A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL)

RADIATION

3-Dimensional Conformal Radiation Therapy

Undergo 3D-CRT

DRUG

Asparaginase Erwinia chrysanthemi

Given IM

PROCEDURE

Biospecimen Collection

Undergo blood, urine and cerebrospinal fluid collection

BIOLOGICAL

Blinatumomab

Given IV

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

DRUG

Calaspargase Pegol

Given IV

DRUG

Cytarabine

Given IT

DRUG

Dexamethasone

Given PO or IV

DRUG

Hydrocortisone Sodium Succinate

Given IT

PROCEDURE

Lumbar Puncture

Undergo lumbar puncture

DRUG

Mercaptopurine

Given PO

DRUG

Methotrexate

Given IT, PO, and IV

BIOLOGICAL

Nivolumab

Given IV

DRUG

Pegaspargase

Given IM or IV

DRUG

Vincristine Sulfate

Given IV push or via infusion

Minimal residual disease (MRD) negative second remission (Rem-2) rate with blinatumomab vs with blinatumomab + nivolumab (Group 1)

Time frame: Up to 2 cycles of therapy (each cycle = 36 days)

MRD negative Rem-2 be defined as Rem-2 (i.e., achievement of MRD \< 1% blasts by flow cytometry and resolution of extramedullary disease (for CNS disease, requires CNS 1) ) and bone marrow with MRD \< 0.01% by flow cytometry. MRD negative Rem-2 rate between Arm A vs Arm B will be compared using a one-sided Z test of proportions with Type I error of 0.10. Interim analysis will be conducted to monitor for futility. The futility boundaries are based on testing the alternative hypothesis at the 0.067 level.

Event-free survival post-reinduction (EFS PR) (Group 3)

Time frame: From date of randomization to date of treatment failure, relapse, second malignancy (SMN) or death due to any cause, assessed up to 10 years after completion of enrollment.

Comparison of EFS post reinduction between Arm E versus Arm F will be based on a one-sided two-sample logrank test with Type I error of 0.10, to be conducted 3 years after completion of enrollment of Group 3. Interim analysis will be conducted to monitor for futility. The futility monitoring will be based on testing the alternative hypothesis at the 0.067 level. This alpha level corresponds to that which would cause futility stopping if the one-sided two-sample logrank test shows evidence of a hazard ratio \> 1.0 when half of the expected events are observed.

EFS PR (Group 4)

Time frame: From date of randomization to date of treatment failure, relapse, second malignancy (SMN) or death due to any cause, assessed up to 10 years after completion of enrollment.

Comparison of EFS post reinduction between Arm H versus Arm I will be based on a one-sided two-sample logrank test with Type I error of 0.10, to be conducted 3 years after completion of enrollment of Group 3. Interim analysis will be conducted to monitor for futility. The futility monitoring will be based on testing the alternative hypothesis at the 0.067 level. This alpha level corresponds to that which would cause futility stopping if the one-sided two-sample logrank test shows evidence of a hazard ratio \> 1.0 when half of the expected events are observed.

What is a clinical trial?

A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.

Is it safe to participate?

Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.

Will I be compensated?

Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.

Will I receive a placebo instead of treatment?

When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.

Can I leave a trial if I change my mind?

Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.

How long does a clinical trial last?

Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.