Description:
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.
Title
- Brief Title: Early Clonal Dynamics During Venetoclax Treatment for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
- Official Title: Early Clonal Dynamics During Venetoclax Treatment for Chronic Lymphocytic Leukemia (CLL)
Clinical Trial IDs
- ORG STUDY ID:
190111
- SECONDARY ID:
19-H-0111
- NCT ID:
NCT03986034
Conditions
- Chronic Lymphocytic Leukemia
Interventions
Drug | Synonyms | Arms |
---|
During Venetoclax | | Relapsed/Refractory CLL pts |
Purpose
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.
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:
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
Trial Arms
Name | Type | Description | Interventions |
---|
Relapsed/Refractory CLL pts | Experimental | Ages 18 and older | |
Eligibility Criteria
-INCLUSION CRITERIA:
1. Diagnosis of CLL/SLL which is made according to the updated criteria of the NCI
Working Group16.
2. Active disease as defined by at least one of the following (iwCLL consensus criteria):
- Weight loss greater than or equal to 10% within the previous 6 months
- Extreme fatigue
- Fevers of greater than 100.5 F for greater than or equal to 2 weeks without
evidence of infection
- Night sweats for more than one month without evidence of infection
- Evidence of progressive marrow failure as manifested by the development of, or
worsening of
- Anemia and/or thrombocytopenia
- Massive or progressive splenomegaly
- Massive nodes or clusters or progressive lymphadenopathy
- Progressive lymphocytosis with an increase of >50% over a 2-month period, or
an anticipated doubling time of less than 6 months
3. Must have designated hematologist/oncologist will assume care and provide venetoclax
after the ramp-up phase is complete
4. Must have G6PD testing performed to determine whether rasburicase can be given
5. Must have HLA-testing performed to determine whether allopurinol hypersensitivity
exists
6. Age greater than or equal to 18 years
7. ECOG 0-2
8. Agreement to use acceptable methods of contraception for the duration of venetoclax
treatment if sexually active and able to bear or beget children
9. Willing and able to participate in all required evaluations and procedures in this
study protocol including swallowing capsules without difficulty
10. Able to comprehend the investigational nature of the protocol and provide informed
consent
EXCLUSION CRITERIA:
1. Female patients who are currently pregnant or nursing
2. Any uncontrolled active systemic infection
3. Any life-threatening illness, medical condition, or organ system dysfunction that, in
the investigator s opinion, could compromise the subject s safety or put the study
outcomes at undue risk
4. 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.
5. Richter s Transformation
6. Any prior therapy with BCL-2 inhibitors
7. Concomitant use of strong CYP3A4 inhibitors
8. Disease significantly affecting gastrointestinal function or absorption
9. Uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
10. Concomitant systemic cancer directed therapy (e.g. immunotherapy, chemotherapy,
radiotherapy)
11. Absolute neutrophil count (ANC) <1000/microL, platelets (Plt) <30,000/ microL
12. Serum bilirubin >3 times upper limit of normal (ULN)
13. Severe psychiatric illness/social situations or cognitive impairment that would limit
the patient s ability to tolerate and/or comply with study requirements
- If the PI assesses the decreased ANC and/or Plt to be related to CLL involvement,
patients may still be enrolled in the study, as cytopenias as expected to improve
with treatment of CLL. Patients may receive supportive measures (e.g.
transfusions, IVIG, growth factor support, etc.) to avoid severe cytopenias prior
to and during therapy with venetoclax.
Maximum Eligible Age: | 90 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Determine the rate of clonal shift during the ramp-up phase of venetoclax |
Time Frame: | 5 weeks. |
Safety Issue: | |
Description: | 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 |
Secondary Outcome Measures
Measure: | a. 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. |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | National Heart, Lung, and Blood Institute (NHLBI) |
Trial Keywords
- ramp-up
- Rituximab
- Tumor
- Treatment
- Cancer
Last Updated
August 9, 2021