VAY736 in Combination With Ibrutinib in Patients With CLL on Ibrutinib

NCT03400176 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: CVAY736Y21025R01CA177292-09
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 5

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.

Conditions

Chronic Lymphocytic Leukemia (CLL)

Keywords

Ibrutinib; VAY736; Chronic lymphocytic leukemia; CLL; Bruton's Tyrosine Kinase; BTK mutation

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Dose-Limiting Toxicities (DLTs) in Cycle 1 (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 28 days of treatment with the combination of VAY736 and ibrutinib and meets the criteria defined in the study protocol. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.

  28 days

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. For CTCAE v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE. All patients were followed for a 30-day safety follow-up period subsequent to completion of VAY736 therapy. No new AEs or SAEs were collected beyond the 30-day safety follow-up or during the efficacy follow up period.

  From first dose of study treatment up to 30 days after the last dose of VAY736, up to approximately 8.8 months

• Number of Participants With Dose Reductions and Dose Interruptions of VAY736

  For patients who did not tolerate the protocol-specified dosing schedule of the study drugs, dose adjustments could be permitted in order to allow the patient to continue study treatment.

  Up to 7.8 months

• Number of Participants With Dose Reductions and Dose Interruptions of Ibrutinib

  For patients who did not tolerate the protocol-specified dosing schedule of the study drugs, dose adjustments could be permitted in order to allow the patient to continue study treatment.

  Up to 8.5 months

• Dose Intensity of VAY736

  Dose intensity of VAY736 was calculated as: Actual Cumulative dose (mg/kg) / (Duration of exposure in weeks/2)

  Up to 7.8 months

• Dose Intensity of Ibrutinib

  Dose intensity of ibrutinib was calculated as: Actual Cumulative dose (mg) / (Duration of exposure in days)

  Up to 8.5 months

Secondary Outcomes (15)

• CR or CRi Rate at C9 for Expansion Arm A and Arm B by Investigator Per IWCLL

  Cycle 9 Day 1 (C9). The duration of each cycle was 28 days.

• Posterior Mean of CR or CRi Response Rate at C9 for Expansion Arm A and Arm B (Bayesian Analysis)

  Cycle 9 Day 1 (C9). The duration of each cycle was 28 days.

• 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)

  Cycle 9 Day 1 (C9). The duration of each cycle was 28 days.

• Overall Response Rate (ORR) Assessed by Investigator Per IWCLL in the Dose Escalation Part

  Up to approximately 2.5 years

• Overall Response Rate (ORR) Assessed by Investigator Per IWCLL in the Dose Expansion Part

  Up to approximately 2.7 years

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Increasing doses of VAY736 in combination with a fixed dose of ibrutinib.

Drug: VAY736; Drug: ibrutinib

Dose expansion

EXPERIMENTAL

Evaluation of the MTD/RD of the combination of VAY736 and ibrutinib that was identified in dose escalation.

Drug: VAY736; Drug: ibrutinib

Interventions

VAY736 DRUG

Experimental

Dose Escalation; Dose expansion

ibrutinib DRUG

Approved medication

Also known as: Imbruvica

Dose Escalation; Dose expansion

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• Known history of HIV
• Active hepatitis B or C infection
• Receipt of attenuated vaccine within 2 weeks prior to starting study treatment.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

University of California San Diego - Moores Cancer Center

La Jolla, California, 92093-0658, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

Ohio ST Compr Cancer Ctr James Hosp

Columbus, Ohio, 43210, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Uni of Utah Huntsman Cancer Inst

Salt Lake City, Utah, 84103, United States

Location

Related Publications (1)

• 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.

  PMID: 34398557 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ianalumab; ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: January 17, 2018
• Study Start: April 9, 2018
• Primary Completion: September 29, 2023
• Study Completion: September 29, 2023
• Last Updated: May 16, 2025
• Results First Posted: May 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)