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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03618550

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Locations

Arm

Anticipated Duration (Months)

7.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Lymphoma Relapsed or Refractory Hodgkin Lymphoma	Drug: pembrolizumab Drug: gemcitabine Drug: vinorelbine Drug: liposomal doxorubicin Procedure: Stem cell mobilization and collection	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in transplant eligible patients with relapsed or refractory Hodgkin lymphoma following failure of 1-line of multi-agent chemotherapy.This is a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in transplant eligible patients with relapsed or refractory Hodgkin lymphoma following failure of 1-line of multi-agent chemotherapy.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 1, 2018

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

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

Arm

Intervention/Treatment

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).

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)

Drug: gemcitabine

1000mg/m^2 Days 1 and 8 of each 3 week cycle IV infusion 2-4 cycles

Drug: vinorelbine

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.

Outcome Measures

Primary Outcome Measures

complete response rate [2 years]
Response to pembrolizumab-GVD will be assessed using the RECIL criteria.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
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

Locations

	Site	City	State	Country	Postal Code
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