Pirtobrutinib (LOXO-305) and Venetoclax for the Treatment of Patients With CLL or SLL Resistant to Covalent BTKi
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorKerry Rogers
About this trial
This phase II trial tests how well pirtobrutinib (LOXO-305) and venetoclax works in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that remains despite treatment (resistant) with covalent bruton tyrosine kinase inhibitors (BTKi). Pirtobrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the a protein that signals cancer cells to multiply. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Giving pirtobrutinib and venetoclax may kill more cancer cells in patients with CLL or SLL that is resistant to covalent BTKi.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of CLL or SLL according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines
Detectable CLL on flow cytometry of the blood or marrow at time of enrollment
Age ≥ 18 years old
Eastern Cooperative Oncology Group (ECOG) performance 0-2
Disqualifiers
Inability to tolerate 2 Liters of oral or intravenous (IV) hydration
Prior venetoclax exposure > 13 months or known resistance to venetoclax
Known hypersensitivity to any of the excipients of pirtobrutinib or venetoclax
Need for treatment with warfarin or other vitamin K antagonist during study treatment
Trial design
Design model
Single group
Treatments tested in this trial
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration and biopsy
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow aspiration and biopsy
Computed Tomography
Procedure/SurgeryUndergo CT
Pirtobrutinib
DrugGiven PO
Venetoclax
DrugGiven PO
Treatment groups
30 Participants
are divided into 1 treatment groupGroup A: Treatment (pirtobrutinib, venetoclax)Experimental treatment 6 interventions
Trial outcomes
Primary outcomes
1
Rate of undetectable minimal residual disease (uMRD)
The rate of uMRD will be defined as the percentage of patients who have uMRD in both the peripheral blood and bone marrow at C21D1.
Time frame
At cycle 21 day 1 (C21D1) [each cycle lasts 28 days]Secondary outcomes
1
Best overall response rate (ORR)
Best ORR will be estimated with exact 95% confidence intervals.
Time frame
At cycle 21 day 1 (C21D1) [each cycle lasts 28 days]2
Overall Response Rate (ORR)
ORR will be estimated with exact 95% confidence intervals.
Time frame
At cycle 21 day 1 (C21D1) [each cycle lasts 28 days]3
Progression-free survival (PFS) for all patients
Clinical disease progression will be assessed by International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria. PFS will be described using the method of Kaplan-Meier. Median and/or estimates at clinically meaningful time points for PFS will be reported with 95% confidence intervals.
Time frame
At start of treatment to progression or death up to 18 months after completion of study treatment4
PFS in patients who achieve uMRD and those who do not achieve uMRD with pirtobrutinib and venetoclax
Clinical disease progression will be assessed by iwCLL 2018 criteria. PFS will be described using the method of Kaplan-Meier. Median and/or estimates at clinically meaningful time points for PFS will be reported with 95% confidence intervals.
Time frame
At end of treatment to progression or death up to 18 months after completion of study treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Kerry Rogers
Lead sponsor
Ohio State University Comprehensive Cancer Center
Sponsor institution
Source ClinicalTrials.gov