Pembrolizumab + Blinatumomab for Acute Lymphoblastic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: City of Hope Medical Center

Must not be taking: Antidepressants, Immunosuppressants

Disqualifiers: CNS disease, Organ transplantation, Autoimmune, 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: 30

Duration: 35-42 days per cycle, up to 5 cycles

36 Participants Needed

Trial Summary

What is the purpose of this trial?

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 leukemia that has come back or has not responded to the treatment. Monoclonal antibodies, such as pembrolizumab and blinatumomab, may interfere with the ability of tumor cells to grow and spread.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain cancer treatments before starting the study. You must stop chemotherapy, radiotherapy, tyrosine-kinase inhibitors, and immunotherapy at least 1 week or 5 half-lives before the study begins. Some maintenance medications for ALL, like glucocorticoids, can be taken up to 3 days before the study, but others like vinca alkaloids must be stopped 14 days prior.

What data supports the effectiveness of the drug pembrolizumab in treating cancer?

Pembrolizumab has been shown to improve survival in patients with certain types of lung cancer, as it helps the immune system attack cancer cells more effectively. It has been approved for use in advanced melanoma and non-small cell lung cancer, demonstrating significant improvements in survival compared to chemotherapy. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and Blinatumomab safe for humans?

Blinatumomab, used for certain types of leukemia, generally has a favorable safety profile, but it can cause side effects like cytokine-release syndrome (a reaction that can cause fever and low blood pressure) and neurological issues (like seizures), which are usually manageable with treatment. Pembrolizumab, used in various cancers, is also generally considered safe but can cause immune-related side effects. While specific safety data for the combination of these drugs is not provided, both have been used safely in humans for other conditions. ^{6 7 8 9 10}

How is the drug combination of Pembrolizumab and Blinatumomab unique for treating acute lymphoblastic leukemia?

This drug combination is unique because it combines Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with Blinatumomab, a bispecific T-cell engager that directs T-cells to target and destroy leukemia cells. This dual approach aims to enhance the immune response against leukemia, potentially offering a novel treatment option for patients who do not respond to standard therapies. ^{7 8 11 12 13}

Research Team

Lihua Budde

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for people with acute lymphoblastic leukemia that's come back or didn't respond to treatment. They must have had prior treatments, be relatively healthy and active (ECOG status 0-1), have good heart and lung function, normal kidney and liver tests, not pregnant or breastfeeding, no HIV/HBV/HCV infections, and willing to use contraception.

Inclusion Criteria

Ability to understand and sign informed consent form

My kidney function, measured by creatinine levels, is within the normal range.

Beta HCG negative

Exclusion Criteria

Concurrent participation in another investigational drug trial

Current participation in or recent completion of another investigational study

Psychiatric or substance abuse disorders

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab IV on day 15 of cycle 1 and days 1 and 22 of cycles 2-5, and blinatumomab IV on days 1-28. Treatment repeats every 35-42 days for up to 5 cycles.

35-42 days per cycle, up to 5 cycles

Optional Extension

Patients who achieve complete response have the option to receive blinatumomab IV for up to 4 additional cycles.

Up to 4 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

1 year

Follow-up at 30 days, then every 3 months

Treatment Details

Interventions

• Blinatumomab
• Pembrolizumab

Trial Overview The study is testing the effectiveness of two monoclonal antibodies—pembrolizumab and blinatumomab—in treating recurrent or unresponsive acute lymphoblastic leukemia. It aims to see how these drugs affect tumor growth.

Participant Groups

Group I: Treatment (pembrolizumab, blinatumomab) Experimental Treatment 3 Interventions

Participants receive pembrolizumab IV over 30 minutes on day 15 of course 1 and days 1 and 22 of courses 2 -4, and blinatumomab IV on days 1-28. Treatment repeats every 35-42 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

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?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

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]

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]

The maximum tolerated doses (MTDs) for the combination of pembrolizumab and trametinib were established, with concurrent dosing showing a lower objective response rate (0%) compared to intermittent dosing (27%).

While the combination treatment had manageable safety profiles, with 31% of patients experiencing grade 3/4 treatment-related adverse events in the concurrent group, the overall antitumor activity was limited, suggesting that this combination may not be highly effective for solid tumors and BRAF wild-type melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation. Maio, M., Carlino, MS., Joshua, AM., 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]

In a phase 3 clinical trial involving 669 patients aged 1 to 30 years with first relapse of B-cell acute lymphoblastic leukemia (B-ALL), substituting blinatumomab for intensive chemotherapy in consolidation therapy showed a 2-year disease-free survival rate of 54.4% compared to 39.0% for the chemotherapy group, suggesting a potential benefit of blinatumomab in this high-risk population.

Blinatumomab also demonstrated a better safety profile, with significantly lower rates of serious adverse events such as infections and febrile neutropenia compared to traditional chemotherapy, indicating it may be a safer option for treating relapsed B-ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. Brown, PA., Ji, L., Xu, X., et al.[2021]

Blinatumomab is a groundbreaking treatment for B-cell precursor relapsed/refractory acute lymphoblastic leukemia (ALL), showing the ability to induce deep remissions in some patients, but many still do not respond or relapse, highlighting the need for improved treatment strategies.

Understanding how patients respond or resist blinatumomab could help identify those who will benefit most, and combining it with other therapies or using it earlier in treatment protocols may enhance its effectiveness and reduce relapse rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific antibodies in acute lymphoblastic leukemia therapy. Chitadze, G., Laqua, A., Lettau, M., et al.[2021]

In a study of six children with relapsed/refractory acute lymphoblastic leukemia (R/R-ALL), blinatumomab demonstrated good short-term safety and effectiveness, with three children achieving complete remission after treatment.

Five out of six children experienced cytokine release syndrome (CRS), indicating a manageable side effect profile, and the overall survival rate was 41.7% with a median survival time of 126 days, suggesting potential for further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia]. Li, XL., Liu, LP., Liu, F., et al.[2023]

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]

Blinatumomab (Blincyto) received accelerated approval for treating B-cell precursor acute lymphoblastic leukemia (ALL) in patients with minimal residual disease, highlighting its efficacy in maintaining remission in both adults and children.

As a bispecific CD19-directed CD3 T-cell engager, blinatumomab works by activating T-cells to target and eliminate leukemia cells, demonstrating a novel mechanism of action in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A closer look at blinatumomab. Mattison, RJ.[2018]

In a study of 36 adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), blinatumomab treatment led to a high remission rate of 69%, with transient increases in liver enzymes and inflammatory markers that returned to baseline without clinical symptoms.

Patients who responded to blinatumomab exhibited significant T-cell expansion and specific immune responses, indicating that the drug effectively activates the immune system against leukemia cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL. Nägele, V., Kratzer, A., Zugmaier, G., et al.[2022]

In a study of 23 adults with B-cell acute lymphoblastic leukemia treated with blinatumomab, pre-emptive intravenous immune globulin (IVIG) did not reduce the incidence of hypogammaglobulinemia or associated infections compared to a control group.

Both groups experienced similar rates of infections and immunoglobulin levels, indicating that IVIG repletion may not be effective in mitigating the risks associated with blinatumomab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoglobulin repletion during blinatumomab therapy does not reduce the rate of secondary hypogammaglobulinemia and associated infectious risk. Wo, S., Levavi, H., Mascarenhas, J., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]

5. England pubmed.ncbi.nlm.nih.gov

KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Blinatumomab: A First-in-Class Bispecific T-Cell Engager for Precursor B-Cell Acute Lymphoblastic Leukemia. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Bispecific antibodies in acute lymphoblastic leukemia therapy. [2021]

9. China pubmed.ncbi.nlm.nih.gov

[Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia]. [2023]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Immunotargeting relapsed or refractory precursor B-cell acute lymphoblastic leukemia - role of blinatumomab. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

A closer look at blinatumomab. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL. [2022]

13. Korea (South) pubmed.ncbi.nlm.nih.gov

Immunoglobulin repletion during blinatumomab therapy does not reduce the rate of secondary hypogammaglobulinemia and associated infectious risk. [2022]