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

Hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03618550
• Other study ID #: 18-160
• Status: Recruiting
• Phase: Phase 2
• Start date: August 1, 2018
• Est. completion date: August 2024

Study information

• Verified date: April 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Alison Moskowitz, MD
• Phone: 212-639-4839
• Email: moskowia[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 69
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.)

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma
• Relapsed or Refractory Hodgkin Lymphoma

Intervention

Drug:
• pembrolizumab
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)
• gemcitabine
1000mg/m^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles
• vinorelbine
20mg/m^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles
• 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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Cancer Center @ Commack	Commack	New York
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	University of Miami	Miami	Florida
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	New York	New York
United States	Memorial Sloan Kettering Nassau	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

References & Publications (1)

Moskowitz AJ, Shah G, Schoder H, Ganesan N, Drill E, Hancock H, Davey T, Perez L, Ryu S, Sohail S, Santarosa A, Galasso N, Neuman R, Liotta B, Blouin W, Kumar A, Lahoud O, Batlevi CL, Hamlin P, Straus DJ, Rodriguez-Rivera I, Owens C, Caron P, Intlekofer AM, Hamilton A, Horwitz SM, Falchi L, Joffe E, Johnson W, Lee C, Palomba ML, Noy A, Matasar MJ, Pongas G, Salles G, Vardhana S, Sanin BW, von Keudell G, Yahalom J, Dogan A, Zelenetz AD, Moskowitz CH. Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma. J Clin Oncol. 2021 Oct 1;39(28):3109-3117. doi: 10.1200/JCO.21.01056. Epub 2021 Jun 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rate (part 1)	Response to pembrolizumab-GVD will be assessed using the RECIL criteria.	2 years
Secondary	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

External Links

•   Memorial Sloan Kettering Cancer Center