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

Phase 3

Recruiting

• Conditions: B Acute Lymphoblastic Leukemia; B Lymphoblastic Lymphoma; Central Nervous System Leukemia; Mixed Phenotype Acute Leukemia; Testicular Leukemia

• Registration Number: NCT03959085
• Lead Sponsor: Children's Oncology Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-5-20
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 4997

Inclusion Criteria

Inclusion Criteria:<br><br> - B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility<br> studies (Part A) prior to treatment and enrollment on AALL1732. Note that central<br> confirmation of MPAL diagnosis must occur within 22 days of enrollment for suspected<br> MPAL patients. If not performed within this time frame, patients will be taken off<br> protocol.<br><br> - APEC14B1 is not a requirement for B-LLy patients but for institutional compliance<br> every patient should be offered participation in APEC14B1. B-LLy patients may<br> directly enroll on AALL1732.<br><br> - Patients must be > 365 days and < 25 years of age<br><br> - White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior<br> to the start of protocol-directed systemic therapy):<br><br> - Age 1-9.99 years: WBC >= 50,000/uL<br><br> - Age 10-24.99 years: Any WBC<br><br> - Age 1-9.99 years: WBC < 50,000/uL with:<br><br> - Testicular leukemia<br><br> - CNS leukemia (CNS3)<br><br> - Steroid pretreatment.<br><br> - White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to<br> the start of protocol-directed systemic therapy):<br><br> - Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found<br> on central confirmatory testing to have B-ALL must meet the B-ALL criteria<br> above (age, WBC, extramedullary disease, steroid pretreatment) to switch to the<br> B-ALL stratum before the end of induction.<br><br> - Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016<br> criteria) with >= 25% blasts on a bone marrow (BM) aspirate;<br><br> - OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the<br> diagnosis can be established by a pathologic diagnosis of acute leukemia on a<br> BM biopsy;<br><br> - OR A complete blood count (CBC) documenting the presence of at least 1,000/uL<br> circulating leukemic cells if a bone marrow aspirate or biopsy cannot be<br> performed.<br><br> - Patient has newly diagnosed B-LLy Murphy stages III or IV.<br><br> - Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.<br><br> - Note: For B-LLy patients with tissue available for flow cytometry, the criterion for<br> diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e.,<br> paraffin blocks), the methodology and criteria for immunophenotypic analysis to<br> establish the diagnosis of B-LLy defined by the submitting institution will be<br> accepted.<br><br> - Central nervous system (CNS) status must be determined prior to enrollment based on<br> a sample obtained prior to administration of any systemic or intrathecal<br> chemotherapy, except for steroid pretreatment and cytoreduction. It is recommended<br> that intrathecal cytarabine be administered at the time of the diagnostic lumbar<br> puncture. This is usually done at the time of the diagnostic bone marrow or venous<br> line placement to avoid a second lumbar puncture. This is allowed prior to<br> enrollment. Systemic chemotherapy must begin within 72 hours of this intrathecal<br> therapy.<br><br> - All patients and/or their parents or legal guardians must sign a written informed<br> consent.<br><br> - All institutional, Food and Drug Administration (FDA), and NCI requirements for<br> human studies must be met.<br><br>Exclusion Criteria:<br><br> - Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL<br> are eligible for AALL1731, regardless of NCI risk group).<br><br> - With the exception of steroid pretreatment and steroid cytoreduction or the<br> administration of intrathecal cytarabine, patients must not have received any prior<br> cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any<br> cancer diagnosed prior to initiation of protocol therapy on AALL1732.<br><br> - Patients who have received > 72 hours of hydroxyurea within one week prior to start<br> of systemic protocol therapy.<br><br> - Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow<br> submitted for APEC14B1 testing and who do not have a peripheral blood sample<br> submitted containing > 1,000/uL circulating leukemia cells.<br><br> - Patients with acute undifferentiated leukemia (AUL) are not eligible.<br><br> - For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid<br> pretreatment, the following additional exclusion criteria apply:<br><br> - T-lymphoblastic lymphoma.<br><br> - Morphologically unclassifiable lymphoma.<br><br> - Absence of both B-cell and T-cell phenotype markers in a case submitted as<br> lymphoblastic lymphoma.<br><br> - Patients with known Charcot-Marie-Tooth disease.<br><br> - Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,<br> regardless of blast immunophenotype.<br><br> - Patients requiring radiation at diagnosis.<br><br> - Female patients who are pregnant, since fetal toxicities and teratogenic effects<br> have been noted for several of the study drugs. A pregnancy test is required for<br> female patients of childbearing potential.<br><br> - Lactating women who plan to breastfeed their infants while on study and for 2 months<br> after the last dose of inotuzumab ozogamicin.<br><br> - Sexually active patients of reproductive potential who have not agreed to use an<br> effective contraceptive method for the duration of study participation. For those<br> patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after<br> the last dose of inotuzumab ozogamicin for females and 5 months after the last dose<br> of inotuzumab ozogamicin for males.

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Improvement in 5-year disease-free survival (DFS)

Secondary Outcome Measures

Name	Time	Method
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;Incidence of adverse events for the integration of inotuzumab ozogamicin into the mBFM chemotherapy backbone in HR B-ALL;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 calapargase pegol;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;Overall survival (OS)