Second-Line Pembrolizumab in Combination with Gemcitabine, Vinorelbine, and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients with Relapsed or Refractory Hodgkin Lymphoma

Status: Active

Description

This phase II trial studies the side effects and how well pembrolizumab in combination with gemcitabine, vinorelbine, and pegylated liposomal doxorubicin hydrochloride work in treating patients with Hodgkin lymphoma that has come back or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as gemcitabine, vinorelbine, and pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab, gemcitabine, vinorelbine, and pegylated liposomal doxorubicin hydrochloride may work better at treating Hodgkin lymphoma.

Eligibility Criteria

Inclusion Criteria

  • Histologic diagnosis 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.
  • Have measurable disease based on Response Evaluation Criteria in Lymphoma (RECIL).
  • 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%.
  • 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.
  • 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]).

Locations & Contacts

Florida

Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: In review
Contact: Craig Howard Moskowitz
Phone: 305-243-5302

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Alison J. Moskowitz
Phone: 212-639-4839
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Alison J. Moskowitz
Phone: 212-639-4839
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Alison J. Moskowitz
Phone: 212-639-4839

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Alison J. Moskowitz
Phone: 212-639-4839
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Alison J. Moskowitz
Phone: 212-639-4839
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Alison J. Moskowitz
Phone: 212-639-4839
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Alison J. Moskowitz
Phone: 212-639-4839

Trial Objectives and Outline

PRIMARY OBJECTIVES:

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)

SECONDARY OBJECTIVES:

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 treatment response according to lymphoma response to immunomodulatory therapy criteria (LYRIC) criteria.

EXPLORATORY OBJECTIVES:

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, and 3 and 9 months following ASCT 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.

OUTLINE:

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.

After completion of study treatment, patients are followed up every 3 months for up to 2 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Alison J. Moskowitz

Trial IDs

Primary ID 18-160
Secondary IDs NCI-2018-01802
Clinicaltrials.gov ID NCT03618550