Phase II Study of Second- Line Pembrolizumab Plus GVD for Relapsed or Refractory Hodgkin Lymphoma
Phase 2
Recruiting
- Conditions
- Hodgkin LymphomaRelapsed or Refractory Hodgkin Lymphoma
- Interventions
- Procedure: Stem cell mobilization and collection
- Registration Number
- NCT03618550
- Lead Sponsor
- Memorial Sloan Kettering Cancer Center
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 257
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.
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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.
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Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
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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.
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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).
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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.
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Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
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Has an active infection requiring systemic therapy.
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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.)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pembrolizumab maintenance (PART 2) liposomal doxorubicin 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. Autologous Stem Cell Transplant (ASCT) (PARTS 1 and 3) liposomal doxorubicin Stem cell mobilization and collection will be performed as per institutional guidelines after 2-4 cycles of pembrolizumab-GVD. Safety monitoring beyond after completion of safety window (PART 1) liposomal doxorubicin 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 Pembrolizumab maintenance, third-line therapy, and HDT/ASCT (PART 3) liposomal doxorubicin 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. Involved-site radiation therapy (ISRT) (PART 3) liposomal doxorubicin Patients with limited sites of disease prior to initiation of pembro-GVD are eligible to receive ISRT prior to ASCT with pembrolizumab maintenance. Safety Window and DLT definition (Part 1) pembrolizumab 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. Safety Window and DLT definition (Part 1) gemcitabine 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. Safety Window and DLT definition (Part 1) Stem cell mobilization and collection 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. Safety monitoring beyond after completion of safety window (PART 1) pembrolizumab 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 Safety Window and DLT definition (Part 1) vinorelbine 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. Safety Window and DLT definition (Part 1) liposomal doxorubicin 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. Safety monitoring beyond after completion of safety window (PART 1) gemcitabine 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 Safety monitoring beyond after completion of safety window (PART 1) vinorelbine 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 Safety monitoring beyond after completion of safety window (PART 1) Stem cell mobilization and collection 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 Autologous Stem Cell Transplant (ASCT) (PARTS 1 and 3) pembrolizumab Stem cell mobilization and collection will be performed as per institutional guidelines after 2-4 cycles of pembrolizumab-GVD. Autologous Stem Cell Transplant (ASCT) (PARTS 1 and 3) gemcitabine Stem cell mobilization and collection will be performed as per institutional guidelines after 2-4 cycles of pembrolizumab-GVD. Autologous Stem Cell Transplant (ASCT) (PARTS 1 and 3) vinorelbine Stem cell mobilization and collection will be performed as per institutional guidelines after 2-4 cycles of pembrolizumab-GVD. Autologous Stem Cell Transplant (ASCT) (PARTS 1 and 3) Stem cell mobilization and collection Stem cell mobilization and collection will be performed as per institutional guidelines after 2-4 cycles of pembrolizumab-GVD. Pembrolizumab maintenance (PART 2) pembrolizumab 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. Pembrolizumab maintenance (PART 2) gemcitabine 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. Pembrolizumab maintenance (PART 2) vinorelbine 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. Pembrolizumab maintenance (PART 2) Stem cell mobilization and collection 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. Pembrolizumab maintenance, third-line therapy, and HDT/ASCT (PART 3) pembrolizumab 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. Pembrolizumab maintenance, third-line therapy, and HDT/ASCT (PART 3) gemcitabine 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. Pembrolizumab maintenance, third-line therapy, and HDT/ASCT (PART 3) vinorelbine 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. Pembrolizumab maintenance, third-line therapy, and HDT/ASCT (PART 3) Stem cell mobilization and collection 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. Involved-site radiation therapy (ISRT) (PART 3) pembrolizumab Patients with limited sites of disease prior to initiation of pembro-GVD are eligible to receive ISRT prior to ASCT with pembrolizumab maintenance. Involved-site radiation therapy (ISRT) (PART 3) gemcitabine Patients with limited sites of disease prior to initiation of pembro-GVD are eligible to receive ISRT prior to ASCT with pembrolizumab maintenance. Involved-site radiation therapy (ISRT) (PART 3) vinorelbine Patients with limited sites of disease prior to initiation of pembro-GVD are eligible to receive ISRT prior to ASCT with pembrolizumab maintenance. Involved-site radiation therapy (ISRT) (PART 3) Stem cell mobilization and collection Patients with limited sites of disease prior to initiation of pembro-GVD are eligible to receive ISRT prior to ASCT with pembrolizumab maintenance.
- Primary Outcome Measures
Name Time Method Complete response rate (part 1) 2 years Response to pembrolizumab-GVD will be assessed using the RECIL criteria.
- Secondary Outcome Measures
Name Time Method Evaluate the 2-year PFS rate (part 2) 2 years Only patients who receive the Pembrolizumab maintenance regime will be considered evaluable for 2-year PFS and OS rates.
Trial Locations
- Locations (8)
University of Miami
🇺🇸Miami, Florida, United States
Memorial Sloan Kettering Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
🇺🇸Montvale, New Jersey, United States
Memorial Sloan Kettering Cancer Center @ Commack
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Westchester
🇺🇸Harrison, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Nassau
🇺🇸Uniondale, New York, United States