Early Clonal Dynamics During Venetoclax Treatment for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
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|ClinicalTrials.gov Identifier: NCT03986034|
Recruitment Status : Recruiting
First Posted : June 14, 2019
Last Update Posted : July 10, 2019
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.
To learn about genetic changes that happen during treatment of CLL with venetoclax.
Adults ages 18 and older with relapsed or refractory CLL after at least 1 prior therapy
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:
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.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia||Drug: Venetoclax||Phase 2|
This study aims to study the clonal dynamics and kinetics of response during the ramp-up phase of venetoclax in relapsed or refractory chronic lymphocytic leukemia (CLL).
Key Eligibility Criteria:
- Diagnosis of relapsed or refractory CLL after at least one prior therapy
- Must have designated hematologist/oncologist who has agreed to assume care and continue venetoclax after the ramp-up phase is complete
- Age greater than or equal to 18 years
- ECOG 0-2
Patients with relapsed or refractory CLL 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.
-Determine the proportion of subjects with clonal shift during the ramp-up phase of venetoclax
-Determine response kinetics of venetoclax therapy in the peripheral blood, lymph nodes and bone marrow
- 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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||55 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Early Clonal Dynamics During Venetoclax Treatment for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)|
|Actual Study Start Date :||June 6, 2019|
|Estimated Primary Completion Date :||January 15, 2020|
|Estimated Study Completion Date :||December 31, 2020|
Experimental: Relapsed/Refractory CLL pts
Ages 18 and older
Patients with relapsed or refractory CLL who have progressed after at least one prior line of treatment will enroll on the study. Subjects will be treated for the duration of the ramp- up phase of venetoclax at the NIH Clinical Center and receive primary response assessment after reaching the maximum dose of venetoclax. After the ramp-up phase is complete, patients will continue to follow- up at the NIH every 6 months, however subjects' medical care will be transitioned to their local hematologist /oncologist
- Determine the rate of clonal shift during the ramp-up phase of venetoclax [ Time Frame: 5 weeks ]The planned analyses will include descriptive statistics on the proportions of clonal shift probability during the venetoclax ramp-up phase. The clonal shift probabilities will be estimated using the sample proportions and their inferences including confidence intervals and hypotheses testing will be evaluated
- Determine response kinetics of venetoclax therapy in the peripheral blood, lymph nodes and bone marrow [ Time Frame: 5 weeks (Primary Endpoint). F/u every 6 months thereafter until disease progression. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03986034
|Contact: Pia Nierman, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Christopher MT Pleyer, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|