DPX-Survivac and Pembrolizumab With and Without Intermittent Low-Dose Cyclophosphamide, in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
- Conditions
- Relapsed Diffuse Large B-cell LymphomaRefractory Diffuse Large B-cell Lymphoma
- Interventions
- Registration Number
- NCT04920617
- Lead Sponsor
- ImmunoVaccine Technologies, Inc. (IMV Inc.)
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 102
- 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.
Key
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: DPX-Survivac, pembrolizumab, CPA 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. Arm 1: DPX-Survivac, pembrolizumab, CPA 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. CPA will be self-administered 50 mg BID for 7 days on and 7 days off starting on D0. Arm 2: DPX-Survivac, pembrolizumab 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. Arm 1: DPX-Survivac, pembrolizumab, CPA DPX-Survivac 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. Arm 2: DPX-Survivac, pembrolizumab DPX-Survivac 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.
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) in each of the study arms Approximately 24 months Centrally evaluated using Lugano (2014)
- Secondary Outcome Measures
Name Time Method Rate of Adverse Events using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in each of the study arms Approximately 24 months Time to response in each of the study arms Approximately 24 months Centrally evaluated using Lugano (2014)
Duration of response (DOR) in each of the study arms Approximately 24 months Centrally evaluated using Lugano (2014)
Progression-Free Survival in each of the study arms Approximately 48 months Centrally evaluated using Lugano (2014)
Complete response (CR) rate in each of the study arms Approximately 24 months Centrally evaluated using Lugano (2014)
Changes in Patient Reported Outcomes using the FACT-Lym Assessment Approximately 24 months The FACT-Lym is a validated questionnaire that consists of a 27-item general core questionnaire (i.e., Functional Assessment of Cancer Therapy - General \[FACT-G\]) and a 15-item disease-specific questionnaire (Lymphoma Subscale).
Disease control rate (DCR) in each of the study arms Approximately 24 months Centrally evaluated using Lugano (2014)
Changes in Patient Reported Outcomes using the EQ-5D-5L Assessment Approximately 24 months The EQ-5D-5L is a 5-item measure that can be used to describe and value current overall health consisting of 5 items assessing mobility, self care, usual activities, pain/discomfort, and anxiety/depression.
Trial Locations
- Locations (49)
Boca Raton Regional Hospital
🇺🇸Boca Raton, Florida, United States
BRCR Medical Center Inc.
🇺🇸Plantation, Florida, United States
Blood and Marrow Transplant Group of Georgia
🇺🇸Atlanta, Georgia, United States
CHU Bordeaux- Hôpital Haut Lévêque
🇫🇷Pessac, France
Centre Hospitalier de Périgueux
🇫🇷Périgueux, France
Palmerston North Hospital
🇳🇿Palmerston North, Manawatu, New Zealand
North Shore Hospital
🇳🇿Auckland, Auckland Province, New Zealand
Hospital Universitario de Burgos
🇪🇸Burgos, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
The Oncology Institute "Prof. Dr. Ion Chiricuţă" I.O.C.H.
🇷🇴Cluj-Napoca, Romania
Hôpital Necker
🇫🇷Paris, France
Hospital Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Szpitale Pomorskie Sp. z o. o.
🇵🇱Gdynia, Poland
Compassionate Cancer Care Medical Group
🇺🇸Fountain Valley, California, United States
Oncology Hematology West, PC dba Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Tulane Cancer Center Office of Clinical Research
🇺🇸New Orleans, Louisiana, United States
Brody School of Medicine at East Carolina University
🇺🇸Greenville, North Carolina, United States
Christus St. Vincent Regional Cancer Center
🇺🇸Santa Fe, New Mexico, United States
Gabrail Cancer Center Research
🇺🇸Canton, Ohio, United States
University of Toledo Medical Center
🇺🇸Toledo, Ohio, United States
Toledo Clinic Cancer Center
🇺🇸Toledo, Ohio, United States
Allegheny Health Network (AHN) West Penn Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Reading Hospital - McGlinn Cancer Institute
🇺🇸West Reading, Pennsylvania, United States
Prairie Lakes Health Care System
🇺🇸Watertown, South Dakota, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Box Hill Hospital
🇦🇺Melbourne, Victoria, Australia
Westmead Hospital
🇦🇺Westmead, Australia
Hôpital Avicenne
🇫🇷Bobigny, France
Saskatoon Cancer Center
🇨🇦Saskatoon, Saskatchewan, Canada
Centre d'Oncologie de Gentilly
🇫🇷Nancy, France
Hôpital Saint-Antoine
🇫🇷Paris, France
Hôpital Privé du Confluent
🇫🇷Nantes, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Indiana University Health Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Hôpital de la Pitié-Salpêtrière
🇫🇷Paris, France
Centre Hospitalier de Saint-Quentin
🇫🇷Saint-Quentin, France
Comprehensive Hematology and Oncology
🇺🇸Saint Petersburg, Florida, United States
Debreceni Egyetem Klinikai Központ
🇭🇺Debrecen, Hungary
Narodowy Instytut Onkologii im. Marii, Skłodowskiej-Curie
🇵🇱Warszawa, Poland
Bucharest Oncology Institute "Prof.Dr.Al. Trestioreanu"
🇷🇴Bucharest, Romania
University Clinical Center of Serbia
🇷🇸Belgrade, Serbia
University Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
Clinical Hospital Center Zemun
🇷🇸Zemun, Serbia
SP ZOZ MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie
🇵🇱Olsztyn, Poland
Centrum Medyczne Pratia Poznań
🇵🇱Skórzewo, Poland
SzSzBM Korhazak es Egyetemi Oktatokorhaz
🇭🇺Nyíregyháza, Hungary
Oncology Institute of Vojvodina
🇷🇸Sremska Kamenica, Serbia
Wojewódzki Szpital Specjalistyczny w Legnicy
🇵🇱Legnica, Poland
Epworth Freemasons Hospital
🇦🇺Melbourne, Victoria, Australia