Blinatumomab + Pembrolizumab for Leukemia

No longer recruiting at 3 trial locations

Overseen By Jesika Reiner, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Diego

Must not be taking: Checkpoint inhibitors, GM-CSF, G-CSF

Disqualifiers: CNS involvement, HIV, Hepatitis, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding pembrolizumab, an immunotherapy drug, to the existing treatment, blinatumomab, improves outcomes for adults with B-lineage acute lymphoblastic leukemia (B-ALL) that has returned or not responded to prior treatments. Researchers aim to determine if this combination leads to better remission rates compared to blinatumomab alone. Suitable candidates are those who have received at least one previous treatment for B-ALL and have a high percentage of leukemia cells in their bone marrow. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received chemotherapy or radiotherapy within 2 weeks before starting the study, and certain medications like GM-CSF or G-CSF cannot be used within 2 weeks of the study treatment.

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

Research has shown that combining blinatumomab and pembrolizumab is generally safe for adults with relapsed or hard-to-treat B-lineage acute lymphoblastic leukemia (B-ALL). Studies have found that patients usually tolerate this treatment well. Some side effects can occur, but they are often manageable. Common side effects include fatigue, fever, and headaches, while serious side effects are less common.

Although this treatment remains under study, the results so far are promising for those considering joining a trial. It is important to discuss potential risks and benefits with a doctor before making a decision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Blinatumomab and Pembrolizumab for leukemia because of their unique mechanisms of action. Blinatumomab is a bispecific T-cell engager that connects T-cells to cancer cells, encouraging the immune system to attack the leukemia cells directly. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that helps T-cells remain active in fighting cancer by blocking the PD-1 pathway, which often allows cancer cells to evade an immune response. This combination has the potential to create a more robust immune attack against leukemia cells than current treatments like chemotherapy or single-agent immunotherapies. By working together, these drugs could enhance the immune system’s ability to target and destroy cancer cells more effectively.

What evidence suggests that this trial's treatments could be effective for B-ALL?

Research shows that combining blinatumomab with pembrolizumab may offer promise for treating B-cell acute lymphoblastic leukemia (B-ALL). In one study, this combination achieved a high success rate, with 79% of patients showing no signs of leukemia after treatment, even if their blood counts had not fully normalized. Blinatumomab alone has proven effective for B-ALL, with some studies reporting a 30% response rate within 12 weeks. Pembrolizumab, a drug that aids the immune system in fighting cancer, might enhance treatment outcomes when added to blinatumomab. This trial specifically examines the combination of blinatumomab and pembrolizumab to determine its effectiveness for patients whose B-ALL has returned or is difficult to treat. ^{1 2 3 4 6}

Who Is on the Research Team?

James K Mangan, M.D., P.h.D.

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

Adults with relapsed or refractory B-cell acute lymphoblastic leukemia who have tried at least one therapy before can join. They must not be pregnant, agree to use birth control, and should not have had certain treatments or surgeries recently. People with heart issues, other cancers needing treatment, active infections like TB or hepatitis, HIV, recent vaccines, autoimmune diseases or lung problems are excluded.

Inclusion Criteria

My organs are working well.

I agree to use two forms of birth control or abstain from sex during and up to 120 days after the study.

I agree to use a condom during sex with women who can have children, from the start of the study until 120 days after it ends.

Exclusion Criteria

I had a stem cell transplant from a donor within the last 5 years.

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment

I have been diagnosed with Burkitt lymphoma/leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive blinatumomab and pembrolizumab. Blinatumomab is administered as a continuous IV infusion for 28 days per cycle, and pembrolizumab is given as an IV infusion on Days 15 and 36 of each cycle.

28 weeks

Multiple visits for IV infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Pembrolizumab

Trial Overview The trial is testing if adding pembrolizumab to blinatumomab improves response in patients whose leukemia has returned after treatment or didn't respond to previous therapies. It's a two-part study: first part checks safety (Phase I) and second part measures effectiveness (Phase II).

How Is the Trial Designed?

Group I: Blinatumomab + Pembrolizumab Experimental Treatment 2 Interventions

Drug: blinatumomab Cycle 1 Blinatumomab Day 1-7 Continuous IV infusion for 28 days (9 mcg/day) Blinatumomab Day 8-28 Continuous IV infusion for 28 days (28 mcg/day) Cycle 2-5 Blinatumomab Day 1-28 Continuous IV infusion for 28 days (28 mcg/day) Cycle length 42 days Other Names: Blincyto Drug: pembrolizumab Cycle 1 Pembrolizumab Day 15 and 36 IV infusion over 30 minutes (200mg) Cycle 2-5 Pembrolizumab Day 15 and 36 IV infusion over 30 minutes (200mg) Other Names: * Keytruda * MK-3475

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?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Matthew Wieduwilt, M.D., Ph.D.

Lead Sponsor

Trials

1

Recruited

20+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Pembrolizumab is an effective cancer treatment that works by reactivating T cells, but it can lead to various immune-related adverse events, including rare cases of synovitis.

Healthcare providers should be vigilant about the potential for pembrolizumab-induced synovitis and act quickly to treat it to prevent lasting joint damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Could knee inflammatory synovitis be induced by pembrolizumab? Mahmoud, F., Wilkinson, JT., Gizinski, A., et al.[2018]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

Pembrolizumab combined with adjuvant chemotherapy significantly improves one-year survival rates, overall response rates, and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC), based on a meta-analysis of 14 studies.

This treatment not only enhances efficacy but also reduces the incidence of adverse drug reactions, indicating a favorable safety profile, although further validation through larger randomized controlled trials is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Guo, WW., Zhang, TW., Wang, BL., et al.[2023]

In a study of 550 patients with advanced non-small-cell lung cancer, pembrolizumab demonstrated a 41% objective response rate in treatment-naive patients and a 23% response rate in previously treated patients, indicating its efficacy as a treatment option.

The median overall survival was significantly longer for treatment-naive patients (22.3 months) compared to previously treated patients (10.5 months), with safety data showing that only 12% experienced grade 3-5 treatment-related adverse events, suggesting a tolerable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with advanced non-small-cell lung cancer (KEYNOTE-001): 3-year results from an open-label, phase 1 study. Leighl, NB., Hellmann, MD., Hui, R., et al.[2022]

Pembrolizumab monotherapy significantly improved quality-adjusted survival (Q-TWiST) by 2.49 months compared to platinum-based chemotherapy and by 2.29 months compared to docetaxel in patients with advanced non-small cell lung cancer, indicating its efficacy in enhancing patient quality of life.

The benefits of pembrolizumab continued to increase over time, suggesting that it not only offers longer overall survival but also fewer treatment-related adverse events compared to traditional chemotherapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Q-TWiST Analysis to Assess Benefit-Risk of Pembrolizumab in Patients with PD-L1-Positive Advanced or Metastatic Non-small Cell Lung Cancer. Huang, M., Pietanza, MC., Samkari, A., et al.[2020]

In a study of 59 patients with relapsed/refractory extranodal natural killer/T-cell lymphoma treated with pembrolizumab, the overall response rate was 40.7%, with 28.8% achieving a complete response, indicating its potential efficacy as a salvage therapy.

While pembrolizumab showed modest effectiveness, it was associated with some grade 3 or 4 adverse events in 20.3% of patients, with neutropenia being the most common, suggesting that while it can be beneficial, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. Lee, JY., Kwon, JH., Hur, JY., et al.[2023]

In a study of patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab, a higher overall tumor burden was associated with a lower incidence of severe immune-related adverse events (irAEs), suggesting that tumor size may influence treatment safety.

Good performance status and high PD-L1 expression were significant predictors of developing severe irAEs, with odds ratios of 3.27 and 4.44, respectively, indicating that patients with these characteristics should be closely monitored during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk factors for severe immune-related adverse events after first-line pembrolizumab monotherapy or combination chemotherapy for non-small-cell lung cancer. Sumi, T., Koshshino, Y., Sekikawa, M., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, has demonstrated significant efficacy in reducing tumor size and improving survival rates in patients with non-small cell lung carcinoma (NSCLC).

However, the treatment is associated with an increased risk of immune-related adverse effects, including cases of type 1 diabetes mellitus and autoimmune thyroiditis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: An Immunotherapeutic Agent Causing Endocrinopathies. Chaudry, A., Chaudry, M., Aslam, J.[2020]

Pembrolizumab is a safe and effective immune checkpoint inhibitor that targets the PD-1 receptor, currently approved for treating advanced melanoma and metastatic non-small cell lung cancer (NSCLC).

Ongoing studies are exploring the potential of pembrolizumab in combination with other treatments for lung cancer and other cancer types, while also investigating biomarkers that may predict patient response to this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Dang, TO., Ogunniyi, A., Barbee, MS., et al.[2020]

In a phase 1b study involving 28 patients with myelodysplastic syndromes (MDS) resistant to hypomethylating agents, pembrolizumab demonstrated manageable safety, with 36% experiencing treatment-related adverse events, but no patients achieved a complete or partial response.

Despite the lack of significant tumor response, 19% of patients showed a complete response in bone marrow, and the median overall survival was 6 months, indicating some clinical activity in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study. Garcia-Manero, G., Ribrag, V., Zhang, Y., et al.[2022]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

A phase I study found that the combination of utomilumab, an investigational antibody targeting CD137, and pembrolizumab is safe and well tolerated in patients with various solid cancers.

This combination therapy resulted in sustained responses, suggesting potential efficacy in treating these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing PD-1 Blockade in Solid Tumors. [2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03160079

Study Details | NCT03160079 | Blinatumomab and ... The primary objective of this study is to determine if the addition of pembrolizumab to blinatumomab improves the Complete Response Rate (CR) and Complete ...

2. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/8985/492655/Interim-Results-of-a-Phase-1-2-Study-of

Interim Results of a Phase 1/2 Study of Pembrolizumab ... Encouraging anti-leukemic activity has been seen in the majority of treated patients (CR+CRi rate of 79%) and most CR are MRD negative, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11164718/

Real-world evidence on treatment pattern, effectiveness, and ... Blinatumomab is efficacious in patients with B-cell acute lymphoblastic leukemia (B-ALL), yet limited real-world data exists in this context.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e19584

Results from a phase 1b study of blinatumomab ... In cohort 2a, the objective response rate within 12 weeks of blinatumomab treatment was 30%; the median duration of response in responders (n = ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03512405

Pembrolizumab and Blinatumomab in Treating Participants ... This phase I/II studies the side effects of pembrolizumab and blinatumomab and to see how well they work in treating participants with acute lymphoblastic ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT258349

A phase I/II study of blinatumomab in combination with ... Background: Outcomes for adults with relapsed/refractory B-cell ALL (R/R B-ALL) remain poor despite new targeted therapies. Blinatumomab is an anti-CD19/CD3 ...