VAY736 in Combination With Ibrutinib in Patients With CLL on Ibrutinib

Chronic Lymphocytic Leukemia (CLL) Clinical Trial

Official title:

Phase Ib Open-label Study of VAY736 and Ibrutinib in Patients With Chronic Lymphocytic Leukemia (CLL) on Ibrutinib Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03400176
• Other study ID #: CVAY736Y2102
• Status: Terminated
• Phase: Phase 1
• Start date: April 9, 2018
• Est. completion date: September 29, 2023

Study information

• Verified date: November 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients enrolled to the study had chronic lymphocytic leukemia (CLL) and received ibrutinib. Patients have either received ibrutinib for one year without having had a complete response or patients developed a resistance mutation to ibrutinib. This study had two parts, a dose escalation part and a dose expansion part. Patients in the expansion part were enrolled into two arms depending on whether they had ibrutinib resistance mutations present at baseline.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 39
• Est. completion date: September 29, 2023
• Est. primary completion date: September 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of CLL per the WHO classification

• At least 18 years of age

• Lack of a complete response after receiving ibrutinib for > 1 year OR presence of known ibrutinib resistance mutation

• Actively receiving ibrutinib at either 420 mg (patients enrolled to the escalation arm) or at a stable dose for at least 2 months prior to starting study treatment (patients enrolled to the expansion arm)

Exclusion Criteria:

• Known history of HIV

• Active hepatitis B or C infection

• Receipt of attenuated vaccine within 2 weeks prior to starting study treatment.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia (CLL)
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• VAY736
Experimental
• ibrutinib
Approved medication

Locations

Country	Name	City	State
United States	Ohio State Comprehensive Cancer Center/James Cancer Hospital Ohio State University	Columbus	Ohio
United States	University of California San Diego - Moores Cancer Center	La Jolla	California
United States	David Geffen School of Medicine at UCLA David Geffen School of Med	Los Angeles	California
United States	Tennessee Oncology Centennial Medical Center	Nashville	Tennessee
United States	University of Utah / Huntsman Cancer Institute Oncology	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1 (Dose escalation only)	A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade = 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications that occurs within the first cycle of treatment during the dose escalation part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher. The duration of one treatment cycle is 28 days.	28 days
Primary	Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.	2 years
Primary	Incidence of dose reductions and dose interruptions of the combination of VAY736 and ibrutinib	Dose reductions and interruptions to assess the tolerability of the combination of VAY736 and ibrutinib.	2 years
Primary	Dose intensity of the combination of VAY736 and ibrutinib	Dose intensity is calculated as actual cumulative dose divided by duration of exposure.	2 years
Secondary	Rate of patients with complete response (CR) as assessed by investigators per IWCLL	Assessment of anti-tumor activity based on investigator assessment per International Working Group - Chronic Lymphocytic Leukemia (IWCLL)	Cycle 9 Day 1. The duration of one cycle is 28 days.
Secondary	Overall response rate (ORR) assessed by investigators per IWCLL criteria	ORR is defined as best overall response (BOR) of complete response (CR) or partial response (PR), assessed by investigators per IWCLL criteria.	2 years
Secondary	Time to progression (TTP)	TTP is the time from start of treatment to the date of event which is defined as the first documented progression or death due to underlying cancer.	2 years
Secondary	Clearance of ibrutinib resistance mutations (BTKC481 and/or PLC?2 hotspot)	Clearance of ibrutinib resistance mutation is defined as less than 1% mutation bearing alleles (BTKC481 and/or PLC?2) during treatment.; This endpoint is only applicable to the expansion arm involving chronic lymphocytic leukemia (CLL) patients on ibrutinib with acquired resistance mutations but without clinical relapse.	2 years
Secondary	Peak plasma concentration (Cmax) of VAY736 and ibrutinib	Plasma pharmacokinetic (PK) parameters calculated using non-compartmental methods.	2 years
Secondary	Area under the plasma concentration- time curve (AUC) of VAY736 and ibrutinib	Plasma pharmacokinetic (PK) parameters calculated using non-compartmental methods.	2 years
Secondary	Presence of anti-VAY736 antibodies	Number of participants with anti-VAY736 antibodies at baseline and on treatment.	Baseline, up to 2 years