Blinatumomab + Nivolumab (+/- Ipilimumab) for Acute Lymphoblastic Leukemia

Not currently recruiting at 6 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anti-PD-1, Anti-CTLA-4

Disqualifiers: Active CNS leukemia, Autoimmune diseases, others

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

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

Compensation: Varies

Number of Visits: 9

Duration: 42 days per cycle, up to 5 cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and examine the side effects of a combination of treatments designed to help the immune system combat acute lymphoblastic leukemia, a type of blood cancer. The study focuses on using blinatumomab, nivolumab, and, for some patients, ipilimumab. These immunotherapy treatments help the body target and destroy cancer cells. The trial is specifically for individuals whose leukemia has returned after treatment or hasn't responded to treatment, particularly those with CD19+ leukemia. Those who have experienced a relapse, have not responded to past treatment, or have a new diagnosis of leukemia and are over 60 might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering a chance to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like chemotherapy, radiotherapy, or targeted therapy must be stopped a few weeks before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that combining blinatumomab with immune-boosting drugs like nivolumab and ipilimumab can be safe for patients with relapsed or hard-to-treat acute lymphoblastic leukemia. Studies have found that this combination is usually well-tolerated and yields promising results, such as significantly reducing cancer cells to undetectable levels.

Earlier studies reported some side effects, but these are often manageable. This drug combination has been tested before and can be used safely to treat this type of cancer. While this trial is in an early stage, focusing on finding the best dose and checking for side effects, existing evidence supports its potential safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Acute Lymphoblastic Leukemia (ALL) because they represent a different approach compared to traditional chemotherapy. Blinatumomab is a bispecific T-cell engager that helps the immune system target and kill cancer cells more efficiently. Nivolumab and ipilimumab are immune checkpoint inhibitors that boost the body's immune response against cancer cells, potentially leading to better outcomes. This combination aims to harness and enhance the body's natural defenses to fight leukemia, offering hope for patients who may not respond well to current treatments.

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

Research has shown that blinatumomab can improve outcomes for patients with relapsed or refractory CD19+ acute lymphoblastic leukemia (ALL) compared to standard chemotherapy. In this trial, participants will receive blinatumomab alongside nivolumab, with some also receiving ipilimumab. Early results suggest that combining blinatumomab with these immune-boosting drugs enhances effectiveness. Specifically, one study found that 72% of patients receiving this combination treatment did not experience cancer progression for at least 24 months, a significant improvement over the 14% with other treatments. These treatments help the immune system attack cancer cells, potentially preventing their growth and spread. ^{2 3 6 7 8}

Who Is on the Research Team?

Ivana Gojo

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for patients aged 16 or older with poor-risk CD19+ precursor B-lymphoblastic leukemia that's relapsed or refractory. It includes those over 60 who can't have standard treatment, and excludes pregnant women, breastfeeding mothers, and individuals with certain health conditions like uncontrolled illnesses or active CNS leukemia.

Inclusion Criteria

Adequate contraception agreement for women of child-bearing potential and men

Specific laboratory criteria including total bilirubin, AST/ALT, and serum creatinine or CrCl

My leukemia is Philadelphia chromosome positive.

Exclusion Criteria

I have lung disease that causes me symptoms.

I have a condition affecting my digestive system.

I have a diagnosed brain condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive blinatumomab IV continuously on days 1-28, with nivolumab IV on day 11 and every 2 weeks, and some receive ipilimumab IV on day 11 and every 6 weeks, for up to 5 cycles

42 days per cycle, up to 5 cycles

Continuous IV for blinatumomab, bi-weekly visits for nivolumab, and every 6 weeks for ipilimumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Ipilimumab
• Nivolumab

Trial Overview

The study tests the safety and optimal doses of blinatumomab combined with nivolumab alone or alongside ipilimumab in treating specific leukemia. These are immunotherapies designed to help the immune system fight cancer by targeting tumor cells' growth.

How Is the Trial Designed?

Group I: Treatment (blinatumomab, nivolumab, ipilimumab) Experimental Treatment 5 Interventions

Patients receive blinatumomab IV continuously on days 1-28. Treatment repeats every 42 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes on day 11 and then every 2 weeks for up to year. Some patients also receive ipilimumab IV over 90 minutes on day 11 and then every 6 weeks for up to 1 year. Patients also undergo bone marrow aspiration and biopsy and blood sample collection 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+

Published Research Related to This Trial

Blinatumomab is a promising new treatment for adults with relapsed or refractory B-cell acute lymphoblastic leukemia, showing effectiveness in targeting and destroying tumor cells by engaging both T-cells and B-cells.

While there are potential side effects like immunological toxicities and cytokine release syndrome, most patients tolerate blinatumomab well, indicating a favorable safety profile compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults. Lee, KJ., Chow, V., Weissman, A., et al.[2022]

Blinatumomab shows a favorable safety profile in pediatric patients with B-cell acute lymphoblastic leukemia (ALL), associated with a lower risk of serious adverse events, febrile neutropenia, and infections compared to traditional chemotherapy.

While blinatumomab does not significantly increase the risk of cytokine release syndrome or seizures, it is linked to a higher risk of encephalopathy, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. Marrapodi, MM., Mascolo, A., di Mauro, G., et al.[2022]

Blinatumomab, a bispecific T-cell-engaging antibody, has shown a response rate of 34% to 66% in heavily pretreated children with relapsed/refractory acute lymphoblastic leukemia (R/R-ALL), making it a promising treatment option, especially as a bridge to stem cell transplantation.

Recent randomized controlled trials indicate that blinatumomab leads to a greater reduction in minimal residual disease and improved survival compared to standard treatments, suggesting its potential for frontline use in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab in Pediatric Acute Lymphoblastic Leukemia-From Salvage to First Line Therapy (A Systematic Review). Queudeville, M., Ebinger, M.[2021]

In a study of 20 patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) treated with blinatumomab, 20% experienced extramedullary relapse, indicating a significant concern for this type of relapse after treatment.

The median time to extramedullary relapse was 179 days, with relapses occurring in various organs, suggesting that while blinatumomab is effective, there is a need for further research to prevent these relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of relapse patterns in patients with acute lymphoblastic leukemia treated with blinatumomab. Lau, KM., Saunders, IM., Goodman, AM.[2021]

Nivolumab combined with ipilimumab significantly improves overall survival in adult patients with intermediate/poor-risk advanced renal cell carcinoma compared to sunitinib, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

In the study involving 1096 patients, the median overall survival was not reached for the nivolumab + ipilimumab group, while it was 25.95 months for the sunitinib group, highlighting the potential of this combination therapy for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Medicines Agency extension of indication to include the combination immunotherapy cancer drug treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) for adults with intermediate/poor-risk advanced renal cell carcinoma. Ali, S., Camarero, J., Hennik, P., et al.[2021]

In a phase 2 study, blinatumomab demonstrated a significant overall survival benefit for patients with relapsed/refractory Ph(-) B-precursor acute lymphoblastic leukemia, with a mean survival of 76.1 months compared to 39.8 months for historical patients receiving standard chemotherapy.

At 60 months, 12.6% of patients treated with blinatumomab were still alive, which is more than double the 5.4% survival rate of historical controls, indicating its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data. Barlev, A., Lin, VW., Katz, A., et al.[2021]

Blinatumomab, a bispecific T-cell engager, shows significant efficacy in treating refractory or relapsed acute lymphoblastic leukemia (ALL), achieving complete response rates of 39% to 69% and a median overall survival of 7.7 months, compared to 4.0 months with traditional chemotherapy.

The treatment has a favorable safety profile, with manageable side effects such as cytokine-release syndrome and reversible neurological issues, making it a promising option for both adult and pediatric patients with R/R ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotargeting relapsed or refractory precursor B-cell acute lymphoblastic leukemia - role of blinatumomab. Queudeville, M., Handgretinger, R., Ebinger, M.[2020]

PD-1/PD-L1 inhibitors have limited effectiveness in patients with low PD-L1 expression in advanced non-small cell lung cancer (NSCLC), highlighting the need for improved treatment options.

Dual immunotherapy, combining PD-1 and CTLA-4 inhibitors, shows promise for better long-term survival in NSCLC, with ongoing research focused on identifying optimal patient groups and ensuring safety through multidisciplinary approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dual Immunotherapy in Advanced Non-small Cell Lung Cancer: the Progress and Clinical Application]. Deng, H., Wang, L., Yang, Y., et al.[2022]

Blinatumomab is a first-in-class bispecific T-cell engager that effectively targets both CD19 on B-cells and CD3 on T-cells, showing a high response rate of 43% for complete remission in patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia (B-ALL).

Patients treated with blinatumomab had a median overall survival of 6.1 months and 60% achieved minimal residual disease negativity, although common side effects included fever, neurological events, and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: A First-in-Class Bispecific T-Cell Engager for Precursor B-Cell Acute Lymphoblastic Leukemia. Buie, LW., Pecoraro, JJ., Horvat, TZ., et al.[2018]

Blinatumomab represents a significant advancement in immunotherapy for relapsed or refractory acute lymphoblastic leukemia (ALL), demonstrating unprecedented efficacy by stimulating a strong T-cell response, which is a departure from traditional chemotherapy.

While blinatumomab offers promising benefits, it also presents unique immunological toxicities and complex administration requirements, necessitating careful consideration of its use compared to other emerging therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies. Rogala, B., Freyer, CW., Ontiveros, EP., et al.[2023]

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.

These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. Kahl, KL.[2021]

Two cases of patients with multiple in-transit metastatic melanomas were successfully treated using intensity-modulated radiotherapy (IMRT) combined with immune checkpoint inhibitors ipilimumab or nivolumab.

The combination of IMRT and immune checkpoint inhibitors suggests a potential enhancement of antitumor effects, indicating a promising approach for improving treatment outcomes in melanoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of multiple in-transit melanomas on the leg with intensity-modulated radiotherapy and immune checkpoint inhibitors: Report of two cases. Fujimura, T., Kambayashi, Y., Furudate, S., et al.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12235782/

One step further in targeting acute leukemia by combining ...

This review focuses on antibody-based targeted treatments, which so far, have been shown to improve the treatment outcomes.

2.

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 ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0006497123055702

Blinatumomab in Combination with Immune Checkpoint ...

We describe results of a multi-center phase I study combining blina with immune checkpoint inhibitors (ICIs) targeting PD-1 (nivolumab) +/- CTLA-4 (ipilimumab).

4.

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 ...

5.

nature.com

nature.com/articles/s41571-024-00981-0.pdf

Research highlights

At a median follow-up duration of. 31.5 months, patients in the ipilimumab– nivolumab group had a 24-month PFS of 72% versus 14% (adjusted difference in mean.

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/PMC6833142/

Recent advances on blinatumomab for acute lymphoblastic ...

This review summarized data from recent clinical trials of blinatumomab for B-ALL treatment. Keywords: Acute lymphoblastic leukemia, ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S2531137923001487

Review article All about blinatumomab: the bispecific T cell ...

B cell acute lymphoblastic leukemia-lymphoma (B-ALL) accounts for approximately 75% of ALL cases and is observed in children and adults.