Investigating how venetoclax affects chronic lymphocytic leukemia

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

-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 it's running

• 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

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Low-dose Liposomal Amphotericin B for preventing fungal infections in adults with blood cancers and prolonged neutropenia

  This study tests whether giving a daily 50 mg dose of liposomal amphotericin B can help prevent invasive fungal infections in adults with blood cancers who have prolonged low white blood cell counts.

  Recruiting Haikou Affiliated Hospital of Central South University Xiangya School of Medicine · Hainan, Hainan · NCT07763054

• Venetoclax plus Zanubrutinib for CLL/SLL in frontline or previously treated patients

  This phase II trial tests if venetoclax plus zanubrutinib can safely and effectively treat adults with chronic lymphocytic leukemia or small lymphocytic lymphoma, including those who are newly diagnosed and those who have had prior therapy.

  Recruiting Phase 2 Ohio State University Comprehensive Cancer Center · Columbus, Ohio · NCT07734038

• Tafasitamab plus Acalabrutinib and Venetoclax for newly treated CLL/SLL

  This phase II study tests a combination of tafasitamab, acalabrutinib, and venetoclax in adults who are newly diagnosed with chronic lymphocytic leukemia or small lymphocytic lymphoma to see if it is safe and effective.

  Recruiting at 2 sites Phase 2 City of Hope Medical Center · Duarte, California and 1 other locations · NCT07582159

• Nemtabrutinib and venetoclax in untreated CLL/SLL

  This phase 2 study tests whether combining nemtabrutinib with venetoclax can help people with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.

  Recruiting Phase 2 Ohio State University Comprehensive Cancer Center · Columbus, Ohio · NCT07557056

• NX-5948 plus other medicines for B-cell cancers

  This trial tests NX-5948 in combination with venetoclax, with or without anti-CD20 antibodies, for adults with CLL/SLL or B-cell lymphoma that has returned or worsened or is newly diagnosed but needing treatment.

  Recruiting at 5 sites Phase 1/2 Nurix Therapeutics, Inc. · Aurora, Colorado and 8 other locations · NCT07520006

• NX-5948 vs Pirtobrutinib in R/R CLL/SLL

  This study tests NX-5948 against pirtobrutinib in people with relapsed or refractory CLL/SLL who have previously tried a covalent BTK inhibitor.

  Recruiting at 6 sites Phase 3 Nurix Therapeutics, Inc. · Macon, Georgia and 5 other locations · NCT07516093

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.