A Randomized, Phase III Study of Early Intervention with Venetoclax and Obinutuzumab versus Delayed Therapy with Venetoclax and Obinutuzumab in Newly Diagnosed Asymptomatic High-Risk Patients with Chronic Lymphocytic Leukemia (CLL): EVOLVE CLL Study.
Eligibility Criteria Expand/Collapse
Confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) by 2018 International Workshop on CLL, diagnosed within 12 months prior to reg.
CLL-International Prognostic Index (CLL-IPI) Score â‰¥ 4 and/or complex cytogenetics (3+ chromosomal abnormalities).
Cytogenetic and FISH analyses at siteâ€™s CLIA-approved lab within 12 months prior to reg. FISH to detect abnormalities in chromosomes 13q, 12, 11q, and 17p.
TP53 mutation status (if completed) must be obtained within 12 months prior to reg.
IgVH mutational status must be obtained prior to registration (at any time prior to reg).
Serum beta-2 microglobulin level must be obtained within 28 days prior to reg.
Pts must not meet any of the IWCLL specified criteria for active CLL therapy.
Prior/Concurrent Therapy Criteria
High dose corticosteroids and/or IV immunoglobulin for autoimmune complications of CLL must be complete at least 4 weeks prior to reg.
Palliative steroids must be at </= 20 mg/day of prednisone or equivalent corticosteroid at the time of reg.
No prior therapy with anti CD20 monoclonal antibodies.
No current or prior CLL-directed therapy, including non-protocol-related therapy, anti-cancer immunotherapy, experimental therapy, or radiotherapy.
Must not be receiving or planning to receive any other investigational agents before completing protocol therapy.
>/= 18 years of age.
ECOG Performance Status â‰¤ 2.
Adequate marrow function (platelets >/= 100,000/mm3 and ANC >/= 1,000/mm3 within 28 days prior to reg.
Adequate kidney function (creatinine clearance >/= 30mL/min (by Cockroft Gault) within 28 days prior to reg.
Adequate liver function (AST and ALT < 3.0 x ULN and total bilirubin </= 2.0 x ULN (or 5.0 x ULN if history of Gilbertâ€™s disease) within 28 days prior to reg.
Able to take oral medications.
HIV-infected pts must be on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration.
Pts with history of malignancy are allowed providing the cancer has not required active tx within 2 years prior to reg (hormonal therapy is permissible). Exceptions: basal cell, squamous cell skin, or non-melanomatous skin cancer, in situ cervical cancer, superficial bladder cancer not treated with intravesical chemotherapy or BCG within 6 months, localized prostate cancer requiring no more than chronic hormonal therapy, or localized breast cancer requiring no more than chronic hormonal therapy.
No current, clinically significant GI malabsorption.
No uncontrolled active hepatitis B or C. If latent hepatitis B, must agree to take prophylaxis during and for 6 months following active protocol therapy with V-O.
No major surgery within 30 days prior reg or minor surgery within 7 days prior to reg.
No known bleeding disorders.
No history of stroke or intracranial hemorrhage within 6 months prior to reg.
Must not require continued therapy with a strong inhibitor or inducer of CYP3A4/5.
No uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
No currently active, clinically significant cardiovascular disease or Class 3 or 4 congestive heart failure.
No history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to reg.
Must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use an effective contraceptive method.
Specimen Submission Criteria
Must agree to have specimens submitted for translational medicine (MRD) and specimens must be submitted as outlined in Section 15.1.
Must be offered participation in banking for future research. With participantâ€™s consent, specimens must be submitted as outlined in Section 15.3.
Quality of Life Criteria
Pts who are able to complete patient reported outcome (PRO) forms in English, Spanish, French, German, Russian or Mandarin must agree to participate in QOL. (Those pts who are unable to read and write in those languages may be registered to S1925 without QOL.)
Publication Information Expand/Collapse
Randomized, Phase III Study of Early Intervention with Venetoclax and Obinutuzumab versus Delayed Therapy with Venetoclax and Obinutuzumab in Newly Diagnosed Asymptomatic High-Risk Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Cll/Sll): Evolve Cll/Sll Study (SWOG S1925; NCT#04269902)