This study will evaluate the efficacy and safety of finite-duration acalabrutinib plus venetoclax therapy in patients with relapsed CLL or SLL, and have previously responded to first line (1L) cBTKi + BCL2i therapy (± obinutuzumab) and maintained a response for at least two years post-treatment.
The purpose of this study is to explore the use of second line (2L) treatment with AV after relapse following first line (1L) cBTKi + BCL2i by assessment of ORR in participants with CLL/SLL. This study will generate efficacy and safety data needed to understand outcomes associated with AV in patients who initially responded with partial remission (PR) or better for a minimum of 2 years from the end of 1L cBTKi + BCL2i combination treatment and are experiencing clinical relapse requiring further treatment. MAVRiC explores AV as second-line (2L) CLL/SLL treatment after relapse on first-line (1L) cBTKi + BCL-2 by assessment of overall response rate (ORR) * The study duration for each participant will be up to 5 year. * The study consists of screening, treatment, and post-intervention follow-up periods. * Participants will be grouped into low or high risk cohorts based on disease risk determined by IGHV mutation and TP53 aberrancy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Acalabrutinib is an orally available cBTKi that inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway.
Venetoclax is an orally bioavailable inhibitor of the anti-apoptotic protein BCL-2
Overall Response Rate (ORR)
ORR, defined as the proportion of participants who achieve best response of CR, CRi, nPR, or PR per iwCLL criteria as assessed by the investigator.
Time frame: ORR assessed at multiple timepoints during treatment period (each cycle is 28 days). Timepoint for primary analysis is at completion of cycle 14
Progression Free Survival (PFS)
PFS is defined as time from date of the first dose until progression per iwCLL criteria or death due to any cause in the absence of progression.
Time frame: PFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)
Duration of Response (DoR)
DoR is defined as the time from the date of first documented response until date of documented progression per iwCLL criteria or death due to any cause.
Time frame: DoR will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)
Event Free Survival (EFS)
EFS is defined as the time from date of the first dose until the first occurrence of disease progression, initiation of subsequent CLL/SLL therapy, or death due to any cause.
Time frame: EFS will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)
Time to Next Treatment (TTNT)
TTNT is defined as the time from date of the first dose to the initiation of subsequent CLL/SLL therapy or death due to any cause
Time frame: TTNT will be assessed from Cycle 3 to Cycle 24 during treatment period (each cycle is 28 days)
Overall Survival (OS)
OS is defined as the time from date of the first dose until the date of death due to any cause.
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Research Site
Boston, Massachusetts, United States
RECRUITINGResearch Site
Charlotte, North Carolina, United States
WITHDRAWNResearch Site
Charlotte, North Carolina, United States
RECRUITINGResearch Site
Durham, North Carolina, United States
RECRUITINGResearch Site
Winston-Salem, North Carolina, United States
RECRUITINGResearch Site
Horn, Austria
RECRUITINGResearch Site
Goiânia, Brazil
NOT_YET_RECRUITINGResearch Site
Porto Alegre, Brazil
NOT_YET_RECRUITINGResearch Site
Porto Alegre, Brazil
NOT_YET_RECRUITINGResearch Site
São Paulo, Brazil
NOT_YET_RECRUITING...and 26 more locations
Time frame: OS will be assessed every 3 months through the study completion, for 5 years
Rate of undetectable Minimal Residual Disease (uMRD)
Rate of peripheral blood (PB) uMRD, defined as proportion of participants achieving remission based on a clonoSEQ® assay result of \<1 CLL cell per 100,000 leukocytes (\< 10-5).
Time frame: uMRD will be measured at 3 months after last treatment
Treatment-Emergent Adverse Events (safety and tolerability) of second-line (2L) treatment with Acalabrutinib and Venetoclax after relapse following 1L cBTKi + BCL2i
Safety and tolerability will be evaluated in terms of AEs/SAEs, AEs leading to treatment discontinuation and deaths, and relevant clinical laboratory results.
Time frame: Safety and tolerability will be evaluated throughout the study for 5 years