A Phase 3 Study of Duvelisib Versus Ofatumumab in Patients With Relapsed or Refractory CLL/SLL (DUO)

Inclusion Criteria

• Diagnosis of active CLL or SLL that meets at least one of the IWCLL 2008 criteria for requiring treatment (Binet Stage ≥ B and/or Rai Stage ≥ I)
• Disease that has progressed during or relapsed after at least one previous CLL/SLL therapy
• Not appropriate for treatment with a purine-based analogue regimen (per National Comprehensive Cancer Network [NCCN] or European Society for Medical Oncology [ESMO] guidelines), including relapse ≤ 36 months from a purine-based chemoimmunotherapy regimen or relapse ≤ 24 months from a purine-based monotherapy regimen
• A cytogenetics or fluorescence in situ hybridization (FISH) analysis of the leukemic cells within 24 months of randomization is required to document the presence or absence of del(17p). Note: if a sample from within 24 months is not available, it should be evaluated as part of the screening laboratory evaluation to inform stratification
• Measurable disease with a lymph node or tumor mass > 1.5 cm in at least one dimension as assessed by computed tomography (CT)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (corresponds to Karnofsky Performance Status [KPS] ≥ 60%)
• Willingness by subject to be randomized to receive either ofatumumab or duvelisib at the dose and schedule defined in the protocol
• Must meet the following laboratory parameters:
• Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤ 3 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN
• Serum creatinine ≤ 2.0 x ULN
• Hemoglobin ≥ 8.0 g/dL with or without transfusion support
• Platelet count ≥ 10, 000 μL with or without transfusion support
• For women of childbearing potential (WCBP): negative serum β-human chorionic gonadotropin (βhCG) pregnancy test within 1 week before randomization (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 24 consecutive months [women ≤ 55 years] or 12 consecutive months [women > 55 years])
• Willingness of male and female subjects who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control from the first dose of study drug to 30 days after the last dose of duvelisib and for 12 months after last dose of ofatumumab. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception
• Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
• Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed

Exclusion Criteria

• History of Richter's transformation or prolymphocytic leukemia
• Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP) that is uncontrolled or requiring > 20 mg once daily (QD) of prednisone (or equivalent) to maintain hemoglobin > 8.0 g/dL or platelets > 10,000 μL without transfusion support
• Refractory to ofatumumab (progression or relapse 6 months prior to study entry is permitted)
• Known central nervous system lymphoma or leukemia; subjects with symptoms of CNS disease must have a negative CT scan or negative diagnostic lumbar puncture prior to randomization
• Use of any of the following medications or procedures within the specified timeframe:
• Use of live or live attenuated vaccines within 30 days prior to randomization
• Chemotherapy, radiation therapy, or ablative therapy within 3 weeks of randomization
• Tyrosine kinase inhibitor within 7 days of randomization
• Other investigational therapy (not included above) within 3 weeks of randomization
• Previous treatment with a PI3K inhibitor or BTK inhibitor
• Ongoing treatment with chronic immunosuppressants (eg, cyclosporine) or systemic steroids > 20 mg prednisone (or equivalent) QD
• History of tuberculosis treatment within the preceding