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Acalabrutinib for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

ConditionChronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorSeema Bhat

About this trial

This phase II trial tests how well acalabrutinib works in treating patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and evaluates how treatment with acalabrutinib affects heart function. Acalabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers at abnormal levels. This may help keep cancer cells from growing and spreading. CLL/SLL patients treated with a different BTK inhibitor called ibrutinib often experience cardiac side effects, leading to discontinuation of life-saving therapy. Treatment with acalabrutinib after discontinuing, or even before starting, treatment with ibrutinib may reverse or prevent cardiac side effects and be an effective treatment option for patients with CLL/SLL.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Men and women >= 18 years of age

Diagnosis of CLL/SLL meeting criteria as defined by International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2018 criteria

CLL patients cardiac intolerant to current treatment with ibrutinib as defined by AF or other cardiac arrhythmias. Other ibrutinib-related intolerances will be excluded

Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

Disqualifiers

Prior exposure to acalabrutinib for primary cohort and prior exposure to BTK inhibitor for pilot cohort

Presence of C481S mutation or PCLG2 mutation

Disease progression on ibrutinib

Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or carcinoma in situ of the prostate at any time prior to study

Trial design

Design model

Single group

Treatments tested in this trial

  • Acalabrutinib

    Drug

    Given PO

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood samples

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow aspiration

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Magnetic Resonance Imaging of the Heart

    Procedure/Surgery

    Undergo CMR

Treatment groups

61 Participants
are divided into 1 treatment group
Group A: Treatment (acalabrutinib)Experimental treatment 6 interventions

Trial outcomes

Primary outcomes

1

Cardiac magnetic resonance imaging changes

The cardiac MRI changes that will be assessed include Extracellular volume (ECV), Native T1, and T2, where changes in ECV from baseline to 3-month post acalabrutinib initiation would be the primary endpoint

Time frame
Baseline to 3-month post acalabrutinib initiation

Secondary outcomes

1

Overall response rate (ORR)

ORR will be defined as the number of patients with a response (complete response \[CR\], partial response \[PR\], PR with lymphocytosis) divided by the number of eligible patients who start study treatment. Response rates including CR and ORR will be estimated at the end of treatment and at various time points with exact 95% confidence intervals. The change in response over time will be presented in a descriptive manner as well as graphically through use of a Sankey plot.

Time frame
At the end of cycle 24 (1 cycle = 28 days)
2

Clinical progression free survival (PFS)

PFS will be described using the method of Kaplan-Meier and estimates at 3 years will be provided with 95% confidence intervals.

Time frame
From start of study treatment until first progression or death, assessed at 3 years
3

C481S/PLCG2 mutation free survival

Mutation free survival will be described using the method of Kaplan-Meier and estimates at 3 years will be provided with 95% confidence intervals.

Time frame
At 3 years
4

Incidence of recurrence of grade 2 or greater adverse events (AEs) that previously led to ibrutinib intolerance

The recurrence rate will be calculated as the number of patients who have recurrence (grade 2 or higher) of the AE that previously led to ibrutinib intolerance during the first 12 cycles of single agent acalabrutinib therapy divided by the number of eligible patients who start acalabrutinib therapy. The rate of recurrence of grade 2 or greater AEs will be analyzed using an exact binomial test for a single proportion and will be estimated with exact 95% confidence intervals.

Time frame
During the first 12 cycles of single agent acalabrutinib (1 cycle = 28 days)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Seema Bhat

Lead sponsor

Ohio State University Comprehensive Cancer Center

Sponsor institution

Acerta Pharma, LLC

Collaborator

AstraZeneca

Collaborator

Source ClinicalTrials.gov
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