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

Study on Adding an Investigational Medication to Chemotherapy for High-Risk Leukemia

S
Sandeep Batra, MD

Primary Investigator

Not Recruiting
1 year - 25 years
All
Phase 3
80 participants needed
2 Locations

Brief description of study

This phase III trial studies whether inotuzumab ozogamicin added to post-induction chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves outcomes. 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. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells in a targeted way and delivers calicheamicin 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. This trial will also study the outcomes of patients with mixed phenotype acute leukemia (MPAL) and disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk ALL chemotherapy.
 
THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic. 
 
Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic Leukemia (HR B-ALL). 
 
The first part of the study includes the first two phases of therapy: Induction and Consolidation. This part will collect information on the leukemia, as well as the effects of the initial treatment, to classify patients into post-consolidation treatment groups. On the second part of this study, patients with HR B-ALL will receive the remainder of the chemotherapy cycles (interim maintenance I, delayed intensification, interim maintenance II, maintenance), with some patients randomized to receive inotuzumab. The patients that receive inotuzumab will not receive part of delayed intensification. Other aims of this study include investigating whether treating both males and females with the same duration of chemotherapy maintains outcomes for males who have previously been treated for an additional year compared to girls, as well as to evaluate the best ways to help patients adhere to oral chemotherapy regimens. 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.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Central Nervous System Leukemia, Mixed Phenotype Acute Leukemia, Testicular Leukemia, Cancer, Riley
  • Age: 1 year - 25 years
  • Gender: All

Inclusion Criteria:
  • B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibilityudies (Part A) prior to treatment and enrollment on AALL1732. Note that centralPAL diagnosis must occur within 22 business days after enrollment forPAL patients. If not performed within this time frame, patients will be taken off.
  • APEC14B1 is not a requirement for B-LLy patients but for institutional compliancevery patient should be offered participation in APEC14B1. B-LLy patients may directlyAALL1732.
  • Patients must be > 365 days and < 25 years of age
  • White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior tohe 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:
      • Testicular leukemia
      • CNS leukemia (CNS3)
      • Steroid pretreatment.

  • 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.

  • 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, thediagnosis can be established by a pathologic diagnosis of acute leukemia on a BMbiopsy;
    • OR A complete blood count (CBC) documenting the presence of at least 1,000/uLulating leukemic cells if a bone marrow aspirate or biopsy cannot bed.
  • 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 fordiagnosis should be analogous to B-ALL. For tissue processed by other means (i.e.,blocks), the methodology and criteria for immunophenotypic analysis toblish the diagnosis of B-LLy defined by the submitting institution will bed.
  • All patients and/or their parents or legal guardians must sign a written informed.
  • All institutional, Food and Drug Administration (FDA), and NCI requirements for humanudies must be met.
Exclusion Criteria:
  • Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALLgible for AALL1731, regardless of NCI risk group).
  • With the exception of steroid pretreatment or the administration of intrathecalytarabine, patients must not have received any prior cytotoxic chemotherapy for theurrent diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior toherapy on AALL1732.
  • Patients who have received > 72 hours of hydroxyurea within one week prior to start ofystemic protocol therapy.
  • Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrowubmitted for APEC14B1 testing and who do not have a peripheral blood sample submittedg > 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 steroidhe 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 asymphoblastic lymphoma.
  • Patients with known Charcot-Marie-Tooth disease.
  • Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,gardless of blast immunophenotype.
  • Patients requiring radiation at diagnosis.
  • Female patients who are pregnant, since fetal toxicities and teratogenic effects havebeen noted for several of the study drugs. A pregnancy test is required for femalehildbearing potential.
  • Lactating women who plan to breastfeed their infants while on study and for 2 monthshe last dose of inotuzumab ozogamicin.
  • Sexually active patients of reproductive potential who have not agreed to use anve contraceptive method for the duration of study participation. For thosedomized to inotuzumab ozogamicin, there is a minimum of 8 months after thedose of inotuzumab ozogamicin for females and 5 months after the last dose ofuzumab ozogamicin for males.

This study investigates the effectiveness of adding an investigational medication to post-induction chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL). It also examines outcomes for patients with mixed phenotype acute leukemia (MPAL) and B-lymphoblastic lymphoma (B-LLy) treated with standard chemotherapy. B-ALL is a type of cancer that affects the white blood cells, which are important for fighting infections.

The study involves different phases of treatment, including induction and consolidation, to gather information and classify patients for further treatment. Some patients will receive an investigational medication, which is a monoclonal antibody linked to chemotherapy, during their treatment. This approach aims to target and kill cancer cells more effectively. The study will also explore treatment durations for males and females and strategies to help patients stick to their oral chemotherapy schedules.

  • Who can participate: Participants must be between 1 and 24 years old with newly diagnosed B-ALL, MPAL, or B-LLy. Eligibility includes specific white blood cell counts and diagnosis confirmed by bone marrow tests.
  • Study details: Participants will receive chemotherapy treatment, with some receiving an investigational medication. This investigational medication is a monoclonal antibody combined with chemotherapy to target cancer cells. A placebo, an inactive substance that looks like the investigational medicine but does not contain any medicine, may be used.
Updated on 22 Dec 2025. Study ID: PHO-COG-AALL1732, 1911161203

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