Phase 2 Study of Disease Risk Mutation-Guided Finite Acalabrutinib+Venetoclax for Relapsed CLL Post-1L Finite cBTKi+BCL2i ± Obinutuzumab

ConditionsChronic Lymphocytic Leukemia (CLL)Small Lymphocytic Lymphoma (SLL)

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18-130

SponsorAstraZeneca

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participant must be ≥ 18 years at the time of signing informed consent.

Diagnosis of CLL/SLL according to iwCLL guidelines 2018 (Hallek et al. 2018)

Participants must have received first line treatment with fixed duration covalent BTKi plus BCL2i therapy (± obinutuzumab) with a response ≥ PR (i.e., CR, CRi, nPR, or PR) with a minimum of 2 years since the end of the prior 1L treatment.

IGHV (mutated vs. unmutated)

Disqualifiers

Any evidence of diseases that, in the investigator's opinion, makes it undesirable for patient to participate in the study.

Significant cardiovascular or cerebrovascular disease.

Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease).

Child-Pugh B/C liver cirrhosis.

Trial design

Design model

Single group

Treatments tested in this trial

Acalabrutinib
Drug
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
Drug
Venetoclax is an orally bioavailable inhibitor of the anti-apoptotic protein BCL-2

Treatment groups

80 Participants

are divided into 1 treatment group

Group A: Acalabrutinib and VenetoclaxExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

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

Secondary outcomes

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)