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

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.

Conditions

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

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

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Children's Oncology Group

  lead NETWORK

Principal Investigators

• Jennifer L McNeer · Children's Oncology Group

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

365 Days

Max Age

25 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-10-31

Primary Completion

2032-03-31

Completion

2032-03-31

FDA Drug

Yes

Countries

• United States
• Australia
• Canada
• New Zealand
• Puerto Rico

Study Locations