RECRUITING

Zanubrutinib and Venetoclax as Initial Therapy for Chronic Lymphocytic Leukemia (CLL) With Response-based Obinutuzumab

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

Bruton's tyrosine kinase inhibitors (BTKi), anti-CD20 antibodies, and the B cell lymphoma 2 inhibitor (BCL-2i) venetoclax are drug classes used to treat patients with chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL). Anti-CD20 therapy may not be required for all patients. The investigators hypothesis is that it may be better to give anti-CD20 therapy (obinutuzumab) only to patients that still have detectable cancer in their blood (minimal residual disease \[MRD\]) after being treated with a combination of two oral medications, zanubrutinib (a BTKi ) and venetoclax (a BCL-2i), instead of giving a combination of three drugs to all patients from the start of treatment. This strategy, if effective, will prevent overtreatment with anti-CD20 antibodies; reduce side effects of treatment while potentially increasing MRD negativity rates; and will possibly make the anti-CD20 antibody therapy more effective given the low tumor burden present when utilized. This study will test this hypothesis by treating subjects with 3 cycles of a zanubrutinib monotherapy lead-in, in order to debulk and mitigate tumor lysis risk, followed by 13 cycles of zanubrutinib and venetoclax combination therapy. Subjects who are both peripheral blood and bone marrow MRD negative at the completion of the 13 cycles of combination therapy will stop treatment and enter an observation phase every 3 months. Subjects that are MRD positive will continue combination therapy with zanubrutinib and venetoclax for an additional 6 cycles but also receive 6 cycles of obinutuzumab in order to augment response and increase MRD negative rates for the overall treated cohort.

Official Title

Zanubrutinib and Venetoclax as Initial Therapy for CLL With Obinutuzumab Consolidation in Patients With Minimal Residual Disease Positivity (BruVenG)

Quick Facts

Study Start:2023-05-08
Study Completion:2027-12
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05650723

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 CriteriaExclusion Criteria
  1. * Participant must have confirmed diagnosis of CLL/SLL
  2. * Participant must have indications for treatment
  3. * Participants of childbearing potential must be willing to comply with pregnancy prevention interventions
  1. * Previous exposure to any systemic anti-cancer therapy as a treatment for CLL/SLL, including but not limited to chemotherapy, immunotherapy, radiotherapy, hormone therapy (other than contraceptives, hormone-replacement therapy or megestrol acetate) or investigational therapy.
  2. * History of malignancy except for non-melanoma skin cancers. Participants treated with curative intent via methods of local resection and or locally targeted anticancer treatment and are free of malignancy for at least 5 years from treatment end will be allowed to enroll.
  3. * Requires chronic immunosuppressive therapy for any reason or was treated with immunosuppressive therapy within 6 months of study entry.
  4. * Participants with active autoimmune hemolytic anemia or immune thrombocytopenia purpura.
  5. * Prolymphocytic leukemia or Richter's Transformation.
  6. * Active bleeding, or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease).
  7. * Participant requires warfarin or equivalent vitamin K antagonist.
  8. * Uncontrolled or active significant infection requiring systemic treatment
  9. * History of suspected or confirmed PML
  10. * Myocardial infarction within 6 months before screening.
  11. * Unstable angina within 3 months before screening.
  12. * New York Heart Association class III or IV congestive heart failure
  13. * History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes).
  14. * Patients with stroke or CNS hemorrhage within 6 months.
  15. * Pregnant or breastfeeding.
  16. * Major surgical procedure within 28 days of first dose of study drug.
  17. * Has difficulty with or is unable to swallow oral medication or has significant gastrointestinal disease that would limit absorption of oral medication.
  18. * Participant is positive for human immunodeficiency virus (HIV).
  19. * Known hypersensitivity reactions (e.g., anaphylaxis) to obinutuzumab or any of the excipients, including serum sickness with prior obinutuzumab use.
  20. * Vaccination with live vaccine ≤28 days prior to start of treatment.

Contacts and Locations

Study Contact

Tejasvi Kaur Sahni
CONTACT
646-962-9337
tks4001@med.cornell.edu
Brittany Hobbie
CONTACT
brh4008@med.cornell.edu

Principal Investigator

John Allan, M.D.
PRINCIPAL_INVESTIGATOR
Weill Medical College of Cornell University

Study Locations (Sites)

Weill Cornell Medicine/NewYork-Presberteryian Hospital
New York, New York, 10021
United States

Collaborators and Investigators

Sponsor: Weill Medical College of Cornell University

  • John Allan, M.D., PRINCIPAL_INVESTIGATOR, Weill Medical College of Cornell University

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 Date2023-05-08
Study Completion Date2027-12

Study Record Updates

Study Start Date2023-05-08
Study Completion Date2027-12

Terms related to this study

Keywords Provided by Researchers

  • Chronic Lymphocytic Leukemia
  • CLL
  • Small Lymphocytic Lymphoma
  • SLL

Additional Relevant MeSH Terms

  • Leukemia, Lymphocytic, Chronic, B-Cell