Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing the combination of pembrolizumab and GVD chemotherapy in patients with Hodgkin lymphoma. Pembrolizumab boosts the immune system to fight cancer, and GVD directly kills cancer cells. Pembrolizumab has shown effectiveness in treating classical Hodgkin lymphoma, especially in patients who have relapsed after initial treatments.
Is the drug combination of Gemcitabine, Pembrolizumab, and Vinorelbine promising for treating Hodgkin's Lymphoma?Yes, the combination of Gemcitabine, Pembrolizumab, and Vinorelbine shows promise for treating Hodgkin's Lymphoma. Pembrolizumab, in particular, has demonstrated high response rates in patients with relapsed or difficult-to-treat Hodgkin's Lymphoma, offering a new approach to treatment.56789
What safety data is available for the treatment of Pembrolizumab + GVD in Hodgkin's Lymphoma?The safety data for the treatment of Pembrolizumab combined with Gemcitabine and Vinorelbine (GVD) in Hodgkin's Lymphoma can be inferred from several studies. A phase II study evaluated Pembrolizumab plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as a second-line therapy for relapsed or refractory classical Hodgkin lymphoma, indicating its use in this context. Additionally, a study on Gemcitabine and Vinorelbine in pediatric patients with relapsed/refractory Hodgkin's disease assessed the efficacy and toxicity of these agents, providing insights into their safety profile. While these studies provide some safety data, specific results on adverse effects or toxicity levels would be detailed in the full study reports.23468
What data supports the idea that Pembrolizumab + GVD for Hodgkin's Lymphoma is an effective treatment?The available research shows that Pembrolizumab combined with Gemcitabine, Vinorelbine, and liposomal Doxorubicin (pembro-GVD) is effective as a second-line treatment for patients with relapsed or refractory classical Hodgkin's Lymphoma. This combination was specifically studied in a phase II trial, which suggests it can be beneficial for patients who have not responded to initial treatments. Additionally, Pembrolizumab alone has been compared to standard treatments for similar patients and is considered a promising option. While other studies focus on Gemcitabine and Vinorelbine for different conditions or in different combinations, the specific combination with Pembrolizumab shows promise for Hodgkin's Lymphoma based on the trial results.12468
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, if you have an active autoimmune disease that required systemic treatment in the past 2 years, or if you have an active infection requiring systemic therapy, you may not be eligible. It's best to discuss your current medications with the trial team.
Eligibility Criteria
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 fully active or restricted in physically strenuous activity but can do light work.
I am 18 years old or older.
My cancer returned or didn't respond after one chemotherapy treatment.
My cancer came back or didn't respond to treatment, confirmed by a biopsy.
I have been diagnosed with classical Hodgkin's lymphoma.
Exclusion Criteria
I have had more than one treatment for Hodgkin Lymphoma.
I have not received a live vaccine within the last 30 days.
I do not have active HIV, Hepatitis B, or Hepatitis C.
I haven't needed systemic treatment for an autoimmune disease in the last 2 years.
I am currently being treated for an infection.
I have had pneumonitis treated with steroids or have it now.
I have cancer that has spread to my brain or spinal cord.
Treatment Details
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.
6Treatment groups
Experimental Treatment
Group I: Safety monitoring beyond after completion of safety window (PART 1)Experimental Treatment5 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 Treatment5 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 Treatment5 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 Treatment5 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 Treatment5 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 Treatment5 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Memoral Sloan Kettering MonmouthMiddletown, NJ
Memoral Sloan Kettering Basking RidgeBasking Ridge, NJ
Memoral Sloan Kettering WestchesterHarrison, NY
University of MiamiMiami, FL
More Trial Locations
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Who is running the clinical trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
Merck Sharp & Dohme LLCIndustry Sponsor
References
Gemcitabine and vinorelbine as a salvage regimen for relapse in Hodgkin lymphoma after autologous hematopoietic stem cell transplantation. [2022]The authors describe two consecutive pediatric patients with relapsed Hodgkin lymphoma after autologous hematopoietic stem cell transplantation who had objective responses with a novel combination of gemcitabine and vinorelbine. This novel and promising combination needs to be studied in a larger number of relapsed Hodgkin disease patients.
Phase II study of weekly gemcitabine and vinorelbine for children with recurrent or refractory Hodgkin's disease: a children's oncology group report. [2022]The Children's Oncology Group conducted this phase II study to assess the efficacy and toxicity of gemcitabine and vinorelbine (GV) in pediatric patients with heavily pretreated relapsed/refractory Hodgkin's disease. Both agents have significant single-agent response rates in this setting.
A phase II study of gemcitabine combined with vinorelbine as first-line chemotherapy for metastatic breast cancer. [2022]There is an unmet need for new combination treatments, especially for aggressive, visceral, and high tumor burden metastatic breast cancer. Gemcitabine (GEM) has shown synergy with vinorelbine (VRL) in preclinical models, and has a toxicity profile that is different from VRL, another recently approved cytotoxic drug that seems to be effective in the treatment of breast cancer.
Biweekly vinorelbine and gemcitabine as second-line treatment and beyond in non-small cell lung cancer. [2022]To evaluate the activity and tolerance of gemcitabine (GEM) in combination with vinorelbine (VRL) in pretreated patients with advanced non-small cell lung cancer (NSCLC).
Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. [2022]Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response ≥ 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.
Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin's lymphoma progressing after brentuximab vedotin: an indirect treatment comparison. [2019]There is significant unmet need among patients with relapsed and refractory classical Hodgkin's lymphoma (RRcHL) who have failed multiple lines of therapy, including brentuximab vedotin (BV). Pembrolizumab, an immune checkpoint inhibitor, is one possible treatment solution for this population.
Prolonged Remission by Pembrolizumab and Brentuximab-Vedotin Combination Therapy in Heavily-Pretreated Relapsed/Refractory Hodgkin's Lymphoma. [2020]Hodgkin's lymphoma (HL) is usually sensitive and curative to multi-agent chemotherapy, but may become refractory disease in a subset of relapsed patients. Recent novel agents, brentuximab-vedotin (BV) and immune checkpoint inhibitors have significantly improve the treatment outcome. We report the outcome by combination of BV with pembrolizumab in a patient with a relapsed/refractory HL in a remarkable and durable response, even previously failed to multiple lines of chemotherapy, or brentuximab-vedotin/pembrolizumab monotherapy. Further investigation of immunotherapy combination in relapsed/refractory HL is needed.
Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma. [2023]We conducted a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) as second-line therapy for relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) (ClinicalTrials.gov identifier: NCT03618550).
Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma. [2023]Concurrent administration of pembrolizumab with chemotherapy in untreated classic Hodgkin lymphoma (CHL) has not been studied previously. To investigate this combination, we conducted a single-arm study of concurrent pembrolizumab with AVD (doxorubicin, vinblastine, and dacarbazine; APVD) for untreated CHL. We enrolled 30 patients and met the primary safety end point with no observed significant treatment delays in the first 2 cycles. Twelve patients experienced grade 3 or 4 nonhematologic adverse events (AEs), most commonly febrile neutropenia and infection/sepsis. Grade 3 or 4 immune-related AEs, including alanine aminotransferase elevation and aspartate aminotransferase elevation were observed in 3 patients. One patient experienced an episode of grade 2 colitis and arthritis. Six patients missed at least 1 dose of pembrolizumab because of AEs, primarily grade 2 or higher transaminitis. Among 29 response-evaluable patients, the best overall response rate was 100% and the complete response rate was 90%. 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, no patient who has withheld or discontinued pembrolizumab because of toxicity has progressed. Clearance of circulating tumor DNA (ctDNA) was associated with superior PFS when measured after cycle 2 and at the end of treatment (EOT). None of the 4 patients with persistent uptake by fluorodeoxyglucose positron emission tomography (PET) at EOT yet negative ctDNA have relapsed to date. Concurrent APVD shows promising safety and efficacy but may yield spurious PET findings in some patients. This trial was registered at www.clinicaltrials.gov as #NCT03331341.