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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

365 Days - 25 Years

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Blinatumomab — BIOLOGICAL
  Given IV
• Bone Marrow Aspiration — PROCEDURE
  Undergo bone marrow aspiration
• Bone Marrow Biopsy — PROCEDURE
  Undergo bone marrow biopsy
• Bone Scan — PROCEDURE
  Undergo bone scan
• Calaspargase Pegol — DRUG
  Given IV
• Computed Tomography — PROCEDURE
  Undergo CT
• Cyclophosphamide — DRUG
  Given IV
• Cytarabine — DRUG
  Given IV, IT, or SC
• Daunorubicin Hydrochloride — DRUG
  Given IV
• Dexamethasone — DRUG
  Given PO or IV
• Doxorubicin Hydrochloride — DRUG
  Given IV
• Inotuzumab Ozogamicin — BIOLOGICAL
  Given IV
• Leucovorin Calcium — DRUG
  Given PO or IV
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Mercaptopurine — DRUG
  Given PO
• Methotrexate — DRUG
  Given IT or IV
• Pegaspargase — DRUG
  Given IV or IM
• Positron Emission Tomography — PROCEDURE
  Undergo PET
• Prednisolone — DRUG
  Given PO or IV
• Prednisone — DRUG
  Given PO or IV
• Questionnaire Administration — OTHER
  Ancillary studies
• Radiation Therapy — RADIATION
  Undergo testicular radiation therapy
• Radiation Therapy — RADIATION
  Undergo cranial radiation therapy
• Thioguanine — DRUG
  Given PO
• Vincristine Sulfate — DRUG
  Given IV

Study Details

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.

Key Dates

Start date

Oct 31, 2019

Status verified

Mar 2026

Primary completion

Mar 31, 2032

Completion

Mar 31, 2032

Study Design

Enrollment

5,951 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Arm D (CD 22 positive HR B-ALL)
  See detailed description for Arm D
• Experimental: Arm E (CD22 positive HR B-ALL)
  See detailed description for Arm E.
• Experimental: Arm I (MPAL)
  See Detailed Description for Arm I.
• Experimental: Arm II (B-LLy)
  See Detailed Description for Arm II.

Primary Outcome Measure

Post-induction 5-year event-free survival (EFS) [ Time Frame: From study entry to first event (induction failure, induction death, end of induction [EOI] minimal residual disease [MRD] ≥ 5%,EO consolidation [C] MRD ≥ 0.01%, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years ]

Locations (203)

Find similar trials in Birmingham, AL

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