Azacitidine + Pembrolizumab for Hodgkin's Lymphoma

Overseen By David McCall, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Live vaccines

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

Compensation: Varies

Number of Visits: 3

Duration: 28-day cycles

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two medications, azacitidine (a chemotherapy drug) and pembrolizumab (an immunotherapy drug), to treat Hodgkin's lymphoma that has returned or isn't responding to other treatments. The research examines the effectiveness, safety, and impact on patients' daily lives. Suitable candidates for this trial include those with Hodgkin's lymphoma that has relapsed or involves areas outside the lymph nodes and who cannot undergo high-dose chemotherapy. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from a potentially effective new therapy.

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.

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

Research shows that using azacitidine and pembrolizumab together is generally safe. Previous studies found that most people tolerate this combination well. The side effects typically resemble those of other cancer treatments and include tiredness, nausea, and low blood cell counts. Although these side effects can be uncomfortable, they are usually not severe. These treatments have been used for other conditions, providing some confidence in their safety. Always consult your doctor if you have any concerns. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for Hodgkin's Lymphoma?

Researchers are excited about the combination of Azacitidine and Pembrolizumab for treating Hodgkin's Lymphoma because it represents a novel approach to tackling the disease. Most current treatments, like chemotherapy and radiation, focus on destroying cancer cells directly. However, Pembrolizumab is an immunotherapy that works by blocking a protein (PD-1) on immune cells, thereby unleashing the immune system to attack cancer cells more effectively. Azacitidine, on the other hand, is a hypomethylating agent that can modify the cancer cell environment, potentially making them more susceptible to immune attacks. This combination could enhance the body's natural ability to fight cancer, offering a new hope for patients who might not respond well to conventional therapies.

What evidence suggests that this treatment might be an effective treatment for Hodgkin's Lymphoma?

Research has shown that using azacitidine with pembrolizumab might help treat Hodgkin's Lymphoma, particularly if it has returned or hasn't responded to other treatments. In this trial, participants will receive a combination of pembrolizumab, which aids the immune system in recognizing cancer cells, and azacitidine. Studies indicate that adding pembrolizumab to azacitidine can enhance the body's ability to combat cancer. Early trial results suggest this combination might reduce tumor size in some patients. This treatment activates T-cells, a part of the immune system, to better target and destroy cancer cells. ^{1 2 3 4 6}

Who Is on the Research Team?

David McCall, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 am allergic to azacitidine, pembrolizumab, or their ingredients.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Azacytidine
• Pembrolizumab

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.

How Is the Trial Designed?

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

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

Approved in United States as Vidaza for:

• Myelodysplastic Syndrome
• Acute Myeloid Leukemia
• Juvenile Myelomonocytic Leukemia

Approved in European Union as Vidaza for:

• Myelodysplastic Syndrome
• Acute Myeloid Leukemia
• Juvenile Myelomonocytic Leukemia

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

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 trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

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]

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]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

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]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

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. Abdel-Rahman, O.[2018]

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 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 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 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]

Citations

1. withpower.com withpower.com/trial/phase-2-lymphoma-9-2022-ad689

Azacitidine + Pembrolizumab for Hodgkin's Lymphoma Trial Overview The study tests the combination of Azacitidine and Pembrolizumab in treating Hodgkin's Lymphoma that has returned or resisted other treatments.

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/736/531082/Efficacy-and-Safety-of-Pembrolizumab-Added-to

Efficacy and Safety of Pembrolizumab Added to Azacitidine ... Addition of anti-PD-1 antibody to AZA+VEN may activate T-cells against blasts, induce higher rates of measurable residual disease (MRD)- ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-03778

Azacitidine and Pembrolizumab for the Treatment of ... This phase II trial studies how well azacitidine and pembrolizumab work to shrink tumors in patients with Hodgkin lymphoma and acute myeloid leukemia that ...

4. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2021-0916.html

A phase II study of the combination of Azacitidine and ... 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 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124034839

Efficacy and Safety of Pembrolizumab Added to Azacitidine ... Addition of anti-PD-1 antibody to AZA+VEN may activate T-cells against blasts, induce higher rates of measurable residual disease (MRD)-negativity (neg), and ...

6. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05355051/

Trial | NCT05355051 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 ...