Phase II Study of Second- Line Pembrolizumab Plus GVD for Relapsed or Refractory Hodgkin Lymphoma

Study Overview
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Brief Summary
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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.

Official Title
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Phase II Study of Second-line Pembrolizumab Plus GVD for Relapsed or Refractory Hodgkin Lymphoma

Conditions
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Hodgkin Lymphoma, Relapsed or Refractory Hodgkin Lymphoma

Intervention / Treatment
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* Drug: pembrolizumab
* Drug: gemcitabine
* Drug: vinorelbine
* Drug: liposomal doxorubicin
* Procedure: Stem cell mobilization and collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic diagnosis of classical Hodgkin's lymphoma. Primary refractory or relapsed disease proven by excisional or core needle biopsy at enrolling institution. Relapse or refractory disease following 1 line of multi-agent chemotherapy. Be willing and able to provide written informed consent/assent for the trial. Be ≥ 18 years of age on day of signing informed consent. 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. Absolute neutrophil count (ANC) ≥1000 /mcL Platelets ≥50,000 / mcL Hemoglobin ≥8 g/dL Serum creatinine OR ≤1.5 X upper limit of normal (ULN) OR Measured or calculateda creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN 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 Hemoglobin-adjusted diffusing capacity for carbon monoxide ≥50% (If unadjusted DLCO is >/= 50% then there is no need to calculate adjusted) Ejection fraction ≥45% Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. Female subjects of childbearing potential must be willing to use an adequate method of contraception Male subjects of childbearing potential must agree to use an adequate method of contraception. Exclusion Criteria: Received more than 1 prior treatment (combined modality therapy represents 1 treatment) for Hodgkin Lymphoma 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 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 (non-infectious) pneumonitis that required steroids or has current pneumonitis. Has an active infection requiring systemic therapy. 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.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pembrolizumab plus GVD<br>Part 1: Patients will receive 2-4 cycles of pembrolizumab plus GVD Part 2: up to 40 patients will be enrolled onto an expansion cohort. On the expansion, patients who achieve CR to 4 cycles of pembro-GVD will receive 13 cycles of pembrolizumab maintenance (instead of HDT/ASCT). | Drug: pembrolizumab<br>* 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)<br>Drug: gemcitabine<br>* 1000mg/m^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles<br>Drug: vinorelbine<br>* 20mg/m^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles<br>Drug: liposomal doxorubicin<br>* 15mg/m^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles<br>Procedure: Stem cell mobilization and collection<br>* Stem cell mobilization and collection will be performed as per standard MSKCC guidelines after 2-4 cycles of pembrolizumab-GVD.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate (part 1) | Response to pembrolizumab-GVD will be assessed using the RECIL criteria. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pembrolizumab, GVD, 18-160