Clinical trial NCT03400176: VAY736 in Combination With Ibrutinib in Patients With CLL on Ibrutinib
Official title: Phase Ib Open-label Study of VAY736 and Ibrutinib in Patients With Chronic Lymphocytic Leukemia (CLL) on Ibrutinib Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Lymphocytic Leukemia (CLL)
Keywords: Ibrutinib
VAY736
Chronic lymphocytic leukemia
CLL
Bruton's Tyrosine Kinase
BTK mutation
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-01-17
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Patients enrolled to the study had chronic lymphocytic leukemia (CLL) and received ibrutinib. Patients had 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLTs) in Cycle 1 (Escalation Only)
timeFrame: 28 days
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of study treatment up to 30 days after the last dose of VAY736, up to approximately 8.8 months
measure: Number of Participants With Dose Reductions and Dose Interruptions of VAY736
timeFrame: Up to 7.8 months
measure: Number of Participants With Dose Reductions and Dose Interruptions of Ibrutinib
timeFrame: Up to 8.5 months
measure: Dose Intensity of VAY736
timeFrame: Up to 7.8 months
measure: Dose Intensity of Ibrutinib
timeFrame: Up to 8.5 months
Secondary outcomes:
measure: CR or CRi Rate at C9 for Expansion Arm A and Arm B by Investigator Per IWCLL
timeFrame: Cycle 9 Day 1 (C9). The duration of each cycle was 28 days.
measure: Posterior Mean of CR or CRi Response Rate at C9 for Expansion Arm A and Arm B (Bayesian Analysis)
timeFrame: Cycle 9 Day 1 (C9). The duration of each cycle was 28 days.
measure: Posterior Probability That the True CR or CRi Response Rate at C9 for Expansion Arm A and Arm B Falls in Pre-defined Activity Intervals (Bayesian Analysis)
timeFrame: Cycle 9 Day 1 (C9). The duration of each cycle was 28 days.
measure: Overall Response Rate (ORR) Assessed by Investigator Per IWCLL in the Dose Escalation Part
timeFrame: Up to approximately 2.5 years
measure: Overall Response Rate (ORR) Assessed by Investigator Per IWCLL in the Dose Expansion Part
timeFrame: Up to approximately 2.7 years
measure: Time to Progression (TTP) in the Dose Escalation Part
timeFrame: Up to approximately 2.5 years
measure: Time to Progression (TTP) in the Dose Expansion Part
timeFrame: Up to approximately 2.7 years
measure: Percentage of Participants With Clearance of Ibrutinib Resistance Mutation During Treatment (up to C9) for Expansion Arm B
timeFrame: Up to Cycle 9 Day 1. The duration of each cycle was 28 days.
measure: Maximum Observed Serum Concentration (Cmax) of VAY736
timeFrame: Pre-infusion and 2, 6, 24, 72, 168 and 336 hours after end of infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of the infusion was approximately 2 hours. 1 cycle=28 days
measure: Time to Reach Maximum Serum Concentration (Tmax) of VAY736
timeFrame: Pre-infusion and 2, 6, 24, 72, 168 and 336 hours after end of infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of the infusion was approximately 2 hours. 1 cycle=28 days
measure: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of VAY736
timeFrame: Pre-infusion and 2, 6, 24, 72, 168 and 336 hours after end of infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of the infusion was approximately 2 hours. 1 cycle=28 days
measure: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
timeFrame: Pre-dose and 0.5, 2, 6 and 24 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 8. 1 cycle=28 days
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Ibrutinib
timeFrame: Pre-dose and 0.5, 2, 6 and 24 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 8. 1 cycle=28 days
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Ibrutinib
timeFrame: Pre-dose and 0.5, 2, 6 and 24 hours post-dose on Cycle 1 Day 1 and Cycle 1 Day 8. 1 cycle=28 days
measure: Number of Participants With Anti-VAY736 Antibodies
timeFrame: Baseline (before first dose) and post-baseline (assessed throughout the VAY736 treatment, up to 7.8 months).
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego - Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Columbus
country: United States
facility: Ohio ST Compr Cancer Ctr James Hosp
state: Ohio
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Salt Lake City
country: United States
facility: Uni of Utah Huntsman Cancer Inst
state: Utah
Study officials:
References:
citation: Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536.