IRB Study Number 19-1540
Status Recruiting
Phase Phase 3
Institutes Taussig Cancer Institute, Pediatric Institute
Description
Primary Objective
To determine in a randomized manner if the addition of 2 blocks of inotuzumab ozogamicin to modified Berlin-Frankfurt-Münster (mBFM) chemotherapy will improve 5-year disease-free survival (DFS) in children and young adults with High-Risk (HR) B-cell acute lymphoblastic leukemia (B-ALL).
Secondary Objectives
1.2.1 To describe the 5-year DFS for a favorable risk subset of 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.
1.2.2 To determine the toxicity and tolerability of inotuzumab ozogamicin integrated into the mBFM chemotherapy backbone in HR B-ALL.
1.2.3 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 escalating intravenous (IV) methotrexate (MTX) without leucovorin rescue plus pegaspargase (C-MTX).
1.2.4 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.
Inclusion Criteria
3.2.1 Eligibility Screening
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 7 business days after enrollment for MPAL patients. If not performed within this time frame, patients will be taken off protocol. See Section 3.1.4 for timing details.
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 and MUST submit eligibility studies as outlined in Section 13.0.
3.2.2 Age at diagnosis
Patients must be > 365 days and < 25 years of age
3.2.3 White Blood Cell Count (WBC) Criteria
White Blood Cell Count (WBC) Criteria for patients with B-ALL
Age 1-9.99 years: WBC ≥ 50,000/μL
Age 10-24.99 years: Any WBC
Age 1-9.99 years: WBC < 50,000/μL with:
o Testicular leukemia
o CNS leukemia (CNS3)
o Steroid pretreatment (see Section 3.3.3)
White Blood Cell Count (WBC) Criteria for patients with MPAL
Age 1-24.99 years: any WBC
3.2.4 Diagnosis
Patient has newly diagnosed B-ALL or MPAL (by WHO2016 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/μL circulating leukemic cells if a bone marrow aspirate or biopsy cannot be performed;
OR Patient has newly diagnosed B-LLy Murphy Stages III or IV (See Appendix VII for staging);
OR Patient has newly diagnosed B-LLy Murphy Stages I or II with steroid pretreatment (See Section 3.3.3 for steroid pretreatment details).
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.
Exclusion Criteria
3.2.5.1 Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL are eligible for AALL1731, regardless of NCI risk group).
3.2.5.2 Patients with known Charcot-Marie-Tooth disease.
3.2.5.3 Prior Therapy
With the exception of steroid pretreatment (defined in Section 3.3.3) 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.
3.2.5.4 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/μL circulating leukemia cells.
3.2.5.5 Patients with Acute Undifferentiated Leukemia (AUL) are not eligible.
3.2.5.6 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.
3.2.5.7 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.
3.2.5.8 Lactating women who plan to breastfeed their infants while on study and for 2 months after the last dose of inotuzumab ozogamicin.
3.2.5.9 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.
