Tag: Idelalisib

ASCO 2015: Safety of Idelalisib in B-cell Malignancies: Integrated Analysis of Eight Clinical Trials

Picture3By Richard Furman, MD

Idelalisib is a first in class, selective, oral inhibitor of PI3Kδ approved by the FDA for the treatment of chronic lymphocytic leukemia (CLL) in combination with rituximab and as a monotherapy for patients with follicular lymphoma, who have received at least two prior systemic therapies. A recent study sought to analyze the safety profile of idelalisib in 760 subjects with heavily pre-treated and relapsed CLL, non-Hodgkin lymphoma, and other B-cell malignancies, who received idelalisib alone or as part of a combination therapy. Side effects leading to changes in dosing included transaminase elevations (13%), diarrhea/colitis (11%), and rash. Side effects leading to discontinuation of treatment were rare. Patient’s whose dose was interrupted due to adverse events were frequently able to tolerate dosing upon re-challenge. These data demonstrate that idelalisib was well tolerated in patients as a monotherapy or in combination.

New Clinical Trial: Phase 2 Study Evaluating the Efficacy and Safety of Idelalisib in Combination with Rituximab in Patients with Previously Untreated Chronic Lymphocytic Leukemia with 17p Deletion

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with chronic lymphocytic leukemia. The study sponsor is Gilead Sciences, Inc., and the principal investigator at Weill Cornell is Richard Furman, M.D..  For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women age 18 and older
  • Diagnosis of CLL with 17p deletion
  • No prior therapy for CLL other than corticosteroids for disease complications
  • Detailed eligibility reviewed when you contact the study team

Study Details

This clinical trial is for men and women with previously untreated CLL with 17p Deletion.

Patients with 17p deleted CLL have particularly aggressive courses characterized by a lack of response to chemotherapy.  Standard treatment for patients who are previously untreated is chemotherapy that carries significant risks without the likelihood of significant benefit. Idelalisib has demonstrated excellent activity and tolerability in patients with relapsed and refractory 17p deleted CLL. This study will provide more information about whether giving rituximab and idelalisib together can benefit patients with previously untreated CLL who have a 17p deletion.

Subjects will receive rituximab for 8 weeks and Idelalisib continuously throughout the study (up to 10 years) as long as they are responding to therapy and not experiencing unacceptable side effects. Rituximab is administered intravenously once weekly. Idelalisib is administered orally twice daily. After discontinuing treatment, follow-up information will be collected once every year throughout the study (up to 10 years) at clinic visits or through telephone calls.

Subjects will be provided a stipend for each study visit to reimburse the cost of travel and other expenses.

Second Interim Analysis of Idelalisib and Rituximab for Patients with Relapsed CLL Confirms Previous Findings

Picture3By Dr. Richard Furman, MD

There is high unmet need for treatment of unfit patients with relapsed CLL, particularly in those characterized by adverse prognostic factors including del (17p) and/or TP53 mutations. Idelalisib is a first-in-class, targeted, highly selective, oral inhibitor of PI3 Kinase-delta enzyme recently approved for the treatment of relapsed CLL in combination with rituximab. During the 56th annual meeting of the American Society of Hematology (ASH) updated results were presented from a phase III study evaluating idelalisib in combination with rituximab in patients with relapsed CLL.

This study tested the efficacy of idelalisib in combination with rituximab compared to placebo with rituximab in patients with relapsed and refractory CLL who were considered unfit to receive cytotoxic therapy due to comorbidities, poor kidney function, or myelosuppression. 220 randomized patients (110 per group) received idelalisib + rituximab or a placebo + rituximab.  At progression, patients were given the option of enrolling in an extension study where they would receive idelalisib.  The primary endpoint was progression free survival.

At the first interim analysis, the results supported a marked improvement for patients who received idelalisib + rituximab compared with placebo + rituximab, with the median PFS not reached for patients taking idelalisib + rituximab compared with  5.5 months for patients taking the placebo. At 12 months, PFS rates for patients on idelalisib + rituximab was 66% compared to 13% for placebo + rituximab. The benefit favoring idelalisib + rituximab was seen in all risk‑groups. At the time of this analysis, 19 total deaths had occurred on the primary study: 6 on idelalisib + rituximab and 13 on placebo + rituximab.

For patients unfit to receive chemotherapy with relapsed CLL, idelalisib + rituximab demonstrated significant improvement over placebo + rituximab in terms of PFS, ORR, and OS with an acceptable safety profile. These results confirm the 1st interim analysis of the study.