Blinatumomab + Nivolumab for Acute Lymphoblastic Leukemia

Recruiting at 179 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Disqualifiers: B-LLy, Burkitt leukemia, Ph+ B-ALL, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 10-12 weeks

461 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining two treatments, blinatumomab and nivolumab, is more effective than using blinatumomab alone for individuals with relapsed B-cell acute lymphoblastic leukemia (B-ALL). Blinatumomab (Blincyto) targets and attaches to cancer cells to trigger an immune response, while nivolumab (Opdivo) may enhance the immune system's ability to fight cancer. Individuals with a recurrence of B-ALL, whether in the bone marrow or other areas like the central nervous system or testes, may qualify for this study. The trial also includes individuals with Down syndrome who have relapsed B-ALL. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there are specific guidelines for certain treatments, like a 24-hour 'washout' period (time without taking certain medications) for some patients with Down syndrome before starting immunotherapy. It's best to discuss your current medications with the trial team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using blinatumomab and nivolumab together is generally safe for patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL). Blinatumomab helps the immune system find and attack cancer cells. Many patients have responded well to this treatment.

When these two drugs are combined, some side effects can occur. Although serious side effects have been observed, most patients manage the treatment well, and the benefits often outweigh the risks. This combination therapy can be administered without major problems.

Prospective trial participants should know that safety and side effects are closely monitored to address any serious issues promptly. While no treatment is without risks, current evidence suggests that this combination is a promising option for those with relapsed B-ALL. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using blinatumomab and nivolumab for acute lymphoblastic leukemia (ALL) because these drugs bring innovative approaches to treatment. Blinatumomab is a bispecific T-cell engager (BiTE) that helps the immune system target and destroy cancer cells more effectively. Unlike traditional chemotherapy drugs that attack both healthy and cancerous cells, blinatumomab specifically directs the body's own T-cells to attack only the leukemia cells. Nivolumab, on the other hand, is an immune checkpoint inhibitor that enhances the immune system's ability to fight cancer by preventing cancer cells from deactivating immune responses. Together, these drugs offer a targeted and potentially more effective approach compared to standard chemotherapy, with the promise of fewer side effects.

What evidence suggests that this trial's treatments could be effective for B-cell acute lymphoblastic leukemia?

Research has shown that blinatumomab effectively treats relapsed B-cell acute lymphoblastic leukemia (B-ALL), particularly in children and young adults. It helps the body's T cells attack cancer cells. Studies have found that it leads to better outcomes than traditional chemotherapy. In this trial, some participants will receive blinatumomab combined with nivolumab, which strengthens the immune system. Using nivolumab with blinatumomab might enhance the fight against leukemia. Early evidence suggests that this combination could halt cancer growth and reduce symptoms. These findings offer hope for improved treatment options for those with relapsed B-ALL. ^{2 6 7 8 9}

Who Is on the Research Team?

Stacy L Cooper

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for patients aged 1 to 30 with B-cell acute lymphoblastic leukemia that has relapsed. It includes those with Down syndrome and isolated or combined bone marrow, CNS (excluding optic nerve/retinal and CNS chloromas), or testicular relapse. Participants must have an ECOG score of 0-2, indicating they can perform daily activities, and must have recovered from previous treatments' side effects.

Inclusion Criteria

I can care for myself but may not be able to do active work.

My ability to perform daily activities is rated as ECOG 0-2, even with a developmental delay.

I have recovered from side effects of my previous cancer treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Immunotherapy Treatment

Patients receive methotrexate, cytarabine, or intrathecal triple therapy, along with dexamethasone and vincristine sulfate. Additional treatments for specific conditions like CNS or testicular disease.

1-3 weeks

Treatment

Patients receive blinatumomab and nivolumab, with cycles repeating every 36-37 days for up to 2 cycles. Treatment includes dexamethasone, methotrexate, and other supportive therapies.

10-12 weeks

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

12 months

Follow-up visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Nivolumab

Trial Overview The study compares the effectiveness of Blinatumomab alone versus in combination with Nivolumab in treating relapsed B-ALL. Blinatumomab targets cancer cells for immune destruction while Nivolumab aims to boost the immune system's response against cancer.

How Is the Trial Designed?

Group I: Group 4, Arm H (dexamethasone blinatumomab) Experimental Treatment 9 Interventions

Patients receive dexamethasone PO or IV on day 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28 and MTX IT on days 1 of cycle 1 only and days 15 and 36 ( for patients with CNS1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle). Cycles repeat every 37 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study.

Group II: Group 4 Arm I (Dexamethasone, blinatumomab, nivolumab) Experimental Treatment 11 Interventions

Patients receive dexamethasone PO or IV on day 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV, over 30 minutes on day 11 of cycle 1 and day 3 of cycle 2 and MTX IT on days 1 of cycle 1 only and days 15 and 36 ( for patients with CNS1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle). Cycles repeat every 37 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study.

Group III: Group 3, Arm F (dexamethasone, blinatumomab, nivolumab) Experimental Treatment 16 Interventions

See Outline section

Group IV: Group 3, Arm E (dexamethasone, blinatumomab, MTX) Experimental Treatment 15 Interventions

See Outline section

Group V: Group 2, Arm D (dexamethasone, nivolumab, blinatumomab, MTX) Experimental Treatment 8 Interventions

Patients receive dexamethasone, blinatumomab, and MTX as in Arm C. Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD \< 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD \>= 0.01% after cycle 1 proceed to cycle 2. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study. (CLOSED TO ACCRUAL 9/19/2024)

Group VI: Group 2, Arm C (dexamethasone, blinatumomab, MTX) Experimental Treatment 7 Interventions

Patients receive dexamethasone PO or IV on day 1 of cycle 1, blinatumomab via continuous IV infusion on days 1-28 of cycles 1 and 2, and methotrexate IT on days 1 and 15 of cycles 1 and 2 (day 1 may be omitted from cycle 1 if intrathecal therapy is given \< 7 days prior to the start of this cycle). Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD \< 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD \>= 0.01% after cycle 1 proceed to cycle 2. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study. (CLOSED TO ACCRUAL 9/19/2024)

Group VII: Group 1, Arm B (dexamethasone, blinatumomab, MTX) Experimental Treatment 10 Interventions

Patients receive dexamethasone, blinatumomab, and MTX, cytarabine, or ITT as in Arm A. Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD \< 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD \>= 0.01% after cycle 1 proceed to cycle 2. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study. (CLOSED TO ACCRUAL 9/19/2024)

Group VIII: Group 1, Arm A (dexamethasone, blinatumomab, MTX) Experimental Treatment 9 Interventions

ARM A: Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1, blinatumomab via continuous IV infusion on days 1-28 of cycles 1-2, MTX IT, cytarabine IT, or ITT IT on days 1, 15, and 36 of cycle 1 (MTX, cytarabine, and ITT on day 1 may be omitted if intrathecal therapy was given \< 7 days prior to the start of this cycle), and MTX IT, cytarabine IT, or ITT IT on days 15 and 36 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD \< 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD \>= 0.01% after cycle 1 proceed to cycle 2. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study. (CLOSED TO ACCRUAL 9/19/2024)

Group IX: Arm G (dexamethasone, blinatumomab, nivolumab,MTX) DS patients Experimental Treatment 10 Interventions

Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 11 of cycle 1 and day 3 of cycle 2, and MTX IT (for patients with CNS1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle). Cycles repeat every 37 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study.

Blinatumomab is already approved in European Union, United States for the following indications:

Approved in European Union as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• High-risk first relapse BCP-ALL

Approved in United States as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• First or second complete remission with minimal residual disease (MRD)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04546399

NCT04546399 | A Study to Compare Blinatumomab Alone ... This phase II trial studies the effect of nivolumab in combination with blinatumomab compared to blinatumomab alone in treating patients with B-cell acute ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6173178/

Impact of blinatumomab on patient outcomes in relapsed ... This review summarizes the current and future data with blinatumomab in R/R B-cell ALL in the adult and pediatric population. Keywords: acute lymphoblastic ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/966/499579/Blinatumomab-in-Combination-with-Immune-Checkpoint

Blinatumomab in Combination with Immune Checkpoint ... Background: Blinatumomab (blina) improves outcomes in R/R CD19+ ALL compared to chemotherapy. However, the overall response rate to blina ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2531137923001487

Review article All about blinatumomab: the bispecific T cell ... Blinatumomab is a bispecific T cell engager containing the CD3 and CD19 that recognize domains redirecting cytotoxic T cells to lyse B cells.

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2021/blinatumomab-relapsed-b-cell-leukemia-children-young-adults

Blinatumomab Effective for Children with Relapsed Leukemia The immunotherapy drug blinatumomab (Blincyto) is more effective than chemotherapy in treating B-cell acute lymphoblastic leukemia (B-ALL) that has relapsed in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02879695

NCT02879695 | Blinatumomab and Nivolumab With or ... This phase I trial studies the side effects and best dose of blinatumomab when given with nivolumab alone or nivolumab and ipilimumab in treating patients ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6605719/

Blinatumomab, a bispecific B-cell and T-cell engaging ... Clinical trials have demonstrated its efficacy in relapsed B-cell Acute Lymphoblastic Leukaemia (B-ALL) and B-cell Non-Hodgkin's Lymphoma including in patients ...

8. uchicagomedicine.org uchicagomedicine.org/find-a-clinical-trial/clinical-trial/cirb210060

CLINICAL TRIAL / NCT04546399 This phase II trial studies the effect of nivolumab in combination with blinatumomab compared to blinatumomab alone in treating patients with B-cell acute ...

9. withpower.com withpower.com/trial/phase-1-leukemia-2021-9fc02

Blinatumomab for Acute Lymphoblastic Leukemia Grade 3 or 4 adverse effects are common. Despite these risks, most patients tolerate the therapy relatively well. Safety data has been evaluated in both ...