Venetoclax With High-dose Ibrutinib for CLL Progressing on Single Agent Ibrutinib

NCT03422393 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 171613
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate whether the combination of venetoclax and ibrutinib (administered up to 840 mg per day) might be useful for the treatment of CLL or SLL that is not responding or no longer responding to treatment with ibrutinib alone. The study will evaluate whether this regimen can reduce the amount of cancerous cells in your body. If you agree, you will receive ibrutinib at a dose of up to 840 mg a day by mouth, as well as venetoclax. Although both of these agents are approved by the FDA for the treatment of CLL or SLL, the combination and the dosing schedule of ibrutinib are considered experimental.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

venetoclax; ibrutinib; high-dose ibrutinib; chronic lymphocytic leukemia; progressive disease; Small Lymphocytic Lymphoma; cancer

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose or biologically active dose.

  Maximum tolerated dose or biologically active dose.

  1 year or more

Secondary Outcomes (4)

• Treatment-emergent adverse events

  2 years or more

• Overall response rate

  2 years or more

• Progression free survival rate at completion of combination therapy

  2 years or more

• Stable disease rate

  2 years or more

Study Arms (1)

venetoclax with high-dose ibrutinib

EXPERIMENTAL

venetoclax with high-dose ibrutinib for the treatment of patients with chronic lymphocytic leukemia with progressive disease on single agent ibrutinib.

Drug: Venetoclax; Drug: Ibrutinib

Interventions

Venetoclax DRUG

On cycle 1, day 1, patients will initiate venetoclax. The dose of venetoclax will ramp-up from 20 mg PO daily to 400 mg PO daily over a 5 week period.

Also known as: Venclexta

venetoclax with high-dose ibrutinib

Ibrutinib DRUG

During the screening period, patients will continue on ibrutinib at their previous tolerated dose, unless required to stop (e.g.: by a preceding clinical trial). On cycle 1, day 1, the dose of ibrutinib will be assigned based on the dose cohort. Patients in cohort 1 will receive ibrutinib 420 mg PO daily. Patients in cohort 2 will receive ibrutinib 560 mg PO daily. Cohort 3 will be 840 mg PO daily.

Also known as: Imbruvica

venetoclax with high-dose ibrutinib

Eligibility Criteria

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

You may qualify if:

• Clinical and phenotypic verification of B cell CLL or SLL and measurable disease.
• Prior therapy: Patients must have been receiving single agent ibrutinib therapy at the time of disease progression. Patient may have received other therapy in combination with ibrutinib earlier in their treatment course.
• Women of childbearing potential (not postmenopausal for at least one year or not surgically incapable of bearing children) must agree not to become pregnant for the duration of the study.
• Adequate hematologic, hepatic and renal function

You may not qualify if:

• Known CNS lymphoma or leukemia
• History of Richter's or prolymphocytic transformation.
• Primary ibrutinib resistance
• Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP)
• History of major surgery within 4 weeks prior to first dose on this study.
• History of prior malignancy, with the exception of adequately treated non-melanoma skin cancer, malignancies treated with curative intent and with no evidence of active disease for more than 3 years, or adequately treated cervical carcinoma in situ without current evidence of disease.
• Active clinically significant cardiovascular disease or history of myocardial infarction within 6 months of first dose.
• Active hepatitis B or C infection.
• Known history of infection with human immunodeficiency virus (HIV).
• Unable to swallow capsules or disease significantly affecting gastrointestinal function.
• History of stroke or intracranial hemorrhage within 6 months of first dose.
• Requires anticoagulation with warfarin or other Vitamin K antagonists.
• Requires treatment with a strong cytochrome P(CYP)450 3A inhibitor.
• Pregnant or breast-feeding women
• Current infection requiring parenteral antibiotics.

Sponsors & Collaborators

• Michael Choi: lead
• Pharmacyclics LLC.: collaborator

Study Sites (1)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Disease Progression; Neoplasms

Interventions

venetoclax; ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; 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

Study Officials

• Michael Choi, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical investigator

Study Record Dates

• First Submitted: January 30, 2018
• First Posted: February 5, 2018
• Study Start: May 1, 2018
• Primary Completion: August 1, 2024
• Study Completion (Estimated): August 1, 2028
• Last Updated: July 5, 2024

Record last verified: 2024-07

Locations

US (1)