CCTG CLC.3 - EVOLVE CLL/SLL Study

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)

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Population: Hematology - CLL/SLL

Line of therapy: 1L

Intervention: Early vs. Delayed Venetoclax + Obinutuzumab

Key Inclusion Criteria

1. Participants must have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (collectively referred to as CLL throughout) according to the 2018 International Workshop on CLL (see Section 4.0). Participants must have been diagnosed within 12 months prior to registration.

2. Participants must have CLL-International Prognostic Index (CLL-IPI) Score ≥ 4 (See Section 4.3) and/or complex cytogenetics (defined as 3+ chromosomal abnormalities).

3. Cytogenetic AND/OR FISH analyses must be completed at a CLIA-approved laboratory within 12 months prior to registration. FISH panel should use probes to detect for abnormalities in chromosomes 13q, 12, 11q, and 17p.

4. TP53 mutation status (if completed) must be obtained within 12 months prior to registration.

5. IgVH mutational status must be obtained prior to registration (at any time prior to registration).

6. Serum beta-2 microglobulin level must be obtained within 28 days prior to registration.

7. Participants must have ECOG Performance Status ≤ 2.

8. Participants must have adequate marrow function as evidenced by platelet count ≥ 100,000/mm3 and absolute neutrophil count (ANC) ≥ 1,000/mm3 within 28 days prior to registration.

9. Participants must have adequate kidney function as evidenced by creatinine clearance ≥ 30mL/min (by Cockroft Gault) within 28 days prior to registration.

10. Participants must agree to have specimens submitted for translational medicine (MRD) and specimens must be submitted

    
    

Key Exclusion Criteria

1. Treatment with high dose corticosteroids and/or intravenous immunoglobulin for autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment.

2. Steroids used for treatment of conditions other than CLL/SLL must be at a dose of at most 20 mg/day of prednisone or equivalent corticosteroid at the time of registration.

3. Prior therapy with anti CD20 monoclonal antibodies is not allowed.

4. Participants must not have received or be currently receiving any prior CLL-directed therapy, including non-protocol-related therapy, anti-cancer immunotherapy, experimental therapy (with exception of agents approved for emergency access use for the prevention or treatment of COVID-19),or radiotherapy.

5. Participants must not have had major surgery within 30 days prior registration or minor surgery within 7 days prior to registration.

   Participants must not have known bleeding disorders (e.g., von Willebrand’s disease or hemophilia).

6. Participants must not have a history of stroke or intracranial hemorrhage within 6 months prior to enrollment.

7. Participants must not require continued therapy with a strong inhibitor or inducer of CYP3A4/5, as venetoclax is extensively metabolized by CYP3A4/5

8. Participants must not have uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.

9. Participants must not have any currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification

Sponsor: CCTG

CRP Contact:  martha.elbebawy@ladydavis.ca

514-340-8222 ext. 28224

CRP PI: Dr. T. Skamene

Status: Open to accrual