DPX-Survivac and Pembrolizumab With and Without Intermittent Low-Dose Cyclophosphamide, in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Purpose
This is a Phase 2b, randomized, open label study to assess the safety and efficacy of DPX-Survivac and pembrolizumab, with and without low-dose cyclophosphamide (CPA) in subjects with relapsed or refractory DLBCL.
Conditions
- Relapsed Diffuse Large B-cell Lymphoma
- Refractory Diffuse Large B-cell Lymphoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Adults ≥ 18 years of age who are willing and able to provide written informed consent - Have an ECOG performance status of ≤ 1. Subjects with an ECOG performance status of 2 may be enrolled with Medical Monitor approval. - Pathologically confirmed diagnosis of DLBCL, as defined by the 2016 World Health Organization classification including DLBCL NOS high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, Epstein-barr virus (EBV) positive DLBCL, and T cell rich B cell lymphoma (TCRBCL). Subjects with DLBCL transformed from indolent lymphoma (except for Richter's transformation) are eligible. - Subjects must have progressive disease following at least two (2) lines of prior systemic therapy for DLBCL; prior treatment must have included an anthracycline and rituximab (or another CD20-targeted agent). - Subjects must have failed or be ineligible for ASCT or CAR-T - Have at least one bi-dimensionally measurable lesion per Lugano (2014) - Willing to provide pre-treatment and on-treatment tumor biopsy tissue. - Meet protocol-specified laboratory requirements - Life expectancy > 3 months.
Exclusion Criteria
- Primary CNS lymphoma or active secondary CNS involvement and/or lymphomatous meningitis - Chemotherapy, immunotherapy, major surgery, or investigational agent treatment within 28 days of D0 or 5 half-lives, whichever is shorter - Radiotherapy within 14 days of day 0 - Autologous stem cell transplant (ASCT) within ˂100 days prior to D0 - Chimeric antigen receptor T cell (CAR-T) therapy within ˂28 days prior to D0 - Diagnosis of immunodeficiency disorder or history of active autoimmune disease that has required systemic treatment in the past 2 years - Uncontrolled significant active infections (controlled Hepatitis B, Hepatitis C, or HIV may be eligible) - Prior history of malignancy other than eligible lymphoma sub-types, unless the subject has been free of the disease for ≥ 2 years prior to the start of study treatment
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm 1: DPX-Survivac, pembrolizumab, CPA |
Subjects will receive two 0.5 mL doses of DPX-Survivac three weeks apart followed by up to twelve 0.1 mL doses eight weeks apart. Pembrolizumab will be administered on the first day of every three week cycle at a flat dose of 200 mg. CPA will be self-administered 50 mg BID for 7 days on and 7 days off starting on D0. |
|
|
Experimental Arm 2: DPX-Survivac, pembrolizumab |
Subjects will receive two 0.5 mL doses of DPX-Survivac three weeks apart followed by up to twelve 0.1 mL doses eight weeks apart. Pembrolizumab will be administered on the first day of every three week cycle at a flat dose of 200 mg. Subjects randomized to Arm 2 will not receive CPA. |
|
Recruiting Locations
Compassionate Cancer Care Medical Group
Fountain Valley, California 92708
Fountain Valley, California 92708
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia 30342
Atlanta, Georgia 30342
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana 46202
Indianapolis, Indiana 46202
Tulane Cancer Center Office of Clinical Research
New Orleans, Louisiana 70112
New Orleans, Louisiana 70112
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska 68130
Omaha, Nebraska 68130
Christus St. Vincent Regional Cancer Center
Santa Fe, New Mexico 87505
Santa Fe, New Mexico 87505
Brody School of Medicine at East Carolina University
Greenville, North Carolina 27834
Greenville, North Carolina 27834
Toledo Clinic Cancer Center
Toledo, Ohio 43623
Toledo, Ohio 43623
Allegheny Health Network (AHN) West Penn Hospital
Pittsburgh, Pennsylvania 15224
Pittsburgh, Pennsylvania 15224
Reading Hospital - McGlinn Cancer Institute
West Reading, Pennsylvania 19611
West Reading, Pennsylvania 19611
More Details
- Status
- Recruiting
- Sponsor
- ImmunoVaccine Technologies, Inc. (IMV Inc.)
Study Contact
Detailed Description
This is a Phase 2b, randomized, open label study to assess the safety and efficacy of DPX-Survivac and pembrolizumab, with and without low-dose cyclophosphamide (CPA) in subjects with relapsed or refractory DLBCL. The study will enroll up to 102 subjects. Eligible subjects will be randomized (1:1) to receive: - Arm 1: DPX-Survivac, pembrolizumab and intermittent, low-dose CPA; or, - Arm 2: DPX-Survivac and pembrolizumab All subjects will receive two 0.5 mL doses of DPX-Survivac 3 weeks apart on day 7 (D7) and D28 followed by up to twelve 0.1 mL doses of DPX-Survivac, 8 weeks apart (Q8W). All subjects will receive pembrolizumab intravenously (IV) at a flat dose of 200 mg starting at D7 and on day 1 of each 3-week cycle thereafter (i.e., D28, D49, D70 etc.) (Q3W). For subjects randomized to Arm 1, intermittent oral CPA at a dose of 50 mg twice a day (BID) is administered from D0 to D6 (7 days) followed by 7 days off. This 14-day cycle of "7 days on and 7 days off" will be repeated until the end of study treatment.