Second-Line Pembrolizumab in Combination with Gemcitabine, Vinorelbine, and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients with Relapsed or Refractory Hodgkin Lymphoma
- Histologic diagnosis of classical Hodgkin’s lymphoma.
- Primary refractory or relapsed disease proven by 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 Eastern Cooperative Oncology Group (ECOG) performance scale.
- Absolute neutrophil count (ANC) >= 1000 /mcL.
- Platelets >= 50,000 / mcL.
- Hemoglobin >= 8 g/dL.
- Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) (glomerular filtration rate [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 UL OR =< 3 X ULN for subjects with liver metastases.
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SPGT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases.
- Hemoglobin-adjusted diffusing capacity for carbon monoxide >= 50%. (If unadjusted carbon monoxide diffusing capability test [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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known active human immunodeficiency virus (HIV), hepatitis B (e.g., hepatitis B polymerase chain reaction [PCR] positive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected).
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not 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 graft-versus-host disease [GVHD]).
I. Establish the safety of pre-autologous stem-cell transplantation (ASCT) pembrolizumab plus gemcitabine, vinorelbine, and pegylated liposomal doxorubicin hydrochloride (GVD) for relapsed/refractory Hodgkin lymphoma. (safety window)
II. Evaluate the complete response rate to pembrolizumab plus GVD in relapsed/refractory Hodgkin lymphoma. (phase II)
I. Evaluate partial response and minor response rate to pembrolizumab plus GVD in relapsed/refractory Hodgkin lymphoma.
II. Evaluate progression free survival and overall survival for patients receiving pembrolizumab-GVD followed by ASCT.
III. Evaluate 2-year progression free survival and overall survival rates for patients receiving pembrolizumab-GVD followed by 13 cycles of pembrolizumab maintenance.
IV. Evaluate treatment response according to lymphoma response to immunomodulatory therapy criteria (LYRIC) criteria.
I. Assess association between serum TARC (Thymus and activation-regulated chemokine/CCL17) levels and progression free survival and achievement of complete response to therapy.
II. Assessment of quantitative fludeoxyglucose F 18 (FDG) positron emission tomography (PET) metrics, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), at baseline, after 2 cycles, and following 4 cycles of treatment and association between complete response to treatment and progression free survival.
III. Assessment of tumor-specific cell-free deoxyribonucleic acid (DNA) at baseline, after 2 cycles and 4 cycles of pembrolizumab plus GVD, cycles 10 and 17 of pembrolizumab maintenance, and 3 and 9 months following ASCT/maintenance and association between complete response to treatment and progression free survival.
IV. Evaluate association between expression of major histocompatibility complex (MHC)-I, MHC-II, beta-2 microglobulin, and 9p24.1 amplification by Reed-Sternberg cells and progression free survival and achievement of complete response to therapy.
Patients receive pembrolizumab intravenously (IV) on day 1, gemcitabine IV, vinorelbine IV, and pegylated liposomal doxorubicin hydrochloride IV on days 1 and day 8, and pegfilgrastim subcutaneously (SC) on day 9. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo ASCT. Patients who do not achieve a complete response after 2 cycles receive an additional 2 cycles, before undergoing ASCT. Patients who achieve a complete response after 4 cycles may receive an additional 13 cycles of pembrolizumab instead of ASCT.
After completion of study treatment, patients are followed up every 3 months for up to 2 years.
Trial Phase Phase II
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
Alison J. Moskowitz
- Primary ID 18-160
- Secondary IDs NCI-2018-01802
- Clinicaltrials.gov ID NCT03618550