Study of Acalabrutinib and Rituximab in Untreated Elderly and/or Frail Patients With DLBCL

Official title

A Prospective, Open-Label, Single-Arm, Phase II Study of Acalabrutinib and Rituximab in Untreated Elderly and/or Frail Patients With Diffuse Large B-Cell Lymphoma (ACRUE)

Overview

The study will measure the safety, tolerability, and efficacy with acalabrutinib in combination with rituximab in treatment-naïve elderly and/or frail patients with diffuse large B-cell lymphoma (DLBCL), who are otherwise unsuitable for standard front line chemoimmunotherapy treatments.

Detailed description

Treatment-naïve elderly and/or frail patients with DLBCL will be treated with acalabrutinib in combination with rituximab in a single arm.

Study details include the following:

* The study duration will be up to 108 weeks for each patient, including up to 28 days for screening and 104 weeks of treatment and follow-up. * The treatment duration will be up to 8 cycles for rituximab and 28 cycles for acalabrutinib both beginning at cycle 1.

Interventions

• Drug Acalabrutinib
  Patients will receive acalabrutinib orally with dosing schedule of X.
• Biological Rituximab
  Patients will receive rituximab via IV infusion on Cycle 1 Day 15 and via SC injection on Day 1 of Cycle 2 through Cycle 8.

Primary outcome measures

• Percentage of patients with Grade 3 to 4 treatment emergent adverse events (TEAEs) [Time frame: Cycle 1 Day 1 (Cycles 1 to 8 is 21 days and Cycles 9 to 28 is 28 days) through End of treatment EoT [30 days of discontinuation] (Up to 3.5 Years)]

Secondary outcome measures (7)

• Objective response rate (ORR) [Time frame: Cycle 1 Day 1 (Cycles 1 to 8 is 21 days and Cycles 9 to 28 is 28 days) Until disease progression or last evaluable assessment in the absence of progression (Up to 3.5 Years)]
• Progression free survival (PFS) [Time frame: Cycle 1 Day 1 (Cycles 1 to 8 is 21 days and Cycles 9 to 28 is 28 days) Until disease progression or last evaluable assessment in the absence of progression (Up to 3.5 Years)]
• Event-Free Survival (EFS) [Time frame: Cycle 1 Day 1 (Cycles 1 to 8 is 21 days and Cycles 9 to 28 is 28 days) Until disease progression or last evaluable assessment in the absence of progression (Up to 3.5 Years)]
• Overall survival (OS) [Time frame: Cycle 1 Day 1 (Cycles 1 to 8 is 21 days and Cycles 9 to 28 is 28 days) Until Post-treatment follow-up (Up to 3.5 Years)]
• Duration of response (DoR) [Time frame: Cycle 1 Day 1 (Cycles 1 to 8 is 21 days and Cycles 9 to 28 is 28 days) Until disease progression or last evaluable assessment in the absence of progression (Up to 3.5 Years)]
• Change from baseline in Timed Up and Go test (TUG) [Time frame: Cycle 1 Day 1 (Cycles 1 to 8 is 21 days and Cycles 9 to 28 is 28 days) Until Post-treatment follow-up (Up to 3.5 Years)]
• Number of patients with adverse events [Time frame: Screening (up to 28 days before day 1) Until Post-treatment follow-up (Up to 3.5 Years)]

Eligibility criteria

Inclusion criteria

• ≥ 80 years of age at the time of screening, or
• ≥ 65 to 79 years of age at the time of screening and considered ineligible for chemoimmunotherapy
• Histologically documented DLBCL
• No prior treatment for DLBCL
• Stage II, III, or IV disease by the Ann Arbor Classification .
• Eastern Cooperative Oncology Group performance status of 0, 1, or 2 with no deterioration over the previous 2 weeks prior to baseline or day of the first dosing except when due to underlying lymphoma.
• At least 1 lesion that can be accurately measured at baseline as ≥ 10 mm in the longest diameter with computed tomography or magnetic resonance imaging and is suitable for accurate repeated measurements.
• Adequate organ and marrow function independent of growth factor or transfusion support within 1 week of Screening.

Exclusion criteria

• Any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant, and active bleeding diseases), that would make the study undesirable for the patient or that would impact compliance with the protocol.
• History of prior or current malignancy, that would affect compliance with the protocol or interpretation of the results.
• Serologic status reflecting active hepatitis B or C infection.
• Serological positivity or known infection with HIV.
• Active central nervous system involvement by lymphoma, leptomeningeal disease, or spinal cord compression.
• Any comorbidity or organ system impairment rated with a single Cumulative Illness Rating Scale-Geriatric score (CIRS-G) of 4 or a total CIRS-G score of > 17.
• History of or ongoing confirmed Progressive Multifocal Leukoencephalopathy.
• Known active significant infection.
• History of stroke or intracranial haemorrhage within 6 months before the first dose of study drug.
• History of bleeding diathesis (eg, haemophilia, von Willebrand disease).
• Major surgical procedure within 30 days of first dose of study intervention or anticipated major surgery during the study timeframe.
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
• Received a live virus vaccination within 28 days of the first dose of study drug.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Brazil · 24 centers

• Research Site — Barretos
• Research Site — Belo Horizonte
• Research Site — Brasília
• Research Site — Brasília
• Research Site — Brasília
• Research Site — Campinas
• Research Site — Curitiba
• Research Site — Florianópolis
• … and 16 more centers

United States · 14 centers

• Research Site — Berkeley
• Research Site — La Jolla
• Research Site — Orange
• Research Site — Stamford
• Research Site — Jacksonville
• Research Site — Des Moines
• Research Site — Lexington
• Research Site — Beltsville
• … and 6 more centers

South Korea · 14 centers

• Research Site — Busan
• Research Site — Busan
• Research Site — Daegu
• Research Site — Gyeongsangnam-do
• Research Site — Incheon
• Research Site — Jeonju
• Research Site — Seogu
• Research Site — Seoul
• … and 6 more centers

Taiwan · 4 centers

• Research Site — Kaohsiung City
• Research Site — Kaohsiung City
• Research Site — Tainan
• Research Site — Taipei

Puerto Rico · 1 center

• Research Site — San Juan

Identifiers

NCT: NCT05952024 · D8227C00002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗