Clinical trial NCT04920617: DPX-Survivac and Pembrolizumab With and Without Intermittent Low-Dose Cyclophosphamide, in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Official title: A Phase 2b, Open-label, Multicenter, Randomized Parallel-Group, Two-Stage, Study of an Immunotherapeutic Treatment DPX-Survivac and Pembrolizumab, With and Without Intermittent Low-Dose Cyclophosphamide, in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (VITALIZE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Relapsed Diffuse Large B-cell Lymphoma
Refractory Diffuse Large B-cell Lymphoma
Keywords: Immunotherapy
T cell activation
DLBCL
Anti-PD-1
CAR-T ineligible
ASCT ineligible
Lead sponsor: ImmunoVaccine Technologies, Inc. (IMV Inc.)
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-06-10
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key 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.

Key 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

Primary outcomes:
measure: Objective response rate (ORR) in each of the study arms
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Rate of Adverse Events using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in each of the study arms
timeFrame: Approximately 24 months
measure: Duration of response (DOR) in each of the study arms
timeFrame: Approximately 24 months
measure: Time to response in each of the study arms
timeFrame: Approximately 24 months
measure: Progression-Free Survival in each of the study arms
timeFrame: Approximately 48 months
measure: Disease control rate (DCR) in each of the study arms
timeFrame: Approximately 24 months
measure: Complete response (CR) rate in each of the study arms
timeFrame: Approximately 24 months
measure: Changes in Patient Reported Outcomes using the FACT-Lym Assessment
timeFrame: Approximately 24 months
measure: Changes in Patient Reported Outcomes using the EQ-5D-5L Assessment
timeFrame: Approximately 24 months
Other outcomes:
measure: Objective Response Rate (ORR) based on PD-L1 expression
timeFrame: Approximately 24 months
measure: Time to next treatment (TTNT) in each of the study arms
timeFrame: Approximately 48 months
measure: Overall survival (OS) in each of the study arms
timeFrame: Approximately 48 months
measure: Time to second objective disease progression (PFS2) in each of the study arms
timeFrame: Approximately 48 months
measure: Cell mediated immune response
timeFrame: Approximately 24 months
measure: Changes in immune cell infiltration in tumor biopsies
timeFrame: Approximately 24 months
Locations:
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care Medical Group
state: California
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital
state: Florida
city: Hollywood
country: United States
facility: BRCR Medical Center Inc.
state: Florida
city: Plantation
country: United States
facility: BRCR Medical Center Inc.
state: Florida
city: Saint Petersburg
country: United States
facility: Comprehensive Hematology and Oncology
state: Florida
city: Atlanta
country: United States
facility: Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Health Melvin and Bren Simon Cancer Center
state: Indiana
city: New Orleans
country: United States
facility: Tulane Cancer Center Office of Clinical Research
state: Louisiana
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists
state: Nebraska
city: Santa Fe
country: United States
facility: Christus St. Vincent Regional Cancer Center
state: New Mexico
city: Greenville
country: United States
facility: Brody School of Medicine at East Carolina University
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny Health Network (AHN) West Penn Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital - McGlinn Cancer Institute
state: Pennsylvania
city: Watertown
country: United States
facility: Prairie Lakes Health Care System
state: South Dakota
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Epworth Freemasons Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Westmead
country: Australia
facility: Westmead Hospital
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Center
state: Saskatchewan
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Nancy
country: France
facility: Centre d'Oncologie de Gentilly
city: Nantes
country: France
facility: Hôpital Privé du Confluent
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Hôpital de la Pitié-Salpêtrière
city: Paris
country: France
facility: Hôpital Necker
city: Pessac
country: France
facility: CHU Bordeaux- Hôpital Haut Lévêque
city: Périgueux
country: France
facility: Centre Hospitalier de Périgueux
city: Saint-Quentin
country: France
facility: Centre Hospitalier de Saint-Quentin
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ
city: Nyíregyháza
country: Hungary
facility: SzSzBM Korhazak es Egyetemi Oktatokorhaz
city: Auckland
country: New Zealand
facility: North Shore Hospital
state: Auckland Province
city: Palmerston North
country: New Zealand
facility: Palmerston North Hospital
state: Manawatu
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o. o.
city: Legnica
country: Poland
facility: Wojewódzki Szpital Specjalistyczny w Legnicy
city: Olsztyn
country: Poland
facility: SP ZOZ MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie
city: Skórzewo
country: Poland
facility: Centrum Medyczne Pratia Poznań
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii, Skłodowskiej-Curie
city: Bucharest
country: Romania
facility: Bucharest Oncology Institute "Prof.Dr.Al. Trestioreanu"
city: Cluj-Napoca
country: Romania
facility: The Oncology Institute "Prof. Dr. Ion Chiricuţă" I.O.C.H.
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Sremska Kamenica
country: Serbia
facility: Oncology Institute of Vojvodina
city: Zemun
country: Serbia
facility: Clinical Hospital Center Zemun
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
Study officials:
References: