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.
Arms and Interventions
|Experimental: pembrolizumab plus GVD|
Part 1: Patients will receive 2-4 cycles of pembrolizumab plus GVD Part 2: an additional 25 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).
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)
1000mg/m^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles
20mg/m^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles
Drug: liposomal doxorubicin
15mg/m^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles
Procedure: Stem cell mobilization and collection
Stem cell mobilization and collection will be performed as per standard MSKCC guidelines after 2-4 cycles of pembrolizumab-GVD.
Primary Outcome Measures
- complete response rate [2 years]
Response to pembrolizumab-GVD will be assessed using the RECIL 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.
Received more than 1 prior treatment (combined modality therapy represents 1 treatment) for Hodgkin Lymphoma
Known pregnancy or breast-feeding.
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.)
Contacts and Locations
|1||University of Miami||Miami||Florida||United States||33136|
|2||Memoral Sloan Kettering Basking Ridge||Basking Ridge||New Jersey||United States||07920|
|3||Memoral Sloan Kettering Monmouth||Middletown||New Jersey||United States||07748|
|4||Memorial Sloan Kettering Bergen||Montvale||New Jersey||United States||07645|
|5||Memorial Sloan Kettering Cancer Center @ Commack||Commack||New York||United States||11725|
|6||Memoral Sloan Kettering Westchester||Harrison||New York||United States||10604|
|7||Memorial Sloan - Kettering Cancer Center||New York||New York||United States||10021|
|8||Memorial Sloan Kettering Cancer Center||New York||New York||United States||10065|
|9||Memorial Sloan Kettering Nassau||Uniondale||New York||United States||11553|
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
- Merck Sharp & Dohme Corp.
- Principal Investigator: Alison Moskowitz, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)None provided.