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

NCT ID: NCT04920617

Last Updated: 2023-04-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-18

Study Completion Date

2025-04-30

Brief Summary

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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

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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.

Conditions

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Relapsed Diffuse Large B-cell Lymphoma Refractory Diffuse Large B-cell Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

DPX-Survivac

Intervention Type DRUG

SC injection on D7 and D28, then every 8 weeks

Pembrolizumab

Intervention Type DRUG

IV infusion every 3 weeks

CPA

Intervention Type DRUG

50 mg twice daily, week on then week off

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.

Group Type EXPERIMENTAL

DPX-Survivac

Intervention Type DRUG

SC injection on D7 and D28, then every 8 weeks

Pembrolizumab

Intervention Type DRUG

IV infusion every 3 weeks

Interventions

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DPX-Survivac

SC injection on D7 and D28, then every 8 weeks

Intervention Type DRUG

Pembrolizumab

IV infusion every 3 weeks

Intervention Type DRUG

CPA

50 mg twice daily, week on then week off

Intervention Type DRUG

Other Intervention Names

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maveropepimut-S MK-3475 Keytruda Intermittent, low-dose cyclophosphamide Procytox Cytoxan

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

ImmunoVaccine Technologies, Inc. (IMV Inc.)

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Compassionate Cancer Care Medical Group

Fountain Valley, California, United States

Site Status RECRUITING

Boca Raton Regional Hospital

Boca Raton, Florida, United States

Site Status WITHDRAWN

BRCR Medical Center Inc.

Hollywood, Florida, United States

Site Status WITHDRAWN

BRCR Medical Center Inc.

Plantation, Florida, United States

Site Status WITHDRAWN

Comprehensive Hematology and Oncology

St. Petersburg, Florida, United States

Site Status WITHDRAWN

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, United States

Site Status RECRUITING

Indiana University Health Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status RECRUITING

Tulane Cancer Center Office of Clinical Research

New Orleans, Louisiana, United States

Site Status RECRUITING

Oncology Hematology West, PC dba Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status RECRUITING

Christus St. Vincent Regional Cancer Center

Santa Fe, New Mexico, United States

Site Status RECRUITING

Brody School of Medicine at East Carolina University

Greenville, North Carolina, United States

Site Status RECRUITING

Gabrail Cancer Center Research

Canton, Ohio, United States

Site Status WITHDRAWN

University of Toledo Medical Center

Toledo, Ohio, United States

Site Status WITHDRAWN

Toledo Clinic Cancer Center

Toledo, Ohio, United States

Site Status RECRUITING

Allegheny Health Network (AHN) West Penn Hospital

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Reading Hospital - McGlinn Cancer Institute

West Reading, Pennsylvania, United States

Site Status RECRUITING

Prairie Lakes Health Care System

Watertown, South Dakota, United States

Site Status WITHDRAWN

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status RECRUITING

Epworth Freemasons Hospital

Melbourne, Victoria, Australia

Site Status RECRUITING

Box Hill Hospital

Melbourne, Victoria, Australia

Site Status RECRUITING

Westmead Hospital

Westmead, , Australia

Site Status RECRUITING

Saskatoon Cancer Center

Saskatoon, Saskatchewan, Canada

Site Status RECRUITING

Hôpital Avicenne

Bobigny, , France

Site Status RECRUITING

Centre d'Oncologie de Gentilly

Nancy, , France

Site Status RECRUITING

Hôpital Privé du Confluent

Nantes, , France

Site Status RECRUITING

Centre Antoine Lacassagne

Nice, , France

Site Status RECRUITING

Hôpital Saint-Antoine

Paris, , France

Site Status RECRUITING

Hôpital de la Pitié-Salpêtrière

Paris, , France

Site Status RECRUITING

Hôpital Necker

Paris, , France

Site Status RECRUITING

CHU Bordeaux- Hôpital Haut Lévêque

Pessac, , France

Site Status RECRUITING

Centre Hospitalier de Périgueux

Périgueux, , France

Site Status RECRUITING

Centre Hospitalier de Saint-Quentin

Saint-Quentin, , France

Site Status RECRUITING

Debreceni Egyetem Klinikai Központ

Debrecen, , Hungary

Site Status RECRUITING

SzSzBM Korhazak es Egyetemi Oktatokorhaz

Nyíregyháza, , Hungary

Site Status RECRUITING

North Shore Hospital

Auckland, Auckland Province, New Zealand

Site Status RECRUITING

Palmerston North Hospital

Palmerston North, Manawatu, New Zealand

Site Status RECRUITING

Szpitale Pomorskie Sp. z o. o.

Gdynia, , Poland

Site Status RECRUITING

Wojewódzki Szpital Specjalistyczny w Legnicy

Legnica, , Poland

Site Status RECRUITING

SP ZOZ MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, , Poland

Site Status RECRUITING

Centrum Medyczne Pratia Poznań

Skórzewo, , Poland

Site Status RECRUITING

Narodowy Instytut Onkologii im. Marii, Skłodowskiej-Curie

Warsaw, , Poland

Site Status RECRUITING

Bucharest Oncology Institute "Prof.Dr.Al. Trestioreanu"

Bucharest, , Romania

Site Status RECRUITING

The Oncology Institute "Prof. Dr. Ion Chiricuţă" I.O.C.H.

Cluj-Napoca, , Romania

Site Status RECRUITING

University Clinical Center of Serbia

Belgrade, , Serbia

Site Status RECRUITING

Oncology Institute of Vojvodina

Kamenitz, , Serbia

Site Status RECRUITING

University Clinical Center Kragujevac

Kragujevac, , Serbia

Site Status RECRUITING

Clinical Hospital Center Zemun

Zemun, , Serbia

Site Status RECRUITING

Hospital Santa Creu i Sant Pau

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario de Burgos

Burgos, , Spain

Site Status RECRUITING

Hospital Universitario Virgen del Rocío

Seville, , Spain

Site Status RECRUITING

Countries

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

Facility Contacts

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Eric Lee, MD

Role: primary

714-698-0300

Haresh Jhangiani, MD

Role: backup

714-698-0300

Stacey Brown

Role: primary

404-780-7965

Melhem Solh, MD

Role: backup

404-255-1930

Jill Weisenbach

Role: primary

317-274-2848

Leta Ko

Role: primary

504-988-6120

Scott Degenhardt

Role: primary

402-691-5257

Doreen Padilla

Role: primary

505-913-8944

Denise Brigham

Role: primary

252-744-4924

Pam Shoup

Role: primary

419-214-4236

Diane Pershing

Role: primary

412-578-5987

Rich Wonder

Role: backup

412-578-4492

Barbara Miller

Role: primary

484-628-8549

Christine Hoare

Role: primary

+61 481 910 999

Connie Barlas, MD

Role: primary

+61 3 9516 2374

Liz Arnold

Role: primary

+61 3 9094 9516

Angela Bayley

Role: primary

+61 2 8890 7219

Jonathan Glum

Role: primary

306-655-1896

Geoffrey Edouart

Role: primary

01 48 95 75 05

Thomas Lelu

Role: primary

03 55 68 55 18

Nathalie Hugon

Role: primary

02 28 27 21 72

Dalila Wakrim

Role: primary

04 92 03 14 42

Anne Vekhoff, MD

Role: primary

01 49 28 34 29

Raouf Benchikh

Role: primary

01 84 82 70 31

Yohan Demay

Role: primary

01 44 49 46 57

Adélaïde Duperray

Role: backup

01 44 49 52 03

Souheyla Bouteman

Role: primary

05 57 65 60 18

Nathalie Franzl

Role: backup

05 57 62 33 23

Aude Jouinot

Role: primary

05 53 45 29 73

Abdelkrim Boulanouar

Role: primary

03 23 06 78 61

Gabriella Mezei, MD

Role: primary

+36 30 657 5238

Zsolt HORVÁTH

Role: primary

+36 20 998 5123

Sophie Leitch, MD

Role: primary

64 9 486 8900

RCTS Clinical Trials Unit

Role: primary

+64 6 350 8254

Karolina Cicha

Role: primary

+48 58 726 0380

Jadwiga Holodja, MD

Role: primary

505-149-579

Barbara Boruta-Pankowska

Role: backup

668-446-646

Jakub Zawadzki

Role: primary

+48 89-539-87-56

Marta Witowska

Role: backup

+48 89-539-87-56

Natalia Szymalak

Role: primary

512-491-461

Anna Pich

Role: primary

+ 48 22 546 2223

Monica Rosoiu, MD

Role: primary

+4078 3163 970

Nataliia Moskalenko

Role: primary

+4073 5888 501

Hanna Varytska

Role: backup

+4076 0818 421

Darko Antic, MD

Role: primary

+381 63 634 747

Nikica Sabljic

Role: backup

+381 61 192 46 68

Dijana Zekic

Role: primary

+381 64 08 00 868

Ana Dragovic

Role: primary

+381 65 325 97 65

Tamara Bibic

Role: primary

+381 60 511 10 45

Nuria Pérez

Role: primary

+34 93 291 90 00 ext. 8538

Raquel Alcaraz

Role: primary

+34 947281800 ext. 36078

Rocío Jiménez

Role: primary

+34 95 501 32 77

Other Identifiers

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KEYNOTE-C54

Identifier Type: OTHER

Identifier Source: secondary_id

P1605-SUR-D23

Identifier Type: -

Identifier Source: org_study_id

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