5 ± 18.5260.7 ± 44.89
C4D150.0 ± 14.6425.5 ± 2.3337.7 ± 16.53—
C4D848.7 ± 7.9952.3 ± 9.5650.8 ± 8.1090.4 ± NA
SecondaryNumber of Participants With Positive Anti-Drug Antibody (ADA)

ADA incidence is defined as combined results of treatment-boosted and treatment-induced ADA-positive participants. The immunogenicity of inotuzumab ozogamicin was evaluated using a validated electrochemiluminescence (ECL)-based immunoassay.

Time frame:
At Day 1 of every cycle prior to the beginning of inotuzumab ozogamicin infusion and at the EOT visit, up to approximately 52 weeks.
Reported as:
Count of participants · Participants
Number of Participants With Positive Anti-Drug Antibody (ADA)
Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Positive Predose ADA1342
Treatment-induced ADA1011
Treatment-boosted ADA0000
SecondaryNumber of Participants With Positive Neutralizing Antibody (NAb)

NAb incidence is defined as combined results of treatment-boosted and treatment-induced NAb-positive participants. The immunogenicity of inotuzumab ozogamicin was evaluated using a validated electrochemiluminescence (ECL)-based immunoassay.

Time frame:
At Day 1 of every cycle prior to the beginning of inotuzumab ozogamicin infusion and at the EOT visit, up to approximately 52 weeks.
Reported as:
Count of participants · Participants
Number of Participants With Positive Neutralizing Antibody (NAb)
Participants1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized)
Positive Predose NAb0000
Treatment-induced NAb0000
Treatment-boosted NAb0000

Adverse events

Collected over From the first dose of study treatment drug through 63 days after last dose or 1 day before start day of new anti-cancer therapy, whichever occurs first (approximately 52 weeks).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
1.2 mg/m²/Cycle (Dose Level 2 Run-in)16/22 (72.7%)15/22 (68.2%)18/22 (81.8%)
1.2 mg/m²/Cycle (Dose Level 2 Randomized Phase)23/42 (54.8%)28/42 (66.7%)32/42 (76.2%)
1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)39/64 (60.9%)43/64 (67.2%)50/64 (78.1%)
1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase)25/38 (65.8%)21/38 (55.3%)29/38 (76.3%)
Most frequent serious events
Showing 10 of 53
Most frequent serious events
Event1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized Phase)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase)
Venoocclusive liver diseaseHepatobiliary disorders2/226/428/642/38
Febrile neutropeniaBlood and lymphatic system disorders3/224/427/644/38
Disease progressionGeneral disorders3/221/424/642/38
SepsisInfections and infestations2/224/426/641/38
Fungal infectionInfections and infestations2/220/422/640/38
PyrexiaGeneral disorders1/222/423/643/38
Tumour lysis syndromeMetabolism and nutrition disorders1/220/421/643/38
COVID-19 pneumoniaInfections and infestations0/223/423/640/38
Septic shockInfections and infestations1/223/424/640/38
Neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/220/420/642/38
Most frequent other events
Showing 10 of 35
Most frequent other events
Event1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized Phase)1.2 mg/m²/Cycle (Dose Level 2 Run-in + Randomized)1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase)
NeutropeniaBlood and lymphatic system disorders4/2216/4220/6410/38
ThrombocytopeniaBlood and lymphatic system disorders5/2214/4219/6413/38
PyrexiaGeneral disorders5/225/4210/641/38
Alanine aminotransferase increasedInvestigations5/225/4210/643/38
AnaemiaBlood and lymphatic system disorders2/229/4211/646/38
Aspartate aminotransferase increasedInvestigations4/223/427/648/38
Neutrophil count decreasedInvestigations4/221/425/644/38
LeukopeniaBlood and lymphatic system disorders2/226/428/646/38
Gamma-glutamyltransferase increasedInvestigations1/224/425/646/38
PneumoniaInfections and infestations3/221/424/640/38

Baseline characteristics

The full analysis set included all participants who were randomized into the study.

Age, Categorical
Age, Categorical(Participants)1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized Phase)1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase)Total
<=18 years0000
Between 18 and 65 years21383695
>=65 years1427
Sex: Female, Male
Sex: Female, Male(Participants)1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized Phase)1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase)Total
Female10181846
Male12242056
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized Phase)1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase)Total
Hispanic or Latino25310
Not Hispanic or Latino20363591
Unknown or Not Reported0101
Race (NIH/OMB)
Race (NIH/OMB)(Participants)1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized Phase)1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase)Total
American Indian or Alaska Native0000
Asian561122
Native Hawaiian or Other Pacific Islander0000
Black or African American0000
White17342576
More than one race0000
Unknown or Not Reported0224
ECOG Performance Status
ECOG Performance Status(Participants)1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized Phase)1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase)Total
ECOG = 09192048
ECOG = 113201346
ECOG = 20358
Body Mass Index (BMI)
Body Mass Index (BMI)(kg/m^2)1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized Phase)1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase)Total
Median24.98 (16 to 36)25.31 (17 to 39)24.78 (16 to 41)25.26 (16 to 41)
Body Surface Area (BSA)
Body Surface Area (BSA)(m^2)1.2 mg/m²/Cycle (Dose Level 2 Run-in)1.2 mg/m²/Cycle (Dose Level 2 Randomized Phase)1.8 mg/m²/Cycle (Dose Level 1 Randomized Phase)Total
Median1.86 (1 to 2)1.82 (1 to 3)1.79 (1 to 3)1.80 (1 to 3)
08

Study locations

45 sites
  • Keck Hospital of USC
    Los Angeles, California 90033, United States
  • LAC+USC Medical Center
    Los Angeles, California 90033, United States
  • USC/Norris Comprehensive Cancer Center
    Los Angeles, California 90033, United States
  • Rush University Medical Center
    Chicago, Illinois 60612, United States
  • University of Maryland- Greenebaum Comprehensive Cancer Center
    Baltimore, Maryland 21201, United States
  • Seattle Cancer Care Alliance
    Seattle, Washington 98109-1028, United States
  • University of Washington Medical Center
    Seattle, Washington 98195, United States
  • Debreceni Egyetem Klinikai Központ, Orvosi Kepalkotó Klinika, Radiológia
    Debrecen, 4032, Hungary
  • Debreceni Egyetem Klinikai Központ, Pathológiai lntézet
    Debrecen, 4032, Hungary
  • Szabolcs-Szatmar Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Korhaz, Hematologia
    Nyiregyhaza, 4400, Hungary
  • Artemis hospital
    Gurugram, Haryana 122001, India
  • Sahyadri Clinical Research and Development Centre
    Pune, Maharashtra 411004, India
  • Sahyadri Super Speciality Hospital
    Pune, Maharashtra 411004, India
  • Sahyadri Super Speciality Hospital Nagar Road
    Pune, Maharashtra 411006, India
  • Sahyadri Super Speciality Hospital
    Pune, Maharashtra 411006, India
  • Christian Medical College
    Vellore, Tamil NADU 632004, India
  • Christian Medical College Vellore- Ranipet Campus
    Ranipet - 632517, Tamil Nadu, India, 632517, India
  • Klinika Hematologii i Transplantologii, Uniwersyteckie Centrum Kliniczne
    Gdansk, 80-214, Poland
  • Instytut Hematologii i Transfuzjologii
    Warsaw, 02-776, Poland
  • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza - Radeckiego we Wroclawiu
    Wroclaw, 50-367, Poland
  • Apteka Centralna
    Wroclaw, 50-556, Poland
  • National University Hospital
    Singapore, 119074, Singapore
  • Raffles Hospital
    Singapore, 188770, Singapore
  • Raffles Radiology
    Singapore, 188770, Singapore
  • Hospital Universitario Central de Asturias
    Oviedo, Asturias 33011, Spain
  • Hospital Universitari Vall d'Hebron
    Barcelona, 08035, Spain
  • Hospital General Universitario Gregorio Maranon
    Madrid, 28007, Spain
  • Hospital Universitario Ramon y Cajal
    Madrid, 28034, Spain
  • Hospital General - Semisótano
    Sevilla, 41013, Spain
  • Hospital Universitario Virgen del Rocio
    Sevilla, 41013, Spain
  • Hospital Clinico Universitario de Valencia
    Valencia, 46010, Spain
  • Hospital Universitari i Politecnic La Fe
    Valencia, 46026, Spain
  • Changhua Christian Hospital
    Changhua, 500, Taiwan
  • National Taiwan University Hospital
    Taipei, 10002, Taiwan
  • Anadolu Health Center Hospital
    Gebze, Istanbul 41400, Turkey
  • Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Clinical Research Center
    Ankara, 06200, Turkey
  • Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital Hematology Department
    Ankara, 06200, Turkey
  • Ankara University Faculty of Medicine Cebeci Hospital Hematology Department
    Ankara, 06590, Turkey
  • Private Medstar Antalya Hosp. Hematology and Stem Cell Transplantation Center
    Antalya, 07050, Turkey
  • Marmara University Pendik Training and Research Hospital Hematology Unit
    Istanbul, 34899, Turkey
  • Ege University Medical Faculty
    Izmir, 35100, Turkey
  • Dokuz Eylul University Medical Faculty
    Izmir, 35340, Turkey
  • Medicalpark Izmir Hospital
    Izmir, 35575, Turkey
  • Erciyes Universitesi Tip Fakultesi Hastaneleri
    Kayseri, 38039, Turkey
  • Ondokuz Mayis University Faculty Of Medicine Hospital
    Samsun, 55200, Turkey
09

References and documents

Publications

  • Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704. PubMed 35622074 ↗

Study documents

  • Study protocol · May 23, 2018
  • Statistical analysis plan · Apr 29, 2022

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

Individual participant data

Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 22, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03677596
Lead sponsor
Pfizer
Responsible party
Sponsor
First posted
Sep 19, 2018
Start date
Jul 1, 2019
Primary completion
Sep 21, 2022
Completion
May 26, 2023
Results posted
Nov 22, 2023
Last update
Nov 22, 2023

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

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

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