Phase 2 Study of Disease Risk Mutation-Guided Finite Acalabrutinib+Venetoclax for Relapsed CLL Post-1L Finite cBTKi+BCL2i ± Obinutuzumab

Официальное название

The MAVRiC Study: A Phase II Study of Disease Risk Mutation Guided Finite Duration Acalabrutinib Plus Venetoclax for Relapse in CLL/SLL After First-line Finite Covalent BTKi Plus BCL2i Combination, With or Without Obinutuzumab

Обзор

This study will evaluate the efficacy and safety of finite-duration acalabrutinib plus venetoclax therapy in patients with relapsed CLL or SLL, and have previously responded to first line (1L) cBTKi + BCL2i therapy (± obinutuzumab) and maintained a response for at least two years post-treatment.

Подробное описание

The purpose of this study is to explore the use of second line (2L) treatment with AV after relapse following first line (1L) cBTKi + BCL2i by assessment of ORR in participants with CLL/SLL. This study will generate efficacy and safety data needed to understand outcomes associated with AV in patients who initially responded with partial remission (PR) or better for a minimum of 2 years from the end of 1L cBTKi + BCL2i combination treatment and are experiencing clinical relapse requiring further treatment. MAVRiC explores AV as second-line (2L) CLL/SLL treatment after relapse on first-line (1L) cBTKi + BCL-2 by assessment of overall response rate (ORR)

* The study duration for each participant will be up to 5 year. * The study consists of screening, treatment, and post-intervention follow-up periods. * Participants will be grouped into low or high risk cohorts based on disease risk determined by IGHV mutation and TP53 aberrancy.

Вмешательства

• Препарат Acalabrutinib
  Acalabrutinib is an orally available cBTKi that inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway.
• Препарат Venetoclax
  Venetoclax is an orally bioavailable inhibitor of the anti-apoptotic protein BCL-2

Первичные конечные точки

• Overall Response Rate (ORR) [Срок оценки: ORR assessed at multiple timepoints during treatment period (each cycle is 28 days). Timepoint for primary analysis is at completion of cycle 14]

Вторичные конечные точки (7)

• Progression Free Survival (PFS) [Срок оценки: PFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)]
• Duration of Response (DoR) [Срок оценки: DoR will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)]
• Event Free Survival (EFS) [Срок оценки: EFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)]
• Time to Next Treatment (TTNT) [Срок оценки: TTNT will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)]
• Overall Survival (OS) [Срок оценки: OS will be assessed every 3 months through the study completion, for 5 years]
• Rate of undetectable Minimal Residual Disease (uMRD) [Срок оценки: uMRD will be measured at 3 months after last treatment]
• Treatment-Emergent Adverse Events (safety and tolerability) of second-line (2L) treatment with Acalabrutinib and Venetoclax after relapse following 1L cBTKi + BCL2i [Срок оценки: Safety and tolerability will be evaluated throughout the study for 5 years]

Критерии участия

Main Inclusion Criteria:

• Participant must be ≥ 18 years at the time of signing informed consent.
• Diagnosis of CLL/SLL according to iwCLL guidelines 2018 (Hallek et al. 2018)
• Participants must have received first line treatment with fixed duration covalent BTKi plus BCL2i therapy (± obinutuzumab) with a response ≥ PR (i.e., CR, CRi, nPR, or PR) with a minimum of 2 years since the end of the prior 1L treatment.
• The following data must be available or at least the appropriate samples drawn/acquired prior to dosing:

• IGHV (mutated vs. unmutated)
• del(17p) (present or absent)
• TP53 mutation (present or absent)
• ECOG performance status 0, 1 or 2
• Adequate organ and bone marrow (BM) function.

Main Exclusion Criteria:

• Any evidence of diseases that, in the investigator's opinion, makes it undesirable for patient to participate in the study.
• Significant cardiovascular or cerebrovascular disease.
• Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease).
• Child-Pugh B/C liver cirrhosis.
• History of prior or current malignancy.
• HIV positive
• History of progressive multifocal leukoencephalopathy (PML).
• Active hepatitis B or C infection:
• Corticosteroid use > 20 mg within 1 week before the first dose of study intervention.
• History of hypersensitivity or anaphylaxis to study intervention(s).
• Requires treatment with a strong CYP3A4 inhibitor/inducer.
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
• Major surgical procedure within 30 days of the first dose of study intervention.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Италия · 7 центров

• Research Site — Meldola
• Research Site — Milan
• Research Site — Milan
• Research Site — Padua
• Research Site — Ravenna
• Research Site — Rome
• Research Site — Torino

Испания · 7 центров

• Research Site — Barcelona
• Research Site — Barcelona
• Research Site — Granada
• Research Site — Madrid
• Research Site — Madrid
• Research Site — Madrid
• Research Site — Majadahonda

Польша · 6 центров

• Research Site — Bydgoszcz
• Research Site — Krakow
• Research Site — Lodz
• Research Site — Lublin
• Research Site — Warsaw
• Research Site — Warsaw

США · 5 центров

• Research Site — Boston
• Research Site — Charlotte
• Research Site — Charlotte
• Research Site — Durham
• Research Site — Winston-Salem

Бразилия · 5 центров

• Research Site — Goiânia
• Research Site — Porto Alegre
• Research Site — Porto Alegre
• Research Site — São Paulo
• Research Site — São Paulo

Чехия · 3 центра

• Research Site — Brno
• Research Site — Hradec Kralova
• Research Site — Ostrava

Ирландия · 2 центра

• Research Site — Dublin
• Research Site — Dublin

Австрия · 1 центр

• Research Site — Horn

Идентификаторы

NCT: NCT07024706 · D8220C00036

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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