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
- Phase
- Phase 2
- Intervention
- Acalabrutinib
- Conditions
- Diffuse Large B-Cell Lymphoma
- Sponsor
- AstraZeneca
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Percentage of patients with Grade 3 to 4 treatment emergent adverse events (TEAEs)
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
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.
Investigators
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 \>
- •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).
Arms & Interventions
Acalabrutinib and Rituximab
Patients will receive Dose A of acalabrutinib orally in X dosing schedule beginning on Cycle 1 Day 1 for a maximum of 28 cycles or until 2014 Lugano Classification for Non-Hodgkin's Lymphoma (NHL)-defined disease progression or another discontinuation criterion is met. Patients will also receive an intravenous (IV) infusion of Dose B rituximab on Cycle 1 Day 15 and Dose C of rituximab as an subcutaneous (SC) injection on Day 1 of Cycle 2 through Cycle 8.
Intervention: Acalabrutinib
Acalabrutinib and Rituximab
Patients will receive Dose A of acalabrutinib orally in X dosing schedule beginning on Cycle 1 Day 1 for a maximum of 28 cycles or until 2014 Lugano Classification for Non-Hodgkin's Lymphoma (NHL)-defined disease progression or another discontinuation criterion is met. Patients will also receive an intravenous (IV) infusion of Dose B rituximab on Cycle 1 Day 15 and Dose C of rituximab as an subcutaneous (SC) injection on Day 1 of Cycle 2 through Cycle 8.
Intervention: Rituximab
Outcomes
Primary Outcomes
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 Outcomes
- Progression free survival (PFS)(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))
- Number of patients with adverse events(Screening (up to 28 days before day 1) Until Post-treatment follow-up (Up to 3.5 Years))
- Objective response rate (ORR)(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))
- Duration of response (DoR)(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)(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)(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))
- Change from baseline in Timed Up and Go test (TUG)(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))