DPX-Survivac and Pembrolizumab With and Without Intermittent Low-Dose Cyclophosphamide, in Subjects With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Refractory Diffuse Large B-cell Lymphoma Clinical Trial

— VITALIZE  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04920617
• Other study ID #: P1605-SUR-D23
• Secondary ID: KEYNOTE-C54
• Status: Recruiting
• Phase: Phase 2
• Start date: June 18, 2021
• Est. completion date: April 2025

Study information

• Verified date: August 2022
• Source: ImmunoVaccine Technologies, Inc. (IMV Inc.)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 102
• Est. completion date: April 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Refractory Diffuse Large B-cell Lymphoma
• Relapsed Diffuse Large B-cell Lymphoma

Intervention

Drug:
• DPX-Survivac
SC injection on D7 and D28, then every 8 weeks
• Pembrolizumab
IV infusion every 3 weeks
• CPA
50 mg twice daily, week on then week off

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Box Hill Hospital	Melbourne	Victoria
Australia	Epworth Freemasons Hospital	Melbourne	Victoria
Australia	Westmead Hospital	Westmead
Canada	Saskatoon Cancer Center	Saskatoon	Saskatchewan
France	Hôpital Avicenne	Bobigny
France	Centre d'Oncologie de Gentilly	Nancy
France	Hôpital Privé du Confluent	Nantes
France	Centre Antoine Lacassagne	Nice
France	Hôpital de la Pitié-Salpêtrière	Paris
France	Hôpital Necker	Paris
France	Hôpital Saint-Antoine	Paris
France	Centre Hospitalier de Périgueux	Périgueux
France	CHU Bordeaux- Hôpital Haut Lévêque	Pessac
France	Centre Hospitalier de Saint-Quentin	Saint-Quentin
Hungary	Debreceni Egyetem Klinikai Központ	Debrecen
Hungary	SzSzBM Korhazak es Egyetemi Oktatokorhaz	Nyíregyháza
New Zealand	North Shore Hospital	Auckland	Auckland Province
New Zealand	Palmerston North Hospital	Palmerston North	Manawatu
Poland	Szpitale Pomorskie Sp. z o. o.	Gdynia
Poland	Wojewódzki Szpital Specjalistyczny w Legnicy	Legnica
Poland	SP ZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn
Poland	Centrum Medyczne Pratia Poznan	Skórzewo
Poland	Narodowy Instytut Onkologii im. Marii, Sklodowskiej-Curie	Warszawa
Romania	Bucharest Oncology Institute "Prof.Dr.Al. Trestioreanu"	Bucharest
Romania	The Oncology Institute "Prof. Dr. Ion Chiricuta" I.O.C.H.	Cluj-Napoca
Serbia	University Clinical Center of Serbia	Belgrade
Serbia	University Clinical Center Kragujevac	Kragujevac
Serbia	Oncology Institute of Vojvodina	Sremska Kamenica
Serbia	Clinical Hospital Center Zemun	Zemun
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario de Burgos	Burgos
Spain	Hospital Universitario Virgen del Rocío	Sevilla
United States	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Compassionate Cancer Care Medical Group	Fountain Valley	California
United States	Brody School of Medicine at East Carolina University	Greenville	North Carolina
United States	BRCR Medical Center Inc.	Hollywood	Florida
United States	Indiana University Health Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Tulane Cancer Center Office of Clinical Research	New Orleans	Louisiana
United States	Oncology Hematology West, PC dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	Allegheny Health Network (AHN) West Penn Hospital	Pittsburgh	Pennsylvania
United States	BRCR Medical Center Inc.	Plantation	Florida
United States	Comprehensive Hematology and Oncology	Saint Petersburg	Florida
United States	Christus St. Vincent Regional Cancer Center	Santa Fe	New Mexico
United States	Toledo Clinic Cancer Center	Toledo	Ohio
United States	University of Toledo Medical Center	Toledo	Ohio
United States	Prairie Lakes Health Care System	Watertown	South Dakota
United States	Reading Hospital - McGlinn Cancer Institute	West Reading	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
ImmunoVaccine Technologies, Inc. (IMV Inc.)	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Hungary,  New Zealand,  Poland,  Romania,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Objective Response Rate (ORR) based on PD-L1 expression	Centrally evaluated using Lugano (2014) and central assessment of PD-L1 using validated 22C3 assay	Approximately 24 months
Other	Time to next treatment (TTNT) in each of the study arms		Approximately 48 months
Other	Overall survival (OS) in each of the study arms		Approximately 48 months
Other	Time to second objective disease progression (PFS2) in each of the study arms		Approximately 48 months
Other	Cell mediated immune response		Approximately 24 months
Other	Changes in immune cell infiltration in tumor biopsies		Approximately 24 months
Primary	Objective response rate (ORR) in each of the study arms	Centrally evaluated using Lugano (2014)	Approximately 24 months
Secondary	Rate of Adverse Events using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in each of the study arms		Approximately 24 months
Secondary	Duration of response (DOR) in each of the study arms	Centrally evaluated using Lugano (2014)	Approximately 24 months
Secondary	Time to response in each of the study arms	Centrally evaluated using Lugano (2014)	Approximately 24 months
Secondary	Progression-Free Survival in each of the study arms	Centrally evaluated using Lugano (2014)	Approximately 48 months
Secondary	Disease control rate (DCR) in each of the study arms	Centrally evaluated using Lugano (2014)	Approximately 24 months
Secondary	Complete response (CR) rate in each of the study arms	Centrally evaluated using Lugano (2014)	Approximately 24 months
Secondary	Changes in Patient Reported Outcomes using the FACT-Lym Assessment	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).	Approximately 24 months
Secondary	Changes in Patient Reported Outcomes using the EQ-5D-5L Assessment	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.	Approximately 24 months