A Study of Idelalisib (GS1101, CAL101) + Ofatumumab in Previously Untreated CLL/SLL

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma Read More

Inclusion Criteria:

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Subjects must have CLL / SLL, as documented by a history at some point of an absolute peripheral blood B cell count > 5000, with a monoclonal B cell population co-expressing CD19, CD5, and CD23, or if CD23 negative, then documentation of the absence of t(11;14) or cyclin D1 overexpression. Alternatively patients with lymphadenopathy in the absence of circulating disease will also be eligible for this study if lymph node biopsy establishes the diagnosis of CLL with the above immunophenotype.
• Participants must have measurable disease (lymphocytosis > 5,000, or palpable or CT measurable lymphadenopathy > 1.5 cm, or bone marrow involvement >30%).
• Subjects must not have received any prior systemic therapy for CLL and currently have an indication for treatment as defined by the IWCLL 2008 Guidelines:
• Massive or progressive splenomegaly; OR
• Massive lymph nodes, nodal clusters, or progressive lymphadenopathy; OR
• Grade 2 or 3 fatigue; OR
• Fever ≥ 100.5°F or night sweats for greater than 2 weeks without documented infection; OR
• Presence of weight loss ≥ 10% over the preceding 6 months; OR
• Progressive lymphocytosis with an increase of ≥ 50% over a 2-month period or an anticipated doubling time of less than 6 months; OR
• Evidence of progressive marrow failure as manifested by the development of or worsening of anemia and or thrombocytopenia.
• ECOG performance status <2 (see Appendix A).
• Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of idelalisib or ofatumumab in participants <18 years of age, children are excluded from this study.
• Participants must have normal organ and marrow function as defined below:
• creatinine <2.0 times upper normal limit, total bilirubin <1.5 times upper normal limit (unless due to disease involvement of liver, hemolysis or a known history of Gilbert's disease)
• ALT <2.5 times upper normal limit (unless due to disease involvement of liver) alkaline phosphatase <2.5 times upper normal limit (unless due to disease involvement of the liver or bone marrow)
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Participants who have had any prior systemic therapy for CLL, or chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) for some other indication prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to ofatumumab or idelalisib.
• Subjects who have current active hepatic or biliary disease (with exception of participants with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study
• Other past or current malignancy that could interfere with the interpretation of outcome. Subjects who have been free of active malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma, or whose malignancy will not interfere with the interpretation of study results, are eligible.
• Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C.
• History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
• Known HIV positive. HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with idelalisib. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.
• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the participant.
• Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
• If HBV DNA is negative, subject may be included but must undergo HBV DNA PCR testing at least every 2 months from the start of treatment until 12 months post treatment. Prophylactic antiviral therapy may be initiated at the discretion of the investigator.
• Positive serology for hepatitis C (HC) defined as a positive test for HepC Ab, in which case reflexively perform an HC RIBA immunoblot assay or hepatitis C viral load to confirm the result. If the confirmatory test is negative the subject will be eligible.
• Pregnant or lactating women.
• Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to 30 days after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.
• Male subjects unable or unwilling to use adequate contraception methods from study start to 30 days after the last dose of protocol therapy.
• Participants using concomitant corticosteroids are allowed as long as the subject is on the equivalent of 20mg/day or less of prednisone and has been on a stable dose for at least two weeks prior to initiating therapy.