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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Diffuse Large B-Cell Lymphoma

Intervention / Treatment
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* Drug: Acalabrutinib
* Biological: Rituximab


Participation Criteria
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Eligibility Criteria
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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. Known to have tested positive for 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 > 6. History of or ongoing confirmed Progressive Multifocal Leukoencephalopathy. Known history of infection with HIV or any 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). Any concurrent anticancer treatment. 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.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acalabrutinib and Rituximab<br>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. | Drug: Acalabrutinib<br>* Patients will receive acalabrutinib orally with dosing schedule of X.<br>* Other names: CALQUENCE®;Biological: Rituximab<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with Grade 3 to 4 treatment emergent adverse events (TEAEs) |  | 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| Number of patients with adverse events |  | Screening (up to 28 days before day 1) Until Post-treatment follow-up (Up to 3.5 Years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemoimmunotherapy treatments, Treatment-naïve elderly patients