Early Clonal Dynamics During Venetoclax Treatment for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Chronic Lymphocytic Leukemia Clinical Trial

Official title: Early Clonal Dynamics During Venetoclax Treatment for Chronic Lymphocytic Leukemia (CLL)

Status Recruiting

Clinical Trial Summary

Background:

The drug venetoclax treats chronic lymphocytic leukemia (CLL). Researchers want to find better treatments for CLL. To do that, they need to learn how the drug affects CLL cancer cells and the immune system.

Objective:

To learn about genetic changes that happen during treatment of CLL with venetoclax.

Eligibility:

Adults ages 18 and older with relapsed or refractory CLL after at least 1 prior therapy

Design:

Participants will be screened under a separate protocol.

In Phase 1, participants will get venetoclax free of charge through the NIH. Venetoclax is started at a low dose. The dose will be increased every week until participants reach their maximum tolerable dose. This usually take about 5 weeks. Participants will visit the NIH at least once per week. Visits will be about 4 hours. They may have to stay in the hospital to be observed.

In Phase 2, participants will continue to get the drug through their local cancer doctor and their health insurance. Patients will also visit the NIH every 6 months, or if their disease progresses.

At the NIH participants will have regular health assessments. These will include physical exams and a review of the medicines they are taking. They will talk about how they are feeling.

The study included the following tests:

Blood draws

CT scans: Participants will lie in a machine that takes pictures of the body (maximum 3 per year)

Bone marrow biopsies: A small amount of marrow will be taken out of the participant s hip bone with a needle.

Optional lymph node biopsies: A small piece of the participant s tissue will be taken out with a needle.

The study will last at least 2 years.

Clinical Trial Description

This study aims to study the clonal dynamics and kinetics of response during the ramp-up phase of venetoclax in chronic lymphocytic leukemia (CLL).

Key Eligibility Criteria:

1. Diagnosis of CLL/SLL (treatment naive or relapsed/refractory)

2. Must have designated hematologist/oncologist who has agreed to assume care and continue venetoclax after the ramp-up phase is complete

3. Age greater than or equal to 18 years

4. ECOG 0-2

Design:

Patients with CLL/SLL will enroll on the study. Subjects will be treated at the NIH Clinical Center for the duration of the ramp-up phase of venetoclax. After the ramp-up phase is complete, subjects will be transitioned to the care of their local hematologist/oncologist and receive venetoclax monotherapy or in combination with other agent(s) at the discretion of the treating oncologist. Subjects will have the option to follow-up at the NIH every 6 months (from initiation of venetoclax) and at (suspected) progression.

Study Objectives:

Primary Objective:

-Determine the proportion of subjects with clonal shift during the ramp-up phase of venetoclax

Secondary Objective:

-Determine response kinetics of venetoclax therapy in the peripheral blood, lymph nodes and bone marrow

Exploratory Objectives:

• Assess relationship between clonal shifts and minimal residual disease (MRD) status, progression free survival (PFS) and overall survival (OS)

• Assess immunologic changes in the peripheral blood and bone marrow during venetoclax treatment

• Assess circulating-tumor DNA in response to treatment during venetoclax treatment ;

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

• NCT number: NCT03986034
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Rachel Adams
• Phone: (301) 412-3920
• Email: rachel.adams@nih.gov
• Status: Recruiting
• Phase: Phase 2
• Start date: June 26, 2019
• Completion date: December 3, 2024