Azacitidine + Pembrolizumab for Hodgkin's Lymphoma

Recruiting in Palo Alto (17 mi)

Overseen by David McCall, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Uncontrolled infection, Hypertension, Heart failure, HIV, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study is a Phase II single-center clinical trial designed to assess the efficacy, safety, and tolerability of pembrolizumab in combination with the 7-day regimen of azacitidine for the treatment of relapsed/refractory HL.

Will I have to stop taking my current medications?

The trial requires that you stop using immunosuppressive medications 14 days before starting pembrolizumab, with some exceptions like certain steroids. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Azacitidine + Pembrolizumab for Hodgkin's Lymphoma?

Research shows that Pembrolizumab, one of the drugs in the treatment, has a high response rate in patients with relapsed or refractory classic Hodgkin lymphoma, with a 69% overall response rate. Additionally, Pembrolizumab has been effective in combination with other treatments for Hodgkin lymphoma, achieving complete metabolic responses in many patients. ^{1 2 3 4 5}

Is the combination of Azacitidine and Pembrolizumab safe for humans?

Pembrolizumab has been studied in various conditions and generally shows a favorable safety profile, though some patients experience serious side effects like immune-related reactions and infections. In studies with Hodgkin's lymphoma, common side effects included febrile neutropenia (fever with low white blood cell count) and liver enzyme elevations. Azacitidine, under different names, is also used in treatments but specific safety data for its combination with Pembrolizumab in Hodgkin's lymphoma is not detailed in the provided research. ^{3 6 7 8 9}

How is the drug combination of Azacitidine and Pembrolizumab unique for treating Hodgkin's Lymphoma?

The combination of Azacitidine and Pembrolizumab is unique because Azacitidine may enhance the immune response by priming the immune system, potentially increasing the effectiveness of Pembrolizumab, an immune checkpoint inhibitor, in treating relapsed or refractory Hodgkin's Lymphoma. ^{1 4 6 10 11}

Research Team

David McCall, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with relapsed/refractory Hodgkin's Lymphoma who are not candidates for high-dose chemotherapy. Participants must have certain levels of liver function, agree to contraception if applicable, and can't be pregnant or breastfeeding. Prior treatments with checkpoint inhibitors are allowed, but no recent immunosuppressants or live vaccines.

Inclusion Criteria

Total bilirubin < 2 x upper limit of normal (ULN) unless increase is due to Gilbert's disease

I am at least 1 year old and can be treated at the pediatric/adolescent center.

My Hodgkin lymphoma has returned or worsened, but I've had checkpoint inhibitors before.

Exclusion Criteria

I do not have any severe ongoing health issues like uncontrolled infections, heart problems, or high blood pressure.

I have not received a live vaccine in the last 30 days.

I do not have HIV or active hepatitis B or C.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pembrolizumab every 3 weeks and Azacitidine on Days 1-7 of each 28-day cycle

28-day cycles

Pembrolizumab every 3 weeks, Azacitidine Days 1-7

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Azacytidine (Anti-metabolites)
• Pembrolizumab (Monoclonal Antibodies)

Trial Overview The study tests the combination of Azacitidine and Pembrolizumab in treating Hodgkin's Lymphoma that has returned or resisted other treatments. It aims to evaluate how effective and safe this drug duo is when given together over a 7-day regimen.

Participant Groups

Group I: Pembrolizumab plus Azacitidine Experimental Treatment 2 Interventions

Pembrolizumab by vein over about 30 minutes every 3 weeks. Azacitidine by vein over about 60-90 minutes on Days 1-7 of each 28-day study cycle

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

Findings from Research

In a phase 2 trial involving 30 patients with untreated advanced-stage classic Hodgkin lymphoma, nearly two-thirds achieved complete or near-complete metabolic responses after receiving pembrolizumab alone, and all patients achieved complete responses after subsequent AVD chemotherapy, with a 100% overall survival rate at a median follow-up of 33.1 months.

The study found that all patients had genomic alterations in chromosome 9p24.1 and were positive for PD-L1, indicating that even low levels of PD-L1 expression can lead to effective responses to PD-1 blockade, suggesting a broad applicability of this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma. Allen, PB., Lu, X., Chen, Q., et al.[2023]

The combination of pembrolizumab and vorinostat was found to be tolerable in patients with relapsed/refractory B-cell lymphomas, although there were serious adverse events, including one case of Stevens-Johnson syndrome that led to a fatal infection.

The treatment showed promising efficacy, especially in primary mediastinal B-cell lymphoma (PMBL), with a complete response rate of 80% and overall response rate of 80%, while overall response rates for other non-PMBL diffuse large B-cell lymphoma (DLBCL) were lower at 33%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin lymphoma. Godfrey, J., Mei, M., Chen, L., et al.[2023]

In a phase II study involving 210 patients with relapsed or refractory classic Hodgkin lymphoma, pembrolizumab showed a high overall response rate of 69%, indicating its effectiveness as a treatment option.

The safety profile of pembrolizumab was consistent with previous studies, suggesting it is a well-tolerated therapy for patients with this challenging form of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. Chen, R., Zinzani, PL., Fanale, MA., et al.[2022]

In the KEYNOTE-087 study, pembrolizumab demonstrated a 69% overall response rate in patients with relapsed/refractory classical Hodgkin lymphoma, indicating its efficacy as a treatment option.

Health-related quality of life assessments showed significant improvements in overall health and functional scores among 206 patients at 12 and 24 weeks, suggesting that pembrolizumab not only helps in treating the disease but also enhances patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in KEYNOTE-087, a phase 2 study of pembrolizumab in patients with classical Hodgkin lymphoma. von Tresckow, B., Fanale, M., Ardeshna, KM., et al.[2020]

In a study of 30 patients with untreated classic Hodgkin lymphoma, the combination of pembrolizumab with chemotherapy (AVD) demonstrated a 100% overall response rate and a 90% complete response rate, indicating high efficacy.

The treatment was generally safe, with no significant delays in administration; however, some patients experienced serious adverse events, including febrile neutropenia and immune-related effects, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma. Lynch, RC., Ujjani, CS., Poh, C., et al.[2023]

In a phase Ib study involving 31 patients with relapsed or refractory Hodgkin lymphoma, pembrolizumab showed a favorable safety profile with only 16% experiencing grade 3 drug-related adverse events and no grade 4 adverse events or treatment-related deaths.

The treatment resulted in a 16% complete remission rate and a 65% overall response rate, with most responses lasting over 24 weeks, indicating that pembrolizumab may be an effective option for patients who have undergone multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. Armand, P., Shipp, MA., Ribrag, V., et al.[2022]

In a small study of 10 patients with relapsed or refractory classical Hodgkin lymphoma, 78% achieved a complete response after treatment with immune checkpoint inhibitors (pembrolizumab or nivolumab), indicating a promising efficacy in this difficult-to-treat population.

Patients who had previously received 5-azacitidine showed a higher complete response rate (100%) compared to those who had not (50%), suggesting that hypomethylating agents may enhance the effectiveness of immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High rate of complete responses to immune checkpoint inhibitors in patients with relapsed or refractory Hodgkin lymphoma previously exposed to epigenetic therapy. Falchi, L., Sawas, A., Deng, C., et al.[2018]

In a phase 2 trial involving 30 patients with newly diagnosed classical Hodgkin lymphoma, pembrolizumab monotherapy led to a complete metabolic response (CMR) in 37% of patients, demonstrating its efficacy as an initial treatment.

The combination of pembrolizumab followed by AVD chemotherapy was well tolerated, with no disease progression or deaths reported during a median follow-up of 22.5 months, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma. Allen, PB., Savas, H., Evens, AM., et al.[2022]

References

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

Sequential pembrolizumab and AVD are highly effective at any PD-L1 expression level in untreated Hodgkin lymphoma. [2023]

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

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]

3. Italy pubmed.ncbi.nlm.nih.gov

Results from a phase I trial of pembrolizumab plus vorinostat in relapsed/refractory B-cell non-Hodgkin lymphoma. [2023]

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

Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. [2022]

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

Patient-reported outcomes in KEYNOTE-087, a phase 2 study of pembrolizumab in patients with classical Hodgkin lymphoma. [2020]

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

Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma. [2023]

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

Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. [2022]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]

10. England pubmed.ncbi.nlm.nih.gov

High rate of complete responses to immune checkpoint inhibitors in patients with relapsed or refractory Hodgkin lymphoma previously exposed to epigenetic therapy. [2018]

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

Pembrolizumab followed by AVD in untreated early unfavorable and advanced-stage classical Hodgkin lymphoma. [2022]