Pembrolizumab + GVD for Hodgkin's Lymphoma

Recruiting at 11 trial locations

Overseen By Heiko Schoder, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Pregnancy, CNS metastases, Active infection, 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: Unknown

257 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effects of a new treatment combination for Hodgkin's lymphoma, using pembrolizumab (an immunotherapy drug) with other drugs like gemcitabine and vinorelbine. Researchers aim to determine the effectiveness of this combination and identify any side effects. The study is open to individuals with Hodgkin's lymphoma who have not responded to previous chemotherapy or have experienced a relapse. Participants must have undergone at least one unsuccessful treatment before joining. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on medications for active autoimmune diseases or have received certain vaccines recently, you may need to discuss this with the trial team.

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

Research has shown that pembrolizumab, one of the drugs in this trial, is generally safe but can cause some side effects. In earlier studies, about 5% of patients stopped using pembrolizumab due to side effects, and around 26% paused treatment because of them. Common side effects include fatigue and nausea.

Gemcitabine, another drug in the trial, has been studied in patients with relapsed lymphoma. It is considered safe and effective and is often used in outpatient settings. Most side effects can be managed, with the main concern being non-blood-related side effects.

Vinorelbine, the third drug in the trial, is also safe and well-tolerated. The main side effect is a low count of certain white blood cells, which can increase infection risk.

These treatments have been studied alongside chemotherapy for different types of cancer, including Hodgkin's lymphoma. Each drug has its own safety profile, but overall, they are used effectively in cancer treatment. Participants should be aware of possible side effects and discuss any concerns with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab with GVD (gemcitabine, vinorelbine, and doxorubicin) for Hodgkin's Lymphoma because it introduces an innovative approach to treatment. Pembrolizumab is an immune checkpoint inhibitor that enhances the body's immune response against cancer cells, which is different from the traditional chemotherapy regimens like ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or BEACOPP. This combination specifically targets the PD-1 pathway, potentially offering a more robust immune response and longer-lasting effects. Additionally, the integration of autologous stem cell transplant (ASCT) and involved-site radiation therapy (ISRT) could further optimize outcomes by consolidating treatment gains and targeting residual disease.

What evidence suggests that this trial's treatments could be effective for Hodgkin's Lymphoma?

Research has shown that using pembrolizumab with GVD (a mix of gemcitabine, vinorelbine, and doxorubicin) effectively treats Hodgkin's lymphoma. In this trial, participants will receive pembrolizumab combined with GVD, especially when the initial treatment fails. This combination has enabled patients to proceed to stem cell transplants, a crucial step for those whose lymphoma has returned or hasn't responded to other treatments. Additionally, some participants will receive pembrolizumab alone as maintenance therapy. Previous studies have demonstrated positive outcomes with this approach, with many patients responding well and experiencing longer survival. These findings suggest that pembrolizumab, both alone and with GVD, offers promising results for individuals with this type of lymphoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Alison Moskowitz, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with classical Hodgkin's lymphoma that has returned or didn't respond after one multi-agent chemotherapy can join. They must have good heart function, no pregnancy, adequate organ function, and agree to use contraception. Excluded are those with more than one prior treatment, active CNS metastases, certain medical conditions or infections, recent live vaccines, a history of pneumonitis requiring steroids, or an organ transplant.

Inclusion Criteria

I am willing to use birth control during the study.

I am fully active or restricted in physically strenuous activity but can do light work.

My organs are functioning well.

Exclusion Criteria

I do not have active HIV, Hepatitis B, or Hepatitis C.

Known pregnancy or breast-feeding

I have had more than one treatment for Hodgkin Lymphoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Window and DLT definition (Part 1)

Initially, 6 patients will be treated on the safety portion of the study and observed for dose limiting toxicities (DLTs).

4-6 weeks

Treatment (Part 2)

Patients receive pembrolizumab-GVD for 4 cycles, followed by single-agent pembrolizumab for 13 cycles.

16-18 months

Autologous Stem Cell Transplant (ASCT) (Parts 1 and 3)

Stem cell mobilization and collection performed after 2-4 cycles of pembrolizumab-GVD.

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including 100 days following the last dose of pembrolizumab.

3-4 months

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Pembrolizumab
• Vinorelbine

Trial Overview The trial is testing the effectiveness and safety of pembrolizumab combined with GVD (gemcitabine, vinorelbine, liposomal doxorubicin) as a second-line treatment for relapsed or refractory Hodgkin lymphoma. Participants will receive this combination therapy to see how well it works compared to previous treatments.

How Is the Trial Designed?

Group I: Safety monitoring beyond after completion of safety window (PART 1) Experimental Treatment 5 Interventions

During the phase II portion of the study, patients will continue to be monitored for DLTs, adverse events, and events of interest throughout treatment with pembrolizumab-GVD, ASCT (part 1, if applicable), and 100 days following the last dose of pembrolizumab. Total planned enrollment is 39 patients

Group II: Safety Window and DLT definition (Part 1) Experimental Treatment 5 Interventions

Initially, 6 patients will be treated on the safety portion of the study and observed for dose limiting toxicities (DLTs). If 1 or fewer patients experience dose\[1\]limiting toxicity (DLT), enrollment onto the study will proceed according to a phase II, Simon 2- stage design.

Group III: Pembrolizumab maintenance, third-line therapy, and HDT/ASCT (PART 3) Experimental Treatment 5 Interventions

In part 3 of the study, patients who achieve complete response after 2 cycles of pembrolizumab\[1\]GVD will be randomized to either consolidation with autologous stem cell transplant (after an additional optional 1-2 cycles of pembro-GVD) or 2 cycles of pembro-GVD followed by single agent pembrolizumab maintenance for 13 cycles.

Group IV: Pembrolizumab maintenance (PART 2) Experimental Treatment 5 Interventions

In part 2 of the study, patients who achieve complete response after 4 cycles of pembrolizumab\[1\]GVD will receive single-agent pembrolizumab for 13 cycles, which will begin 3-5 weeks after cycle 4 of pembrolizumab-GVD.

Group V: Involved-site radiation therapy (ISRT) (PART 3) Experimental Treatment 5 Interventions

Patients with limited sites of disease prior to initiation of pembro-GVD are eligible to receive ISRT prior to ASCT with pembrolizumab maintenance.

Group VI: Autologous Stem Cell Transplant (ASCT) (PARTS 1 and 3) Experimental Treatment 5 Interventions

Stem cell mobilization and collection will be performed as per institutional guidelines after 2-4 cycles of pembrolizumab-GVD.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

A patient with relapsed/refractory Hodgkin's lymphoma showed a remarkable and durable response to the combination of brentuximab-vedotin and pembrolizumab, even after failing multiple previous treatments.

This case highlights the potential of combining novel agents like BV and immune checkpoint inhibitors to improve treatment outcomes in difficult-to-treat Hodgkin's lymphoma, suggesting further research is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged Remission by Pembrolizumab and Brentuximab-Vedotin Combination Therapy in Heavily-Pretreated Relapsed/Refractory Hodgkin's Lymphoma. Yu, TY., Dai, MS.[2020]

In a phase II study involving 30 pediatric patients with relapsed or refractory Hodgkin's disease, the combination of gemcitabine and vinorelbine (GV) showed a high response rate, with 76% of assessable patients achieving measurable responses, including complete and very good partial responses.

GV was found to be well-tolerated, with predominant hematologic toxicity but no toxic deaths, indicating it is a safe reinduction treatment option for heavily pretreated children with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of weekly gemcitabine and vinorelbine for children with recurrent or refractory Hodgkin's disease: a children's oncology group report. Cole, PD., Schwartz, CL., Drachtman, RA., et al.[2022]

In a phase II study involving 74 patients with metastatic breast cancer, the combination of gemcitabine (GEM) and vinorelbine (VRL) showed promising efficacy, achieving an overall response rate of 42% with 6% complete responses and 36% partial responses.

The treatment demonstrated good tolerability, with manageable side effects; however, 10% of patients experienced severe neutropenia, and common toxicities included nausea (24%) and febrile neutropenia (11%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of gemcitabine combined with vinorelbine as first-line chemotherapy for metastatic breast cancer. Shehata, S., Saad, E., Goda, Y., 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 II study of 39 patients with relapsed or refractory classical Hodgkin lymphoma, the combination of pembrolizumab with gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) resulted in a remarkable overall response rate of 100% and a complete response rate of 95%.

The treatment was well-tolerated, with most adverse events being mild (grade 1 or 2), and 95% of patients successfully proceeded to high-dose therapy and autologous hematopoietic cell transplantation, with all transplanted patients remaining in remission at a median follow-up of 13.5 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma. Moskowitz, AJ., Shah, G., Schöder, H., et al.[2023]

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]

Two pediatric patients with relapsed Hodgkin lymphoma showed positive responses to a new treatment combining gemcitabine and vinorelbine after failing previous therapies, including autologous stem cell transplantation.

This promising combination treatment warrants further investigation in larger clinical trials to assess its efficacy and safety in a broader population of relapsed Hodgkin lymphoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and vinorelbine as a salvage regimen for relapse in Hodgkin lymphoma after autologous hematopoietic stem cell transplantation. Ozkaynak, MF., Jayabose, S.[2022]

In a trial involving 15 patients with advanced non-small cell lung cancer (NSCLC), the combination of gemcitabine and vinorelbine showed no complete or partial responses, with only 27% of patients experiencing stable disease.

The treatment was found to be safe, with infrequent severe myelotoxicity, but ultimately ineffective, leading to the conclusion that this regimen is not recommended as a second-line treatment for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly vinorelbine and gemcitabine as second-line treatment and beyond in non-small cell lung cancer. Chelis, L., Xenidis, N., Amarantidis, K., et al.[2022]

In patients with relapsed and refractory classical Hodgkin's lymphoma who have previously failed treatment with brentuximab vedotin, pembrolizumab significantly improves progression-free survival (PFS) compared to standard of care, with hazard ratios indicating a much lower risk of disease progression.

The study involved a systematic literature review and comparisons of outcomes from pembrolizumab's KEYNOTE-087 trial against an observational study of standard care, confirming that pembrolizumab is a more effective treatment option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison. Keeping, S., Wu, E., Chan, K., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10602819/

Effectiveness and Safety of Pembrolizumab in Recurrent and ... Pembrolizumab is consistently described as being extremely efficacious in treating cHL in many researches, including those by Armand et al., ...

2. ashpublications.org ashpublications.org/blood/article/142/10/878/496370/Five-year-follow-up-of-KEYNOTE-087-pembrolizumab

Five-year follow-up of KEYNOTE-087: pembrolizumab ... The median OS was not reached (95% CI, 26.8-NR), and the 5-year OS rate was 53.7% (Figure 3C). Among the 33 patients with disease progression, ...

3. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05008224

NCT05008224 | Study of Safety and Efficacy ... The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) monotherapy, followed by chemotherapy, followed by pembrolizumab ...

4. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

5. aol.amegroups.org aol.amegroups.org/article/view/6756/html

Effectiveness and safety of pembrolizumab as bridging to ... The response was assessable in 29 patients, 78% of the patients responded to pembrolizumab, 17 (53%) underwent hematopoietic stem cell ...

6. bccancer.bc.ca bccancer.bc.ca/drug-database-site/Drug%20Index/Gemcitabine_monograph.pdf

DRUG NAME: Gemcitabine Gemcitabine, a pyrimidine analog, is structurally similar to cytarabine, but has a wider spectrum of antitumour activity.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3018339/

Efficacy and Safety of Gemcitabine (G), Carboplatin (C ... GCD(R) is a safe and effective outpatient regimen for relapsed lymphoma and successfully mobilizes PBSC.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00388349

Gemcitabine and Hodgkin's Disease Chemotherapy ... To assess the non-hematologic toxicity and determine the phase 2 dose of gemcitabine in combination with vinorelbine followed by carmustine, etoposide and ...

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)55065-7/pdf

Gemcitabine for relapsed or resistant lymphoma We have examined the efficacy and safety of gemcitabine in patients with relapsed or resistant lymphoma. Patients and methods: Gemcitabine (1 g/m2) was given.

10. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S1526-9655(11)70256-1/fulltext

Gemcitabine and Its Combinations in the Treatment of ... Although combination chemotherapy can induce complete remission in a large proportion of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma ...