Investigating how venetoclax affects chronic lymphocytic leukemia
Early Clonal Dynamics During Venetoclax Treatment for Chronic Lymphocytic Leukemia (CLL)
This study is testing how the medication venetoclax affects people with chronic lymphocytic leukemia during the early stages of treatment to see how it impacts their cancer and overall health.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 75 (estimated) |
| Ages | 18 Years to 85 Years |
| Sex | All |
| Sponsor | National Institutes of Health Clinical Center (CC) NIH |
| Drugs / interventions | chemotherapy, immunotherapy |
| Locations | 1 site (Bethesda, Maryland) |
| Trial ID | NCT03986034 on ClinicalTrials.gov |
What this trial studies
This study aims to explore the genetic changes and clonal dynamics in patients with chronic lymphocytic leukemia (CLL) during the initial ramp-up phase of treatment with venetoclax. Participants will receive venetoclax at a low dose that will be gradually increased over approximately five weeks while being monitored at the NIH Clinical Center. After this phase, patients will transition to their local oncologist for ongoing treatment. The study will assess the relationship between clonal shifts and treatment outcomes, including minimal residual disease status and overall survival.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with relapsed or refractory chronic lymphocytic leukemia after at least one prior therapy.
Not a fit: Patients with treatment-naive CLL or those who do not have a designated oncologist for ongoing care may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could lead to improved treatment strategies for patients with relapsed or refractory CLL.
How similar studies have performed: Other studies have shown promise in understanding clonal dynamics in CLL, but this specific approach with venetoclax is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
-INCLUSION CRITERIA:
1. Diagnosis of CLL/SLL which is made according to the updated criteria of the NCI Working Group.
2. Active disease as defined by at least one of the following (iwCLL consensus criteria):
* Weight loss \>=10% within the previous 6 months
* Extreme fatigue
* Fevers of greater than 100.5 degrees F for \>=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 \>=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.
Where this trial is running
Bethesda, Maryland
- National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: Christine E Gruessner, M.D. — National Heart, Lung, and Blood Institute (NHLBI)
- Study coordinator: Ingrid C Frey
- Email: ingrid.frey@nih.gov
- Phone: (301) 402-0797
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.