RecruitingB Acute Lymphoblastic LeukemiaB Lymphoblastic LymphomaCentral Nervous System Leukemia

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

Eligible age

0–25 yrs

Accepts

All genders

Locations

49 states

Healthy volunteers

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About this study

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.

Sponsor: Children's Oncology Group

You may qualify if…

✓ 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

You may not qualify if…

✕ 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.