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

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Objective response rate (ORR) in each of the study arms [Срок оценки: Approximately 24 months]

Вторичные конечные точки (8)

• Rate of Adverse Events using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 in each of the study arms [Срок оценки: Approximately 24 months]
• Duration of response (DOR) in each of the study arms [Срок оценки: Approximately 24 months]
• Time to response in each of the study arms [Срок оценки: Approximately 24 months]
• Progression-Free Survival in each of the study arms [Срок оценки: Approximately 48 months]
• Disease control rate (DCR) in each of the study arms [Срок оценки: Approximately 24 months]
• Complete response (CR) rate in each of the study arms [Срок оценки: Approximately 24 months]
• Changes in Patient Reported Outcomes using the FACT-Lym Assessment [Срок оценки: Approximately 24 months]
• Changes in Patient Reported Outcomes using the EQ-5D-5L Assessment [Срок оценки: Approximately 24 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 17 центров

• Compassionate Cancer Care Medical Group — Fountain Valley
• Boca Raton Regional Hospital — Boca Raton
• BRCR Medical Center Inc. — Hollywood
• BRCR Medical Center Inc. — Plantation
• Comprehensive Hematology and Oncology — St. Petersburg
• Blood and Marrow Transplant Group of Georgia — Atlanta
• Indiana University Health Melvin and Bren Simon Cancer Center — Indianapolis
• Tulane Cancer Center Office of Clinical Research — New Orleans
• … и ещё 9 центров

Франция · 10 центров

• Hôpital Avicenne — Bobigny
• Centre d'Oncologie de Gentilly — Nancy
• Hôpital Privé du Confluent — Nantes
• Centre Antoine Lacassagne — Nice
• Hôpital Saint-Antoine — Paris
• Hôpital de la Pitié-Salpêtrière — Paris
• Hôpital Necker — Paris
• CHU Bordeaux- Hôpital Haut Lévêque — Pessac
• … и ещё 2 центра

Польша · 5 центров

• Szpitale Pomorskie Sp. z o. o. — Gdynia
• Wojewódzki Szpital Specjalistyczny w Legnicy — Legnica
• SP ZOZ MSWiA z Warmińsko-Mazurskim Centrum Onkologii w Olsztynie — Olsztyn
• Centrum Medyczne Pratia Poznań — Skórzewo
• Narodowy Instytut Onkologii im. Marii, Skłodowskiej-Curie — Warsaw

Австралия · 4 центра

• Royal Adelaide Hospital — Adelaide
• Epworth Freemasons Hospital — Melbourne
• Box Hill Hospital — Melbourne
• Westmead Hospital — Westmead

Сербия · 4 центра

• University Clinical Center of Serbia — Belgrade
• Oncology Institute of Vojvodina — Kamenitz
• University Clinical Center Kragujevac — Kragujevac
• Clinical Hospital Center Zemun — Zemun

Испания · 3 центра

• Hospital Santa Creu i Sant Pau — Barcelona
• Hospital Universitario de Burgos — Burgos
• Hospital Universitario Virgen del Rocío — Seville

Венгрия · 2 центра

• Debreceni Egyetem Klinikai Központ — Debrecen
• SzSzBM Korhazak es Egyetemi Oktatokorhaz — Nyíregyháza

Новая Зеландия · 2 центра

• North Shore Hospital — Auckland
• Palmerston North Hospital — Palmerston North

Румыния · 2 центра

• Bucharest Oncology Institute "Prof.Dr.Al. Trestioreanu" — Bucharest
• The Oncology Institute "Prof. Dr. Ion Chiricuţă" I.O.C.H. — Cluj-Napoca

Канада · 1 центр

• Saskatoon Cancer Center — Saskatoon

Идентификаторы

NCT: NCT04920617 · P1605-SUR-D23 · KEYNOTE-C54

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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