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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B-Cell Lymphoma
• Intervention / Treatment: Drug: Acalabrutinib; Biological: Rituximab

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Brazil
  • Barretos, Brazil, 14784-400
    • Active, not recruiting
    • Research Site
  • Belo Horizonte, Brazil, 30150-221
    • Active, not recruiting
    • Research Site
  • Brasília, Brazil, 70390-700
    • Recruiting
    • Research Site
  • Brasília, Brazil, 70200-730
    • Active, not recruiting
    • Research Site
  • Brasília, Brazil, 70840-901
    • Active, not recruiting
    • Research Site
  • Campinas, Brazil, 13060-803
    • Active, not recruiting
    • Research Site
  • Curitiba, Brazil, 81520-060
    • Active, not recruiting
    • Research Site
  • Florianópolis, Brazil, 88034-000
    • Recruiting
    • Research Site
  • Florianópolis, Brazil, 88020-210
    • Active, not recruiting
    • Research Site
  • Goiânia, Brazil, 74605-020
    • Active, not recruiting
    • Research Site
  • Natal, Brazil, 59075-740
    • Active, not recruiting
    • Research Site
  • Porto Alegre, Brazil, 90035-003
    • Active, not recruiting
    • Research Site
  • Porto Alegre, Brazil, 90880-480
    • Active, not recruiting
    • Research Site
  • Recife, Brazil, 50070-480
    • Active, not recruiting
    • Research Site
  • Ribeirão Preto, Brazil, 14048-900
    • Active, not recruiting
    • Research Site
  • Rio de Janeiro, Brazil, 20231-050
    • Active, not recruiting
    • Research Site
  • Sorocaba, Brazil, 18030-005
    • Active, not recruiting
    • Research Site
  • São José do Rio Preto, Brazil, 15090-000
    • Active, not recruiting
    • Research Site
  • São Luís, Brazil, 65060-645
    • Active, not recruiting
    • Research Site
  • São Paulo, Brazil, 01229-010
    • Active, not recruiting
    • Research Site
  • São Paulo, Brazil, 01409-02
    • Active, not recruiting
    • Research Site
  • São Paulo, Brazil, 05652-900
    • Active, not recruiting
    • Research Site
  • São Paulo, Brazil, 08270-070
    • Completed
    • Research Site
  • São Paulo, Brazil, 1323000
    • Active, not recruiting
    • Research Site
• Puerto Rico
  • San Juan, Puerto Rico, 00917
    • Active, not recruiting
    • Research Site
• South Korea
  • Busan, South Korea, 47392
    • Recruiting
    • Research Site
  • Busan, South Korea, 49241
    • Active, not recruiting
    • Research Site
  • Daegu, South Korea, 42601
    • Active, not recruiting
    • Research Site
  • Gyeongsangnam-do, South Korea, 52727
    • Active, not recruiting
    • Research Site
  • Incheon, South Korea, 405-760
    • Active, not recruiting
    • Research Site
  • Jeonju, South Korea, 54907
    • Active, not recruiting
    • Research Site
  • Seogu, South Korea, 49201
    • Active, not recruiting
    • Research Site
  • Seoul, South Korea, 06591
    • Recruiting
    • Research Site
  • Seoul, South Korea, 03722
    • Active, not recruiting
    • Research Site
  • Seoul, South Korea, 06351
    • Active, not recruiting
    • Research Site
  • Seoul, South Korea, 05505
    • Active, not recruiting
    • Research Site
  • Seoul, South Korea, 07985
    • Active, not recruiting
    • Research Site
  • Suwon, South Korea, 16499
    • Active, not recruiting
    • Research Site
  • Ulsan, South Korea, 44033
    • Active, not recruiting
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Withdrawn
    • Research Site
  • Kaohsiung City, Taiwan, 833
    • Withdrawn
    • Research Site
  • Tainan, Taiwan, 736
    • Withdrawn
    • Research Site
  • Taipei, Taiwan, 100
    • Withdrawn
    • Research Site
• United States
  • California
    • Berkeley, California, United States, 94704
      • Withdrawn
      • Research Site
    • La Jolla, California, United States, 92093
      • Completed
      • Research Site
    • Orange, California, United States, 92868
      • Recruiting
      • Research Site
  • Connecticut
    • Stamford, Connecticut, United States, 06902
      • Withdrawn
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Active, not recruiting
      • Research Site
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Recruiting
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Withdrawn
      • Research Site
  • Maryland
    • Beltsville, Maryland, United States, 20705
      • Active, not recruiting
      • Research Site
    • Towson, Maryland, United States, 21204
      • Active, not recruiting
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Active, not recruiting
      • Research Site
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Withdrawn
      • Research Site
  • Texas
    • Lubbock, Texas, United States, 79410
      • Active, not recruiting
      • Research Site
  • Washington
    • Olympia, Washington, United States, 98506
      • Active, not recruiting
      • Research Site
    • Tacoma, Washington, United States, 98405
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Acalabrutinib; Patients will receive acalabrutinib orally with dosing schedule of X.; Other Names: CALQUENCE®; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2024
• Primary Completion (Estimated): April 22, 2029
• Study Completion (Estimated): April 22, 2029

Study Registration Dates

• First Submitted: July 11, 2023
• First Submitted That Met QC Criteria: July 11, 2023
• First Posted (Actual): July 19, 2023

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Chemoimmunotherapy treatments; Treatment-naïve elderly patients
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Rituximab; acalabrutinib
• Other Study ID Numbers: D8227C00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No