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

Diffuse Large B-Cell Lymphoma Clinical Trial

— ACRUE  

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05952024
• Other study ID #: D8227C00002
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 29, 2024
• Est. completion date: September 29, 2027

Study information

• Verified date: November 2023
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: September 29, 2027
• Est. primary completion date: September 29, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Number of patients with adverse events		Screening (up to 28 days before day 1) Until Post-treatment follow-up (Up to 3.5 Years)