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.
Condition or disease | Intervention/treatment | Phase |
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Chronic Lymphocytic Leukemia | Drug: During Venetoclax | Phase 2 |
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:
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:
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 50 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Basic Science |
Official Title: | Early Clonal Dynamics During Venetoclax Treatment for Chronic Lymphocytic Leukemia (CLL) |
Actual Study Start Date : | June 26, 2019 |
Estimated Primary Completion Date : | June 30, 2022 |
Estimated Study Completion Date : | June 30, 2022 |
Arm | Intervention/treatment |
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Experimental: Relapsed/Refractory CLL pts
Ages 18 and older
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Drug: During Venetoclax
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.
|
Ages Eligible for Study: | 18 Years to 90 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
-INCLUSION CRITERIA:
Active disease as defined by at least one of the following (iwCLL consensus criteria):
Evidence of progressive marrow failure as manifested by the development of, or worsening of
EXCLUSION CRITERIA:
Known additional malignancy that is progressing or requires active treatment.
--Note: Exceptions include basal cell carcinoma of skin, squamous cell carcinoma of skin, and in situ cervical cancer that has undergone potentially curative therapy. Further exceptions include other cancers from which the subject has been diseasefree for > 2 years, cancers which will not limit survival to < 2 years or cancers in remission receiving endocrine therapy.
Severe psychiatric illness/social situations or cognitive impairment that would limit the patient s ability to tolerate and/or comply with study requirements
Contact: Emeline M Maddux | (301) 451-7094 | emeline.maddux@nih.gov |
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 prpl@cc.nih.gov |
Principal Investigator: | Christopher MT Pleyer, M.D. | National Heart, Lung, and Blood Institute (NHLBI) |
Tracking Information | |||||
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First Submitted Date ICMJE | June 13, 2019 | ||||
First Posted Date ICMJE | June 14, 2019 | ||||
Last Update Posted Date | May 4, 2021 | ||||
Actual Study Start Date ICMJE | June 26, 2019 | ||||
Estimated Primary Completion Date | June 30, 2022 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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. ] | ||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Early Clonal Dynamics During Venetoclax Treatment for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) | ||||
Official Title ICMJE | Early Clonal Dynamics During Venetoclax Treatment for Chronic Lymphocytic Leukemia (CLL) | ||||
Brief 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. |
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Detailed 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:
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:
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Basic Science |
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Condition ICMJE | Chronic Lymphocytic Leukemia | ||||
Intervention ICMJE | Drug: During Venetoclax
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.
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Study Arms ICMJE | Experimental: Relapsed/Refractory CLL pts
Ages 18 and older
Intervention: Drug: During Venetoclax
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
50 | ||||
Original Estimated Enrollment ICMJE |
55 | ||||
Estimated Study Completion Date ICMJE | June 30, 2022 | ||||
Estimated Primary Completion Date | June 30, 2022 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
-INCLUSION CRITERIA:
EXCLUSION CRITERIA:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 90 Years (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03986034 | ||||
Other Study ID Numbers ICMJE | 190111 19-H-0111 |
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Has Data Monitoring Committee | Not Provided | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Responsible Party | National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ) | ||||
Study Sponsor ICMJE | National Heart, Lung, and Blood Institute (NHLBI) | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | National Institutes of Health Clinical Center (CC) | ||||
Verification Date | April 30, 2021 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |