Pembrolizumab + Chemotherapy for Hodgkin's Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS involvement, Active infection, Autoimmune disease, 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

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

Compensation: Varies

Number of Visits: 28

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of pembrolizumab (a type of immunotherapy) and chemotherapy to determine its effectiveness for patients with Hodgkin's lymphoma who cannot tolerate standard treatments. The goal is to find a safe and effective alternative by using drugs that help the immune system fight cancer and target and kill cancer cells. This trial suits individuals newly diagnosed with classical Hodgkin lymphoma who have limitations, such as heart or lung issues, that make standard chemotherapy risky. It is not suitable for those who have received previous treatment for Hodgkin lymphoma or have active infections or certain other medical conditions. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a promising alternative for those seeking new options.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain investigational therapies or live vaccines close to the start of the trial, and there are restrictions on using corticosteroids and other immunosuppressive medications. It's best to discuss your specific medications with the study team.

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

Research has shown that the combination of pembrolizumab and gemcitabine is generally safe for patients with Hodgkin lymphoma. In one study, nearly all patients (95%) achieved a complete response after just two treatment cycles, indicating both safety and effectiveness. Most patients tolerated the treatment well, with very few discontinuing due to side effects.

Similarly, the combination of pembrolizumab with brentuximab vedotin and dacarbazine has demonstrated promising safety results. Studies have found this combination effective without causing major treatment delays or severe side effects. For patients with Hodgkin lymphoma, these treatments have proven to be safe options, instilling confidence in their use.

These findings suggest that the treatments tested in this trial have a strong safety record, which may reassure those considering participation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Hodgkin’s Lymphoma because they combine pembrolizumab, a checkpoint inhibitor, with chemotherapy agents like Brentuximab Vedotin, Dacarbazine, and Gemcitabine. Pembrolizumab works by enhancing the immune system's ability to detect and attack cancer cells, which is different from standard chemotherapy that directly targets and destroys cancer cells. This combination aims to provide a more comprehensive approach by both boosting the immune response and attacking the cancer directly. This dual approach could potentially improve treatment effectiveness and outcomes for patients.

What evidence suggests that pembrolizumab plus chemotherapy could be an effective treatment for Hodgkin's lymphoma?

This trial will evaluate the effectiveness of combining pembrolizumab with either gemcitabine or with brentuximab vedotin and dacarbazine for treating Hodgkin's lymphoma. Research has shown that using pembrolizumab with gemcitabine is highly effective. Specifically, earlier studies indicated that 95% of patients had their cancer completely disappear after just two rounds of treatment. Another study found that all patients experienced some reduction in their cancer. When pembrolizumab was combined with brentuximab vedotin and dacarbazine, about 95% of patients responded positively, with 81% achieving complete remission. These treatments help the immune system find and destroy cancer cells, offering hope for those who can't undergo standard treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Matthew Mei

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for frail patients with newly diagnosed Hodgkin lymphoma who are not suitable for standard anthracycline-based treatments. Participants should be able to undergo various tests like CT scans, echocardiography, PET scans, and pulmonary function tests.

Inclusion Criteria

Documented informed consent of the participant and/or legally authorized representative

Assent, when appropriate, will be obtained per institutional guidelines

Agreement to allow the use of archival tissue from diagnostic tumor biopsies

Exclusion Criteria

I have or might have had HLH in the past.

I haven't had a stroke, heart attack, or severe heart symptoms in the last 6 months.

Any other condition that would contraindicate the patient's participation in the clinical study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pembrolizumab and gemcitabine intravenously every 21 days for up to 8 cycles

24 weeks

8 visits (in-person)

Maintenance Therapy

Participants receive pembrolizumab intravenously every 42 days for up to 4 cycles

24 weeks

4 visits (in-person)

Salvage Therapy

Participants receive pembrolizumab, brentuximab vedotin, and dacarbazine intravenously every 21 days for up to 12 cycles

36 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Brentuximab Vedotin
• Dacarbazine
• Gemcitabine
• Pembrolizumab

Trial Overview The study is testing the effectiveness of pembrolizumab combined with chemotherapy drugs gemcitabine, brentuximab vedotin, and dacarbazine in treating Hodgkin lymphoma. It's a phase II trial aiming to see if this combination can help the immune system fight cancer better.

How Is the Trial Designed?

Group I: Treatment (P-G, P-BV-D) Experimental Treatment 10 Interventions

See Detailed Description.

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8869808/

Brentuximab Vedotin and Pembrolizumab Combination in ... In this retrospective study, we evaluated the efficacy of a combination of brentuximab vedotin (BV) and pembrolizumab in a series of HL patients ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05922904

PET Adapted Brentuximab Vedotin and Pembrolizumab in ... To learn about the effects of brentuximab vedotin and pembrolizumab in combination with doxorubicin and dacarbazine when given to patients who have Stage II ...

3. nature.com nature.com/articles/s41408-025-01257-1

Outcomes in patients with classic Hodgkin lymphoma ... Anti-PD-1 based therapies and brentuximab vedotin (BV) have significantly improved survival in patients with classic Hodgkin lymphoma (cHL)

4. mdpi.com mdpi.com/2227-9059/13/2/252

Combination of Brentuximab Vedotin and Pembrolizumab ... Results: After two cycles of brentuximab vedotin and pembrolizumab, 95.2% achieved an overall response and 81.0% achieved complete metabolic response. 20 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123006675

Concurrent pembrolizumab with AVD for untreated classic ... With a median follow-up of 2.1 years, the 2-year progression-free survival (PFS) and overall survival were 97% and 100%, respectively. To date, ...

6. ashpublications.org ashpublications.org/blood/article/141/21/2576/494889/Concurrent-pembrolizumab-with-AVD-for-untreated

Concurrent pembrolizumab with AVD for untreated classic ... Concurrent APVD was safe and effective in untreated HL without clinically significant treatment delays. CR rates by PET were lower ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025022037

HL-850: Clinical Efficacy and Safety of Pembrolizumab and ... HL-850: Clinical Efficacy and Safety of Pembrolizumab and Nivolumab in Frontline Treatment for Classical Hodgkin Lymphoma: A Systematic Review and Meta-Analysis.

8. asco.org asco.org/abstracts-presentations/ABSTRACT210989

Improving outcomes with brentuximab vedotin (BV) plus ... Improving outcomes with brentuximab vedotin (BV) plus chemotherapy in patients with newly diagnosed advanced stage Hodgkin lymphoma. ; 95% CI, 0.31, 1.07, 0.62, ...