Clinical trial NCT05952024: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Keywords: Chemoimmunotherapy treatments
Treatment-naïve elderly patients
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-07-19
Enrollment: 80
Sex: ALL
Minimum age (years): 65
Maximum age (years): 99
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of patients with Grade 3 to 4 treatment emergent adverse events (TEAEs)
timeFrame: 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:
measure: Objective response rate (ORR)
timeFrame: 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)
measure: Progression free survival (PFS)
timeFrame: 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)
measure: Event-Free Survival (EFS)
timeFrame: 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)
measure: Overall survival (OS)
timeFrame: 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)
measure: Duration of response (DoR)
timeFrame: 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)
measure: Change from baseline in Timed Up and Go test (TUG)
timeFrame: 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)
measure: Number of patients with adverse events
timeFrame: Screening (up to 28 days before day 1) Until Post-treatment follow-up (Up to 3.5 Years)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Stamford
country: United States
facility: Research Site
state: Connecticut
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Des Moines
country: United States
facility: Research Site
state: Iowa
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Beltsville
country: United States
facility: Research Site
state: Maryland
city: Towson
country: United States
facility: Research Site
state: Maryland
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Sioux Falls
country: United States
facility: Research Site
state: South Dakota
city: Lubbock
country: United States
facility: Research Site
state: Texas
city: Olympia
country: United States
facility: Research Site
state: Washington
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Barretos
country: Brazil
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Brasilia
country: Brazil
facility: Research Site
city: Brasilia
country: Brazil
facility: Research Site
city: Brasilia
country: Brazil
facility: Research Site
city: Campinas
country: Brazil
facility: Research Site
city: Curitiba
country: Brazil
facility: Research Site
city: Florianópolis
country: Brazil
facility: Research Site
city: Florianópolis
country: Brazil
facility: Research Site
city: Goiania
country: Brazil
facility: Research Site
city: Natal
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Recife
country: Brazil
facility: Research Site
city: Ribeirão Preto
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: Sao Luis
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sorocaba
country: Brazil
facility: Research Site
city: São José do Rio Preto
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Gyeongsangnam-do
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Jeonju-si
country: Korea, Republic of
facility: Research Site
city: Seo-gu
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Ulsan
country: Korea, Republic of
facility: Research Site
city: San Juan
country: Puerto Rico
facility: Research Site
Study officials:
References: