RECRUITING

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

Conditions

Chronic Lymphocytic Leukemia ramp-up Rituximab Tumor Treatment Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

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

Quick Facts

Study Start:2019-06-26

Study Completion:2024-12-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03986034

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	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. 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.

Inclusion Criteria

Exclusion 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

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.
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.

Contacts and Locations

Study Contact

Rachel Adams

CONTACT

(301) 412-3920

rachel.adams@nih.gov

Christopher MT Pleyer, M.D.

CONTACT

(510) 709-6649

christopher.pleyer@nih.gov

Principal Investigator

Christopher MT Pleyer, M.D.

PRINCIPAL_INVESTIGATOR

National Heart, Lung, and Blood Institute (NHLBI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Christopher MT Pleyer, M.D., PRINCIPAL_INVESTIGATOR, National Heart, Lung, and Blood Institute (NHLBI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-06-26

Study Completion Date2024-12-03

Study Record Updates

Study Start Date2019-06-26

Study Completion Date2024-12-03

Terms related to this study

Keywords Provided by Researchers

ramp-up
Rituximab
Tumor
Treatment
Cancer

Additional Relevant MeSH Terms

Chronic Lymphocytic Leukemia