Ibrutinib and Venetoclax in Treating Patients With Chronic Lymphocytic Leukemia After Ibrutinib Resistance

  • STATUS
    Recruiting
  • days left to enroll
    35
  • participants needed
    160
  • sponsor
    Kerry Rogers
Updated on 10 November 2021
cancer
lymphoid leukemia
chronic lymphocytic leukemia
lymphoma
venetoclax
neutrophil count
chemotherapy drugs
beta human chorionic gonadotrophin
ibrutinib

Summary

This phase II trial studies how well the combination of ibrutinib and venetoclax works in treating patients with chronic lymphocytic leukemia whose cancer has stopped responding to ibrutinib alone. Both ibrutinib and venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving ibrutinib and venetoclax together after development of ibrutinib resistance may work better than discontinuing ibrutinib and switching to other chemotherapy drugs.

Description

PRIMARY OBJECTIVES:

I. Overall response rate to combination ibrutinib and venetoclax after 12 cycles (intervention cohort).

II. Rate of mutation negative status after 12 cycles of combination venetoclax and ibrutinib (intervention cohort ).

SECONDARY OBJECTIVES:

I. Incidence of BTK C481S mutations during ibrutinib treatment (observation cohort).

II. Progression-free survival after development of a BTK C481S mutation (observation cohort).

III. Progression-free and overall survival after adding venetoclax to ibrutinib (intervention cohort).

IV. Type and incidence of adverse events during combination ibrutinib and venetoclax treatment in this patient population (intervention cohort).

EXPLORATORY OBJECTIVES:

I. Determine patient and disease characteristics associated with clinical disease progression in a univariable and multivariable analysis (observation cohort).

II. Determine the changes in the allelic frequency of ibrutinib resistance mutations after their development (observation cohort) and after venetoclax is added (intervention cohort).

III. Determine novel resistance mechanisms to ibrutinib and ibrutinib/venetoclax combination therapy by whole exome and ribonucleic acid (RNA) sequencing at baseline and clinical relapse.

IV. Perform BH3 profiling and correlate with response to combination venetoclax and ibrutinib therapy.

OUTLINE: This is a dose-escalation study of venetoclax.

OBSERVATION COHORT: Patients who are taking ibrutinib enter Observation cohort and undergo screening every 3 months for development for genetic mutations. If mutations develop, patients undergo increased screening for development of clinical disease progression. Patients who develop clinical disease progression with or without mutations enter the Intervention cohort.

INTERVENTION COHORT: Patients receive venetoclax orally (PO) daily and ibrutinib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve minimal residual disease (MRD) negative complete remission (CR) after 12 or 24 cycles continue receiving ibrutinib PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months thereafter.

Details
Condition Chronic Lymphocytic Leukemia, Lymphocytic Leukemia, Chronic, Loss of Chromosome 17p, 17p deletion, leukemia chronic lymphocytic, chronic lymphocytic leukemia (cll), small lymphocytic lymphoma
Treatment Ibrutinib, venetoclax
Clinical Study IdentifierNCT03943342
SponsorKerry Rogers
Last Modified on10 November 2021

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