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RecruitingInterventionalPhase 2

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)

NCT ID: NCT04920617Sponsor: ImmunoVaccine Technologies, Inc. (IMV Inc.)Last updated: 2023-04-07

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.

Arms & interventions

  • DrugDPX-Survivac

    SC injection on D7 and D28, then every 8 weeks

  • DrugPembrolizumab

    IV infusion every 3 weeks

  • DrugCPA

    50 mg twice daily, week on then week off

Outcome measures

Primary

  • Objective response rate (ORR) in each of the study arms

    Centrally evaluated using Lugano (2014)

    Time frame: 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

    Time frame: Approximately 24 months

  • Duration of response (DOR) in each of the study arms

    Time frame: Approximately 24 months

  • Time to response in each of the study arms

    Time frame: Approximately 24 months

  • Progression-Free Survival in each of the study arms

    Time frame: Approximately 48 months

  • Disease control rate (DCR) in each of the study arms

    Time frame: Approximately 24 months

  • Complete response (CR) rate in each of the study arms

    Time frame: Approximately 24 months

  • Changes in Patient Reported Outcomes using the FACT-Lym Assessment

    Time frame: Approximately 24 months

  • Changes in Patient Reported Outcomes using the EQ-5D-5L Assessment

    Time frame: Approximately 24 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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

Study locations (17)

Compassionate Cancer Care Medical Group

Fountain Valley, California, 92708

Recruiting
Haresh Jhangiani, MD · Contact
Eric Lee, MD · Principal Investigator

Boca Raton Regional Hospital

Boca Raton, Florida, 33486

Withdrawn

BRCR Medical Center Inc.

Hollywood, Florida, 33021

Withdrawn

BRCR Medical Center Inc.

Plantation, Florida, 33322

Withdrawn

Comprehensive Hematology and Oncology

St. Petersburg, Florida, 33709

Withdrawn

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342

Recruiting
Melhem Solh, MD · Contact
Melhem Solh, MD · Principal Investigator

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202

Recruiting
Jill Weisenbach · Contact
Michael Robertson, MD · Principal Investigator

Tulane Cancer Center Office of Clinical Research

New Orleans, Louisiana, 70112

Recruiting
Leta Ko · Contact
Nakhle Saba, MD · Principal Investigator

Oncology Hematology West, PC dba Nebraska Cancer Specialists

Omaha, Nebraska, 68130

Recruiting
Stefano Tarantolo, MD · Principal Investigator

Christus St. Vincent Regional Cancer Center

Santa Fe, New Mexico, 87505

Recruiting
Karen LoRusso, MD · Principal Investigator

Brody School of Medicine at East Carolina University

Greenville, North Carolina, 27834

Recruiting
Denise Brigham · Contact
Darla Liles, MD · Principal Investigator

Gabrail Cancer Center Research

Canton, Ohio, 44718

Withdrawn

University of Toledo Medical Center

Toledo, Ohio, 43614

Withdrawn

Toledo Clinic Cancer Center

Toledo, Ohio, 43623

Recruiting
Rex Mowat, MD · Principal Investigator

Allegheny Health Network (AHN) West Penn Hospital

Pittsburgh, Pennsylvania, 15224

Recruiting
Diane Pershing · Contact
Rich Wonder · Contact
Yazan Samhouri, MD · Principal Investigator

Reading Hospital - McGlinn Cancer Institute

West Reading, Pennsylvania, 19611

Recruiting
Terrence Cescon, MD · Principal Investigator

Prairie Lakes Health Care System

Watertown, South Dakota, 57201

Withdrawn