A Phase 3 Extension Study of Duvelisib and Ofatumumab in Participants With CLL/SLL Previously Enrolled in Study IPI-145-07
Condition: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: IPI-145; Ofatumumab
Intervention description: PI3K Inhibitor; Monoclonal antibody
Intervention MeSH terms: Ofatumumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 99.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Phase 3; CLL/SLL; PI3K

Summary:

      A Phase 3 (extension) clinical trial to examine the efficacy of IPI-145 (duvelisib)
      monotherapy or ofatumumab monotherapy in participants with chronic lymphocytic leukemia (CLL)
      or small lymphocytic lymphoma (SLL) who experienced disease progression after treatment with
      IPI-145 or ofatumumab in study IPI-145-07 (NCT02004522).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Received either IPI-145 or ofatumumab while participating in study IPI-145-07 and
             experienced radiologically confirmed disease progression

          -  Diagnosis of active CLL or SLL that met at least one of the IWCLL 2008 criteria for
             requiring treatment

          -  Measurable disease with a lymph node or tumor mass >1.5 centimeters in at least one
             dimension as assessed by computed tomography (CT)

          -  Eastern Cooperative Oncology Group performance status of 0-2

          -  Must have met the following laboratory parameters:

               1. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤3 x
                  upper limit of normal (ULN)

               2. Total bilirubin ≤1.5 x ULN

               3. Serum creatinine ≤2.0 x ULN

               4. Hemoglobin ≥8.0 grams/deciliter (g/dL) with or without transfusion support

               5. Platelet count ≥10,000 microliters (μL) with or without transfusion support

          -  For women of childbearing potential (WCBP): negative serum β-human chorionic
             gonadotropin pregnancy test within one week before first dose (WCBP defined as a
             sexually mature woman who had not undergone surgical sterilization or who had 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 participants who were 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 have used 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/independent ethics committee-approved
             informed consent form before any study-specific screening procedures are performed

        Exclusion Criteria:

          -  Discontinued study participation in Verastem-sponsored IPI-145-07 study

          -  Greater than 3 months from confirmed progressive disease on Study IPI-145-07

          -  History of Richter's transformation or prolymphocytic leukemia

          -  Autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura that was
             uncontrolled or requires >20 mg daily of prednisone (or equivalent) to maintain
             hemoglobin >8.0 g/dL or platelets >10,000 μL without transfusion support

          -  Known central nervous system (CNS) lymphoma or leukemia; participants with symptoms of
             CNS disease must have had a negative CT scan or negative diagnostic lumbar puncture
             prior to first dose

          -  Use of any anticancer medication from documented progressive disease on Study
             IPI-145-07 to enrollment (Note: corticosteroids to manage CLL/SLL-related symptoms
             were allowed)

          -  Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of
             study treatment (defined as requiring IV antimicrobial, antifungal or antiviral
             agents) (Participants on antimicrobial, antifungal or antiviral prophylaxis are not
             specifically excluded if all other inclusion/exclusion criteria are met and there is
             no evidence of active infection at Screening and/or Cycle 1 Day 1 [predose])

          -  Human immunodeficiency virus infection

          -  Prior, current, or chronic hepatitis B or hepatitis C infection

          -  History of alcohol abuse or chronic liver disease (other than metastatic disease to
             the liver)

          -  Unable to receive prophylactic treatment for pneumocystis and herpes simplex virus

          -  Baseline QT interval corrected with Fridericia's method >480 milliseconds Note: this
             criterion did not apply to participants with a right or left bundle branch block

          -  Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ
             of the cervix, bladder, or prostate not requiring treatment. Participants with
             previous malignancies were eligible provided that they had been disease-free for ≥2
             years

          -  History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia
             requiring medication or mechanical control within the last 6 months

          -  Unstable or severe uncontrolled medical condition (for example, unstable cardiac
             function, unstable pulmonary condition), or any important medical illness or abnormal
             laboratory finding that would, in the investigator's judgment, have increased the
             participant's risk while participating in this study

          -  Prior surgery or gastrointestinal dysfunction that may have affected drug absorption
             (for example, gastric bypass surgery, gastrectomy)

          -  Participants to receive duvelisib: Administration of medications or foods that were
             strong inhibitors or inducers of cytochrome P450 3A within 2 weeks of starting
             duvelisib

          -  Major surgery or invasive intervention within 4 weeks prior to first dose

          -  Pregnant or breastfeeding women

          -  Participants to receive ofatumumab: hypersensitivity to ofatumumab or its excipients.