NCT03959085ClinicalTrials.gov

Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy

A Phase 3 Randomized Trial of Inotuzumab Ozogamicin (IND#:133494, NSC#: 772518) for Newly Diagnosed High-Risk B-ALL; Risk-Adapted Post-Induction Therapy for High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and Disseminated B-LLy

RecruitingTaking participants now, according to the registry record.

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In brief

Phase 35,951 participants sought231 sites5 countries

Registered in 1 registry

ClinicalTrials.govNCT03959085Open this record at ClinicalTrials.govSynced 4 weeks ago

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Trial information is shown as published by the registry, in its original language.

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How this study is set up

The points below are drawn from the public registry record for this study. Each one cites the field or sentence it came from. A dash (—) means the record does not state something — not that it is missing or wrong. Many well-run studies, especially small ones, leave some of these blank.

Present: Registered before enrolment beganFirst posted 2019-05-22; recorded start 2019-10-31
Present: Has a defined primary outcomeA primary outcome measure is listed in the record
Present: The primary outcome states a time frameThe primary outcome measure records a time frame
Present: Participants are randomly assignedAllocation is recorded as randomised
Present: Has a comparison groupThe record lists a placebo or comparator arm, or more than one study arm
Not stated: Open label (no blinding)Masking is recorded as none (open label)
Not stated: An ethics committee is not stated in the registry recordThis registry's ingested record has no ethics-committee field
Not stated: Regulatory oversight (such as an IND or IDE) is not stated in the registry recordThis registry's ingested record has no regulatory-authorisation field
Not stated: A data monitoring committee is not stated in the registry recordThis registry's ingested record has no data-monitoring-committee fieldA data monitoring committee is not required for many smaller studies, and its absence here is not unusual.
Present: No cost to participants is mentioned in the recordChecked the summary, description and eligibility text; no cost-to-participant phrase found
Present: Sponsor has 183 other studies in this databaseCounted from the lead sponsor named in the record (Children's Oncology Group)
Present: Sponsor has posted results for at least one studyBased on the sponsor’s studies in this database

The record lists 5 conditions.
Lead sponsor type recorded as: research network.
Intervention regulatory context: investigational, within a phased regulatory pathway.

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What these facts mean, and what to ask · ruleset v1

Trial stature

Three independent measures of this study, described from its registry record — not a recommendation about it. A rigorous study by investigators nobody has heard of is better evidence than a weak study led by a famous one. How these are scored.

Methodological rigourSTRONG

A strong methodological design for a phase 3 study, judged from its ClinicalTrials.gov record.

How this score is built

Randomised allocation20/20
Participants are randomly allocated between arms
Blinding0/20
Open-label
Control arm15/15
Active-comparator control arm
Primary-outcome specificity10/10
Named primary outcome with a defined time frame
Endpoint type10/10
Mortality / MACE endpoint (hard clinical outcome)
Multi-centre8/8
Multi-centre: 231 sites
Data monitoring committee0/7
No data monitoring committee stated
Prospective registration5/5
Registered before the study start date
Protocol / SAP posted0/5
No protocol or SAP posted to the registry

ScaleLARGE

A large study, international in scope: 5,951 participants (target), run at 231 sites, across 5 countries.

How this score is built

Enrolment36/40
5,951 participants (target)
Site count25/25
231 sites
Country count7/15
5 countries
Planned duration10/10
Planned over about 151 months
Sponsor scale9/10
Children's Oncology Group has led 182 trials in our corpus

Investigator standingUNKNOWN

We have no verifiable track record for the investigator named on this trial. That is common for early-career investigators and for records held outside ClinicalTrials.gov — it is not a negative signal.

How this score is built

Investigator standing0/100
No investigator recorded in the registry for this trial

These describe the registry record only, and today we hold ClinicalTrials.gov data. Absent fields lower a score, and absence often reflects registration practice rather than study quality. A high-stature trial is not necessarily safer or a better choice for you — enrolling in a large definitive trial can mean a higher chance of receiving placebo, while a small early-phase study may be the only route to a new therapy.

Summary

This phase III trial studies whether inotuzumab ozogamicin added to post-induction chemotherapy and immunotherapy (chemo-immunotherapy) for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves outcomes. Inotuzumab ozogamicin is a monoclonal antibody, which is a type of protein that can bind to certain targets on the surface of cells. Inotuzumab ozogamicin is a monoclonal antibody that is linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells by binding to the CD22 protein on the surface of the cancer cell and delivering calicheamicin inside the cells to kill them. Other drugs used in the chemotherapy regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin, methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and pegaspargase or calaspargase pegol work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Blinatumomab is a specialized type of monoclonal antibody known as a bispecific T-cell engager (BiTE). It works by simultaneously binding to CD19 on cancer cells and CD3 on normal immune cells, bringing them together to destroy leukemia cells. Blinatumomab is a standard part of chemo-immunotherapy treatment for B-ALL. This trial also studies the outcomes of patients with mixed phenotype acute leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without inotuzumab ozogamicin or blinatumomab. The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard of care chemo-immunotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic Leukemia (HR B-ALL). The first part of the study includes the first phase of therapy: Induction. This part will collect information on the leukemia, as well as the effects of the initial treatment, to classify patients into post-induction treatment groups. On the second part of this study, patients with HR B-ALL will receive the remainder of the chemotherapy cycles (consolidation, blinatumomab block 1, interim maintenance 1, blinatumomab block 2, delayed intensification, interim maintenance 2, maintenance), with some patients randomized to receive inotuzumab. The patients that receive inotuzumab will not receive part of consolidation or part of delayed intensification. Other aims of this study include evaluating 1) side effects of treatment using patient-reported outcomes and health-related quality of life, 2) the best ways to help patients adhere to oral chemotherapy regimens, 3) the relationship between levels of inotuzumab ozogamicin in the blood and side effects, 4) the impact of chemo-immunotherapy on the immune system and risk of infection, and 5) the impact of social determinants of health on outcomes. Finally, this study will be the first to track the outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia (B-LLy) or Mixed Phenotype Acute Leukemia (MPAL) when treated with B-ALL chemotherapy.

PRIMARY OBJECTIVE: I. To compare in a randomized manner the post-induction 5-year event-free survival (EFS) for children and young adults with High Risk (HR) B-cell acute lymphoblastic leukemia (B-ALL) treated with a modified Berlin-Frankfurt-Münster (mBFM) chemo-immunotherapy backbone that includes blinatumomab and replaces Consolidation Part 2 and Delayed Intensification (DI) Part 2 with two blocks of inotuzumab ozogamicin, versus those treated with a full mBFM chemo-immunotherapy backbone that includes blinatumomab and retains Consolidation Part 2 and DI Part 2 without the addition of inotuzumab ozogamicin. SECONDARY OBJECTIVES: I. To describe the 5-year disease-free survival (DFS) for a favorable risk subset of National Cancer Institute (NCI) HR B-ALL (HR-Fav) when treated with mBFM chemotherapy with a single high-dose methotrexate (HD-MTX) interim maintenance (IM) phase and treatment duration of 2 years from the start of IM regardless of sex. (Pre-Amendment #7B) II. To determine the toxicity and tolerability of inotuzumab ozogamicin integrated into the mBFM chemotherapy backbone in HR B-ALL, including toxicity experienced during phases of therapy subsequent to inotuzumab ozogamicin. III. To describe the 5-year event-free survival (EFS) for patients with mixed phenotype acute leukemia (MPAL) receiving mBFM HR B-ALL therapy that includes a second IM phase with Capizzi intravenous (IV) methotrexate without leucovorin rescue plus pegaspargase or calaspargase pegol (C-MTX). IV. To describe the 5-year EFS for patients with disseminated (Murphy stage III-IV) B-cell lymphoblastic lymphoma (B-LLy) receiving mBFM HR B-ALL therapy that includes a second IM phase with C-MTX. V. To compare health-related quality of life (HRQoL) for randomized HR B-ALL patients by study arm at two defined time points: Consolidation Part 2 Day 43 (Arm D)/inotuzumab ozogamicin Block 1 Day 15 (Arm E) and day 1 of IM2 (Arms D and E). VI. To compare symptomatic adverse events (AEs) for patients with HR B-ALL by study arm using Patient Reported Outcome (PRO) Measures. EXPLORATORY OBJECTIVES: I. To describe the 5-year overall survival (OS) and cumulative incidence of relapse (CIR) for randomized patients with HR B-ALL. II. To describe the therapy administered, disease response, and survival outcomes of patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy either during Induction, at end of induction (EOI), or at end of consolidation (EOC). III. To define the prevalence and significance of minimal marrow disease (MMD) at diagnosis and bone marrow minimal residual disease (MRD) at EOI in disseminated B-LLy. IV. To determine the impact of proposed adherence-enhancing interventions on adherence to oral mercaptopurine in patients with ALL. V. To characterize the pharmacokinetics (PK) of inotuzumab ozogamicin when administered in the setting of first remission in pediatric and young adult patients with HR B-ALL. VI. To explore associations between family-reported social determinants of health and survival outcomes, toxicities, and blinatumomab patterns of delivery. VII. To describe both the short- and long-term impact of chemo-immunotherapy on measures of immune function and infectious toxicities. OUTLINE: B-ALL: All patients with B-ALL receive Induction therapy: INDUCTION: Patients receive cytarabine intrathecally (IT) on day 1. Patients also receive vincristine intravenously (IV) on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes days 1, 8, 15, and 22, pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase intramuscularly (IM) on day 4, and methotrexate IT on days 8 and 29 (and on days 15 and 22 for central nervous system \[CNS\]3 patients). Patients \< 10 years old receive dexamethasone orally (PO) twice daily (BID) or IV on days 1-14; patients \>= 10 years old receive prednisone or prednisolone PO BID or IV on days 1-28. Treatment continues for 5 weeks in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 22 years of age. After completion of Induction treatment, patients with HR Fav B-ALL discontinue study, and patients with HR B-ALL and CD22 positive at diagnosis are randomized to Arm D or Arm E. ARM D * CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO QD on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 (also days 29 and 43 for CNS3 patients), vincristine IV on days 15, 22, 43, and 50, pegaspargase IM or IV over 1-2 hours OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on days 15 and 43. Consolidation treatment continues for 57 days in the absence of disease progression or unacceptable toxicity. Patients with testicular disease at diagnosis also receive radiation therapy (RT) to the testes once daily (QD) over 12 treatment fractions. After completion of Consolidation treatment, patients with MRD ≥ 25% discontinue study treatment. * BLINATUMOMAB (BLINA) BLOCK 1: Patients receive dexamethasone PO or IV on day 1 (and day 8 for patients with MRD ≥ 5% - \<25% at end of Consolidation \[EOC\]), blinatumomab IV continuously on days 1-28, and methotrexate IT on day 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. After completion of Blina Block 1 treatment, patients with MRD ≥ 0.01% discontinue study treatment. * INTERIM MAINTENANCE 1: Patients receive vincristine IV on days 1, 15, 29, and 43, high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, mercaptopurine PO QD on days 1-14, 15-28, 29-42, and 43-56, and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. * BLINA BLOCK 2: Patients receive blinatumomab IV continuously on days 1-28 and methotrexate IT on day 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. * DELAYED INTENSIFICATION PART 1: Patients receive methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV on days 1, 8, and 15, doxorubicin IV over 3-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase IM or IV over 1-2 hours OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on day 4 in the absence of disease progression or unacceptable toxicity. Patients then proceed to Delayed Intensification Part 2. * DELAYED INTENSIFICATION PART 2: Patients receive cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO QD on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, methotrexate IT on days 29 and 36, vincristine IV on days 43 and 50, and pegaspargase IM or IV over 1-2 hours OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on day 43. Delayed Intensification Part 1 and 2 treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. * INTERIM MAINTENANCE 2: Patients receive vincristine IV on days 1, 11, 21, 31 and 41, methotrexate IV over 2-5 or 10-15 minutes on days 1, 11, 21, 31 and 41, methotrexate IT on days 1 and 31, and pegaspargase IM or IV over 1-2 hours on days 2 and 22 OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on days 2 and 23. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. * MAINTENANCE: Patients receive vincristine IV on day 1 of each cycle, prednisone or prednisolone PO BID or IV on days 1-5 of each cycle, mercaptopurine PO QD on days 1-84 of each cycle, methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of each cycle, and methotrexate IT on day 1 of each cycle. Patients with CNS3 at diagnosis also receive cranial RT over 10 treatment fractions QD, 5 days per week, during the first 4 weeks of Maintenance treatment. Cycles repeat every 84 days until 2 years from start of Blina Block 1 treatment in the absence of disease progression or unacceptable toxicity. ARM E: * CONSOLIDATION PART 1: Patients receive cyclophosphamide IV over 30-60 minutes on day 1, cytarabine IV over 1-30 minutes or SC on days 1-4 and 8-11, mercaptopurine PO QD on days 1-14, methotrexate IT on days 1, 8, 15, and 22 (NOTE: Patients with CNS3 omit days 15 and 22), vincristine IV on days 15 and 22, and pegaspargase IM or IV over 1-2 hours OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on day 15. Treatment continues for 29 days in the absence of disease progression or unacceptable toxicity. Patients with testicular disease at diagnosis also receive RT to the testes QD over 12 treatment fractions. * INOTUZUMAB OZOGAMICIN (InO) BLOCK 1: Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15 and methotrexate IT on day 1 (and day 15 for patients with CNS3). Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. After completion of InO Block 1 treatment, patients with MRD ≥ 25% discontinue study treatment. * BLINA BLOCK 1: Patients receive dexamethasone PO or IV on day 1 (and day 8 for patients with MRD ≥ 5% - \<25% at end of InO Block 1), blinatumomab IV continuously on days 1-28, and methotrexate IT on day 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. After completion of Blina Block 1 treatment, patients with MRD ≥ 0.01% discontinue study treatment. * INTERIM MAINTENANCE 1: Patients receive vincristine IV on days 1, 15, 29, and 43, high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, mercaptopurine PO QD on days 1-14, 15-28, 29-42, and 43-56, and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. * BLINA BLOCK 2: Patients receive blinatumomab IV continuously on days 1-28 and methotrexate IT on day 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. * DELAYED INTENSIFICATION PART 1: Patients receive methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV on days 1, 8, and 15, doxorubicin IV over 3-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase IM or IV over 1-2 hours OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on day 4 in the absence of disease progression or unacceptable toxicity. Patients then proceed to Delayed Intensification Part 2. * InO BLOCK 2: Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15 and methotrexate IT on day 1. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. * INTERIM MAINTENANCE 2: Patients receive vincristine IV on days 1, 11, 21, 31 and 41, methotrexate IV over 2-5 or 10-15 minutes on days 1, 11, 21, 31 and 41, methotrexate IT on days 1 and 31, and pegaspargase IM or IV over 1-2 hours on days 2 and 22 OR calaspargase pegol (\< 22 years of age only) IV over 1-2 hours on days 2 and 23. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. * MAINTENANCE: Patients receive vincristine IV on day 1 of each cycle, prednisone or prednisolone PO BID or IV on days 1-5 of each cycle, mercaptopurine PO QD on days 1-84 of each cycle, methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of each cycle, and methotrexate IT on day 1 of each cycle. Patients with CNS3 at diagnosis also receive cranial RT over 10 treatment fractions QD, 5 days per week, during the first 4 weeks of Maintenance treatment. Cycles repeat every 84 days for 2 years in the absence of disease progression or unacceptable toxicity. ARM I: MPAL * INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes days 1, 8, 15, and 22, pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4, and methotrexate IT on days 8 and 29 (and on days 15 and 22 for CNS3 patients). Patients \< 10 years old receive dexamethasone PO BID or IV on days 1-14; patients \>= 10 years old receive prednisone or prednisolone PO BID or IV on days 1-28. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 22 years of age. Patients with MRD ≥ 5% at EOI discontinue study treatment. * CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 (excluded on days 15 and 22 for CNS3 patients), vincristine IV on days 15, 22, 43, and 50, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 15 and 43. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. Patients with testicular disease at diagnosis that does not resolve by EOC and continued evidence of testicular disease at end of induction (EOI) undergo testicular RT over 12 once-daily fractions. Calaspargase pegol can only be given to patients less than 22 years of age. Patients with MRD ≥ 0.01% at EOC discontinue study treatment. ARM II: B-LLY * INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes days 1, 8, 15, and 22, pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4, and methotrexate IT on days 8 and 29 (and on days 15 and 22 for CNS3 patients). Patients \< 10 years old receive dexamethasone PO BID or IV on days 1-14; patients \>= 10 years old receive prednisone or prednisolone PO BID or IV on days 1-28. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 22 years of age. * CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 (excluded on days 15 and 22 CNS3 patients), vincristine IV on days 15, 22, 43, and 50, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on days 15 and 43. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. Patients with testicular disease at diagnosis that does not resolve by the EOI will and continued evidence of testicular disease at EOI undergo testicular RT over 12 once-daily fractions. Calaspargase pegol can only be given to patients less than 22 years of age. Patients without complete response (CR) at EOC discontinue study treatment. ARM I AND II: MPAL AND B-LLY (POST-CONSOLIDATION THERAPY) * INTERIM MAINTENANCE 1: Patients receive vincristine IV on days 1, 15, 29, and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, methotrexate IT on days 1 and 29 and mercaptopurine PO QD on days 1-14, 15-28, 29-42, and 43-56. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. * DELAYED INTENSIFICATION (PART 1): Patients receive methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV on days 1, 8, and 15, doxorubicin IV over 3-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 4. Treatment (Parts 1 and 2 of Delayed Intensification) continues for 63 days in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 22 years of age. * DELAYED INTENSIFICATION (PART 2): Patients receive cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, methotrexate IT on days 29 and 36, vincristine IV or IV push over 1 minute on days 43 and 50, and pegaspargase or calaspargase pegol IV over 1-2 hours or pegaspargase IM on day 43. Treatment (Parts 1 and 2 of Delayed Intensification) continues for 63 days in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 22 years of age. * INTERIM MAINTENANCE 2: Patients receive vincristine IV on days 1, 11, 21, 31, and 41, methotrexate IV or infusion over 2-15 minutes or 10-15 minutes on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase or calaspargase pegol IV over 1-2 hours on days 2 and 22 (pegaspargase) or (calaspargase) 23 or pegaspargase IM on days 2 and 22. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. Calaspargase pegol can only be given to patients less than 22 years of age. * MAINTENANCE: Patients receive vincristine IV on days 1, prednisone or prednisolone PO BID or IV on days 1-5, mercaptopurine PO on days 1-84, methotrexate PO on days 8, 15, 22, 29 (excluded in cycles 1 and 2), 36, 43, 50, 57, 64, 71, and 78, and methotrexate IT on days 1 (and 29 of cycles 1-2 for patients who do not receive cranial radiation). Cycles repeat every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients with CNS3 disease at diagnosis undergo cranial radiation therapy for 10 fractions over 4 weeks. Patients undergo blood sample collection and bone marrow aspiration and biopsy on study. B-LLy patients undergo computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and/or bone scan on study. After completion of study treatment, patients are followed up at 4 weeks, then every 3 months for 2 years, every 4-6 months for the third year, then every 6-12 months for years 4-5.

Conditions

B Acute Lymphoblastic Leukemia
B Lymphoblastic Lymphoma
Central Nervous System Leukemia
Mixed Phenotype Acute Leukemia
Testicular Leukemia

Eligibility

Eligibility
Sex	All
Ages	365 Days – 25 Years
Healthy volunteers	No

Eligibility as written in the registry

Inclusion Criteria: * B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility studies (Part A) prior to treatment and enrollment on AALL1732. Note that central confirmation of MPAL diagnosis must occur within 22 days of enrollment for suspected MPAL patients. If not performed within this time frame, patients will be taken off protocol. * APEC14B1 is not a requirement for B-LLy patients but for institutional compliance every patient should be offered participation in APEC14B1. B-LLy patients may directly enroll on AALL1732. * Patients must be \> 365 days and \< 25 years of age * Initial white blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to the start of protocol-directed systemic therapy): * Age 1-9.99 years: WBC \>= 50,000/uL * Age 10-24.99 years: Any WBC * Age 1-9.99 years: WBC \< 50,000/uL with one or more of the following: * Testicular leukemia * CNS leukemia (CNS3) * Steroid pretreatment. * Initial white blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to the start of protocol-directed systemic therapy): * Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found on central confirmatory testing to have B-ALL must meet the B-ALL criteria above (age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL stratum before the end of induction. * Patient has newly diagnosed B-ALL or MPAL (by World Health Organization \[WHO\] 2016 criteria) with \>= 25% blasts on a bone marrow (BM) aspirate; * OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM biopsy; * OR A complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells if a bone marrow aspirate or biopsy cannot be performed. * Patient has newly diagnosed B-LLy Murphy stages III or IV. * Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment. * Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted. * Central nervous system (CNS) status must be determined prior to enrollment based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment and cytoreduction. Note that once cerebrospinal fluid (CSF) has been collected, protocol therapy can be initiated while final determination of CNS status is pending. It is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncture. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic chemotherapy must begin within 72 hours of this intrathecal therapy. * Direct bilirubin \< 2.0 mg/dL (34 micromoles/L) * Alanine aminotransferase (ALT) ≤ 10x upper limit of normal (ULN). For the purposes of this study, the ULN for ALT is defined as 45 U/L * Exceptions to this include patients with known Gilbert's Syndrome, or those with hepatic involvement from leukemic or lymphomatous infiltration * All patients and/or their parents or legal guardians must sign a written informed consent. * All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met. Exclusion Criteria: * Patients with Down syndrome are not eligible * With the exception of steroid pretreatment and steroid cytoreduction or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1732. * Patients who have received \> 72 hours of hydroxyurea within one week prior to start of systemic protocol therapy. * Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted containing \> 1,000/uL circulating leukemia cells. * Patients with acute undifferentiated leukemia (AUL) are not eligible. * For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid pretreatment, the following additional exclusion criteria apply: * T-lymphoblastic lymphoma. * Morphologically unclassifiable lymphoma. * Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma. * Patients with known Charcot-Marie-Tooth disease. * Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype. * Patients requiring radiation at diagnosis. * Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential. * Lactating women who plan to breastfeed their infants while on study and for 2 months after the last dose of inotuzumab ozogamicin. * Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of study participation. For those patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the last dose of inotuzumab ozogamicin for females and 5 months after the last dose of inotuzumab ozogamicin for males.

Eligibility in plain statements

This record's criteria have not been broken into separate statements yet. The registry text above is complete and is the authoritative version.

Study design

Study design
Study type	Interventional
Phase	Phase 3
Allocation	Randomised
Intervention model	PARALLEL
Primary purpose	TREATMENT
Masking	NONE (0)
Enrolment	5,951 participants sought

Sponsor and collaborators

Children's Oncology Group Sponsor
National Cancer Institute (NCI) Collaborators

Arms and interventions

Arm D (CD 22 positive HR B-ALL)ACTIVE_COMPARATOR
See detailed description for Arm D.
Arm E (CD22 positive HR B-ALL)EXPERIMENTAL
See detailed description for Arm E.
Arm I (MPAL)EXPERIMENTAL
See Detailed Description for Arm I.
Arm II (B-LLy)EXPERIMENTAL
See Detailed Description for Arm II.

Interventions

Procedure Biospecimen Collection
Undergo blood sample collection
Biological Blinatumomab
Given IV
Procedure Bone Marrow Aspiration
Undergo bone marrow aspiration
Procedure Bone Marrow Biopsy
Undergo bone marrow biopsy
Procedure Bone Scan
Undergo bone scan
Drug Calaspargase Pegol
Given IV
Procedure Computed Tomography
Undergo CT
Drug Cyclophosphamide
Given IV
Drug Cytarabine
Given IV, IT, or SC
Drug Daunorubicin Hydrochloride
Given IV
Drug Dexamethasone
Given PO or IV
Drug Doxorubicin Hydrochloride
Given IV
Biological Inotuzumab Ozogamicin
Given IV
Drug Leucovorin Calcium
Given PO or IV
Procedure Magnetic Resonance Imaging
Undergo MRI
Drug Mercaptopurine
Given PO
Drug Methotrexate
Given IT or IV
Drug Pegaspargase
Given IV or IM
Procedure Positron Emission Tomography
Undergo PET
Drug Prednisolone
Given PO or IV
Drug Prednisone
Given PO or IV
Other Questionnaire Administration
Ancillary studies
Radiation Radiation Therapy
Undergo testicular radiation therapy
Radiation Radiation Therapy
Undergo cranial radiation therapy
Drug Thioguanine
Given PO
Drug Vincristine Sulfate
Given IV

Outcome measures

Primary outcome
Post-induction 5-year event-free survival (EFS)
Will compare in a randomized manner the post-induction 5-year EFS for children and young adults with High Risk (HR) B-cell acute lymphoblastic leukemia (B-ALL) treated with a modified Berlin-Frankfurt-Münster (mBFM) chemo-immunotherapy backbone that includes blinatumomab and replaces Consolidation Part 2 and Delayed Intensification (DI) Part 2 with two blocks of inotuzumab ozogamicin, versus those treated with a full mBFM chemo-immunotherapy backbone that includes blinatumomab and retains Consolidation Part 2 and DI Part 2 without the addition of inotuzumab ozogamicin.
Time frame From study entry to first event (induction failure, induction death, end of induction [EOI] minimal residual disease [MRD] ≥ 5%,EO consolidation [C] MRD ≥ 0.01%, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years
Secondary outcome
5-year DFS for favorable risk subset of NCI HR B-ALL (HR favorable) when treated with mBFM chemotherapy with a single high-dose methotrexate (HD MTX) Interim Maintenance (IM) phase and treatment duration of 2 years from the start of IM regardless of sex
Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using ITT analysis based on randomized group.
Time frame From EOC to first event (relapse, second malignant neoplasm, remission death) or date of last contact, assessed up to 5 years
Secondary outcome
Incidence of adverse events for the integration of inotuzumab ozogamicin into the mBFM chemotherapy backbone in HR B-ALL
Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will be monitored and reported.
Time frame Up to 5 years
Secondary outcome
5-year event-free survival (EFS) for patients with mixed phenotype acute leukemia (MPAL) receiving mBFM HR B-ALL therapy that includes a second IM phase with Capizzi escalating intravenous MTX without leucovorin rescue+pegaspargase or calaspargase pegol
Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using ITT analysis based on randomized group.
Time frame From study entry to first event (induction failure, Induction death, end of induction (EOI) minimal residual disease (MRD) >= 5%, EOC MRD >= 0.01%, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years
Secondary outcome
5-year EFS for patients with disseminated (Murphy stage III-IV) B-cell lymphoblastic lymphoma (B-LLy) receiving mBFM HR B-ALL therapy that includes a second IM phase with C-MTX
Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using ITT analysis based on randomized group.
Time frame From study entry to first event (progressive disease, induction death, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years
Secondary outcome
Health-related quality of life (HRQoL) for HR B-ALL
Will compare by study arm.
Time frame Consolidation Part 2 Day 43 (Arm D)/Inotuzumab ozogamicin Block 1 Day 15 (Arm E) up to Day 1 of IM2 (Arms D and E)
Secondary outcome
Incidence of symptomatic AEs for patients with HR B-ALL
Will compare by study arm using Patient Reported Outcome (PRO) Measures.
Time frame Up to 5 years
Other outcome
Overall survival (OS)
OS rates will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto.
Time frame Time from study entry to death or date of last contact for those alive at last contact, assessed up to 5 years
Other outcome
Therapy administered to patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy
Will be described.
Time frame Up to 5 years
Other outcome
Disease response in patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy
Will be described.
Time frame Up to 5 years
Other outcome
Survival outcomes of patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy
Will be described.
Time frame Up to 5 years
Other outcome
Prevalence and significance of minimal marrow disease (MMD) at diagnosis and bone marrow MRD in disseminated B-LLy
Percentages with MMD at induction and MRD positivity at end of Induction will be described.
Time frame Up to 5 years
Other outcome
Impact of four proposed interventions of varying intensities to enhance adherence to oral 6 mercaptopurine, with a randomization based upon baseline adherence measured during the first cycle of maintenance therapy
The main analyses will use mixed models including random effects to account for the multiple sites and longitudinal observations within patients. Will examine unadjusted associations of the primary outcome (MEMS-based adherence rate) with demographic, clinical and sociodemographic variables for the entire cohort (across 3 intervention arms). Those patient-level factors associated with the outcome will be included in the main model as fixed effects to improve the precision of the estimates. The basic model for adherence will include time and mean adherence during the baseline pre-intervention period and treatment group. It will also include interactions between time and both baseline adherence and intervention group to allow for intervention-specific trends and normal changes in adherence over time.
Time frame Up to 5 years
Other outcome
DFS by sex
Estimates of DFS and the corresponding 95% confidence intervals by sex.
Time frame Up to 5 years
Other outcome
DFS by race
Estimates of DFS and the corresponding 95% confidence intervals by race.
Time frame Up to 5 years
Other outcome
DFS by ethnicity
Estimates of DFS and the corresponding 95% confidence intervals by ethnicity.
Time frame Up to 5 years
Other outcome
Pharmacokinetics (PK) of inotuzumab ozogamicin when administered in the setting of first remission in pediatric and young adult patients with HR B-ALL
PK of inotuzumab ozogamicin will be described with the Area Under the Curve (AUC) (in the PK model).
Time frame Up to 5 years
Other outcome
Family-reported social determinants of health and survival outcomes, toxicities, and blinatumomab patterns of delivery
Will explore associations between family-reported social determinants of health and survival outcomes, toxicities, and blinatumomab patterns of delivery.
Time frame Up to 5 years
Other outcome
Short- and long-term impact of chemo-immunotherapy on measures of immune function and infectious toxicities
Will describe short- and long-term impact of chemo-immunotherapy on measures of immune function and infectious toxicities.
Time frame Up to 5 years

Dates

Dates
Start date	October 31, 2019 (actual)
Primary completion	March 31, 2032 (estimated)
Completion	March 31, 2032 (estimated)
First posted	May 22, 2019 (actual)
Last updated	August 25, 2026
Results posted	Not stated in the registry record
Status last verified	June 2026

Actual means the event happened. Estimated means the sponsor expects it. The two mean different things.

Locations

212 sites are recruiting

Australia

Australia
Facility	City	State or region	Status
Monash Medical Center-Clayton Campus	Clayton	Victoria	Recruiting
John Hunter Children's Hospital	Hunter Regional Mail Centre	New South Wales	Recruiting
Women's and Children's Hospital-Adelaide	North Adelaide	South Australia	Recruiting
Royal Children's Hospital	Parkville	Victoria	Recruiting
Perth Children's Hospital	Perth	Western Australia	Recruiting
Royal Hobart Hospital	Saint Hobart	Tasmania	Recruiting
Queensland Children's Hospital	South Brisbane	Queensland	Recruiting
The Children's Hospital at Westmead	Westmead	New South Wales	Suspended

Canada

Canada
Facility	City	State or region	Status
Alberta Children's Hospital	Calgary	Alberta	Recruiting
University of Alberta Hospital	Edmonton	Alberta	Recruiting
IWK Health Centre	Halifax	Nova Scotia	Recruiting
McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Recruiting
Kingston Health Sciences Centre	Kingston	Ontario	Recruiting
Children's Hospital	London	Ontario	Recruiting
The Montreal Children's Hospital of the MUHC	Montreal	Quebec	Recruiting
Children's Hospital of Eastern Ontario	Ottawa	Ontario	Recruiting
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)	Québec		Recruiting
Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Suspended
Jim Pattison Children's Hospital	Saskatoon	Saskatchewan	Recruiting
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec	Recruiting
Janeway Child Health Centre	St. John's	Newfoundland and Labrador	Recruiting
Hospital for Sick Children	Toronto	Ontario	Recruiting
British Columbia Children's Hospital	Vancouver	British Columbia	Recruiting
CancerCare Manitoba	Winnipeg	Manitoba	Recruiting

New Zealand

New Zealand
Facility	City	State or region	Status
Christchurch Hospital	Christchurch		Recruiting
Starship Children's Hospital	Grafton	Auckland	Recruiting

Puerto Rico

Puerto Rico
Facility	City	State or region	Status
HIMA San Pablo Oncologic Hospital	Caguas		Active, not recruiting
University Pediatric Hospital	San Juan		Recruiting

United States

United States
Facility	City	State or region	Status
Children's Hospital Medical Center of Akron	Akron	Ohio	Recruiting
Albany Medical Center	Albany	New York	Recruiting
University of New Mexico Cancer Center	Albuquerque	New Mexico	Recruiting
Presbyterian Hospital	Albuquerque	New Mexico	Recruiting
Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	Recruiting
Texas Tech University Health Sciences Center-Amarillo	Amarillo	Texas	Active, not recruiting
Providence Alaska Medical Center	Anchorage	Alaska	Recruiting
C S Mott Children's Hospital	Ann Arbor	Michigan	Recruiting
Mission Hospital	Asheville	North Carolina	Recruiting
Children's Healthcare of Atlanta - Arthur M Blank Hospital	Atlanta	Georgia	Recruiting
Augusta University Medical Center	Augusta	Georgia	Recruiting
Children's Hospital Colorado	Aurora	Colorado	Recruiting
Dell Children's Medical Center of Central Texas	Austin	Texas	Recruiting
Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	Recruiting
University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	Recruiting
Sinai Hospital of Baltimore	Baltimore	Maryland	Recruiting
Eastern Maine Medical Center	Bangor	Maine	Recruiting
Walter Reed National Military Medical Center	Bethesda	Maryland	Recruiting
Children's Hospital of Alabama	Birmingham	Alabama	Recruiting
Saint Luke's Cancer Institute - Boise	Boise	Idaho	Recruiting
Tufts Children's Hospital	Boston	Massachusetts	Active, not recruiting
Massachusetts General Hospital Cancer Center	Boston	Massachusetts	Recruiting

181 further sites are listed in the registry record.

Study documents

No documents are linked in this registry record.

Changes over time

No changes have been recorded since we first ingested this record.

A change is recorded each time the sponsor updates the registry record. Status, dates, enrolment and sites appear here as they move.

Registry: ClinicalTrials.gov · NCT########

https://xmedica.io/trials/ctgov/NCT03959085

Categories

Registered in 1 registry

Interested in this study?

How this study is set up

Summary

Conditions

Eligibility

Eligibility as written in the registry

Eligibility in plain statements

Study design

Sponsor and collaborators

Arms and interventions

Interventions

Outcome measures

Dates

Locations

Australia

Canada

New Zealand

Puerto Rico

United States

Study documents

Changes over time