Hodgkin LymphomaPhase 2NCT03618550
Phase II Study of Second- Line Pembrolizumab Plus GVD for Relapsed or Refractory Hodgkin Lymphoma
A Phase 2 study testing pembrolizumab, gemcitabine and vinorelbine in people with Hodgkin Lymphoma and Relapsed or Refractory Hodgkin Lymphoma, run by Memorial Sloan Kettering Cancer Center at 10 sites in United States.
Trial summary
The purpose of this study is to test any good and bad effects of the study drug, pembrolizumab, in combination with GVD in the treatment of Hodgkin lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hodgkin Lymphoma, Relapsed or Refractory Hodgkin Lymphoma
- What is being tested?
- pembrolizumab, gemcitabine and vinorelbine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 257 participants
- Where
- 10 sitesUnited States
- Study dates
- 1 Aug 2018to Aug 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic diagnosis of classical Hodgkin's lymphoma. Primary refractory or relapsed disease proven by biopsy at enrolling institution.
- Be willing and able to provide written informed consent/assent for the trial.
- Be ≥ 18 years of age on day of signing informed consent.
- PET scan before initiating pembro-GVD have measurable disease based on Lugano 2014 criteria
- Have a performance status of 0 or 1 on the ECOG Performance Scale
- Demonstrate adequate organ function as defined in table below
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- Demonstrate adequate organ function as defined in table below. Hematological*
- Absolute neutrophil count (ANC) ≥1000 /mcL
- Platelets ≥50,000 / mcL
- Hemoglobin ≥8 g/dL Renal
- Serum creatinine OR ≤1.5 X upper limit of normal (ULN) OR
- Measured or calculated creatinine clearance (eGFR can also be used in place of creatinine) ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN Hepatic*
- Serum total bilirubin ≤ 1.5 X ULN OR ≤ 3 X ULN for subjects with liver metastases
- AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases Pulmonary
- Hemoglobin-adjusted diffusing capacity for carbon monoxide ≥50% (If unadjusted DLCO is >/= 50% then there is no need to calculate adjusted) Cardiac
- Ejection fraction ≥45% Coagulation
- International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT): ≤ 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
- Lab values for eligibility should be based upon labs prior to Cycle 1 treatment of Pembro-GVD.
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 2 weeks prior to receiving the first dose of study medication. On the day of planned treatment, if a blood pregnancy test has not been performed within the two week window, a stat pregnancy test (urine or blood) should be performed and the results reviewed before treatment is begun.
- Female subjects of childbearing potential must be willing to use an adequate method of contraception (see details in section 11.4.3).
- Male subjects of childbearing potential must agree to use an adequate method of contraception.(see details in section 11.4.3).
- HIV-infected participants must have well-controlled HIV on ART, defined as:
- Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening
- Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening
- It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months.
- Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study
- Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible.
Who cannot join
- Known pregnancy or breast-feeding.
- Breast-feeding should be discontinued prior to treatment initiation.
- Medical illness unrelated to Hodgkin's Lymphoma, which, in the opinion of the attending physician and/or principal investigator, makes participation in this study inappropriate.
- Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
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- Has known active HIV, Hepatitis B (e.g., Hepatitis B PCR positive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
- Has a history of pneumonitis related to PD-1 blockade that required steroids.
- Has an active infection requiring systemic therapy.
- Has not adequately recovered from major surgery or has ongoing surgical complications
- Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Subjects who have had an allogeneic hematopoietic transplant greater than 5 years ago are eligible as long as there are no symptoms of GVHD.)
- Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Heiko Schoder, MD contact
10 sites in 1 country
United States10 sites, 10 recruiting
- Recruiting
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
Alison Moskowitz, MD, 212-639-4839
- Recruiting
Memorial Sloan Kettering Cancer Center @ Commack
Commack, New York, 11725
Alison Moskowitz, MD, 212-639-4839
- Not yet recruiting
City of Hope Cancer Center (Data Collection Only)
Duarte, California, 91010
Matthew Mei, MD, 626-275-8064
- Recruiting
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Alison Moskowitz, MD, 212-639-4839
- Recruiting
University of Miami (Data Collection Only)
Miami, Florida, 33136
Craig Moskowitz, MD, 305-243-5302
- Recruiting
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Alison Moskowitz, MD, 212-639-4839
- Recruiting
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Alison Moskowitz, MD, 212-639-4839
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Alison Moskowitz, MD, 212-639-4839
Heiko Schoder, MD, 212-639-2079
- Recruiting
Stanford University Medical Center
Stanford, California, 94305-5408
Ranjana Advani, MD, 650-498-6000
- Recruiting
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
Alison Moskowitz, MD, 212-639-4839
About this study
Official title: Phase II Study of Second-line Pembrolizumab Plus GVD for Relapsed or Refractory Hodgkin Lymphoma
The purpose of this study is to test any good and bad effects of the study drug, pembrolizumab, in combination with GVD in the treatment of Hodgkin lymphoma.
- Being tested
- pembrolizumab, gemcitabine, vinorelbine, liposomal doxorubicin, Stem cell mobilization and collection
- Keywords
- Pembrolizumab, GVD, 18-160
- Medical subject headings
- Hodgkin Disease, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pembrolizumabDrug
Age 10-17: 2mg/kg (cap at 200mg), Age ≥ 18: 200 mg (flat) ,Day 1 of each 3 week cycle IV infusion 2-4 cycles (pre-ASCT)
gemcitabineDrug
1000mg/m^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles
vinorelbineDrug
20mg/m^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles
liposomal doxorubicinDrug
15mg/m^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles
Stem cell mobilization and collectionProcedure or surgery
Stem cell mobilization and collection will be performed as per standard MSKCC guidelines after 2-4 cycles of pembrolizumab-GVD.
Involved-site radiation therapyRadiation
Involved-site radiation therapy (ISRT) Patients with limited sites of disease prior to initiation of pembro-GVD are eligible to receive ISRT prior to ASCT or with pembrolizumab maintenance. n. ISRT to nodal based disease should be delivered in line with the guidelines provided by the International Lymphoma Radiation Oncology Group.
| Study group | Role | What they receive |
|---|---|---|
| Safety Window and DLT definition (Part 1) | Experimental | 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. Receives: Drug: pembrolizumab; Drug: gemcitabine; Drug: vinorelbine; Drug: liposomal doxorubicin; Procedure: Stem cell mobilization and collection |
| Safety monitoring beyond after completion of safety window (PART 1) | Experimental | 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 Receives: Drug: pembrolizumab; Drug: gemcitabine; Drug: vinorelbine; Drug: liposomal doxorubicin; Procedure: Stem cell mobilization and collection |
| Autologous Stem Cell Transplant (ASCT) (PARTS 1 and 3) | Experimental | Stem cell mobilization and collection will be performed as per institutional guidelines after 2-4 cycles of pembrolizumab-GVD. Receives: Drug: pembrolizumab; Drug: gemcitabine; Drug: vinorelbine; Drug: liposomal doxorubicin; Procedure: Stem cell mobilization and collection |
| Pembrolizumab maintenance (PART 2) | Experimental | 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. Receives: Drug: pembrolizumab; Drug: gemcitabine; Drug: vinorelbine; Drug: liposomal doxorubicin; Procedure: Stem cell mobilization and collection |
| Pembrolizumab maintenance, third-line therapy, and HDT/ASCT (PART 3A) | Experimental | 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. Receives: Drug: pembrolizumab; Drug: gemcitabine; Drug: vinorelbine; Drug: liposomal doxorubicin; Procedure: Stem cell mobilization and collection |
| Involved-site radiation therapy (ISRT) (PART 3B) | Experimental | Patients with limited sites of disease prior to initiation of pembro-GVD are eligible to receive ISRT prior to ASCT with pembrolizumab maintenance. Receives: Drug: pembrolizumab; Drug: gemcitabine; Drug: vinorelbine; Drug: liposomal doxorubicin; Procedure: Stem cell mobilization and collection; Radiation: Involved-site radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response rate (part 1)
Response to pembrolizumab-GVD will be assessed using the RECIL criteria.
Measured: 2 years
Assess freedom from disease at 5 years (part 3)
A disease event will be defined as disease relapse after transplant or after maintenance if transplant does not occur, death, or loss to follow-up before the 5-year follow-up period ends.
Measured: 5 years
Secondary outcomes (1)
Evaluate the 2-year PFS rate (part 2)
Only patients who receive the Pembrolizumab maintenance regime will be considered evaluable for 2-year PFS and OS rates.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2018
- Study start1 Aug 2018
- Primary completionAug 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- This is a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in transplant eligible patients with relapsed or refractory Hodgkin lymphoma following failure of 1-line of multi-agent chemotherapy.
- Masking
- None (open label)
- Enrolment
- 257 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Alison Moskowitz, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03618550
- Sponsor's protocol ID
- 18-160
- Status last verified
- Oct 2026
- First submitted
- 30 Jul 2018
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Moskowitz AJ, Shah G, Schoder H, Ganesan N, Drill E, Hancock H, Davey T, Perez L, Ryu S, Sohail S, Santarosa A, Galasso N, Neuman R, Liotta B, Blouin W, Kumar A, Lahoud O, Batlevi CL, Hamlin P, Straus DJ, Rodriguez-Rivera I, Owens C, Caron P, Intlekofer AM, Hamilton A, Horwitz SM, Falchi L, Joffe E, Johnson W, Lee C, Palomba ML, Noy A, Matasar MJ, Pongas G, Salles G, Vardhana S, Sanin BW, von Keudell G, Yahalom J, Dogan A, Zelenetz AD, Moskowitz CH. Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma. J Clin Oncol. 2021 Oct 1;39(28):3109-3117. doi: 10.1200/JCO.21.01056. Epub 2021 Jun 25.
PubMed 34170745Ma S, Spinner MA. Optimizing the Role of Checkpoint Inhibitors in the Management of Hodgkin Lymphoma. J Natl Compr Canc Netw. 2026 Feb;24(2):e257125. doi: 10.6004/jnccn.2025.7125.
PubMed 41698326