On March 14, three days after a similar announcement from the European Medicines Agency (EMA) the Food and Drug Administration (FDA) issued an alert to healthcare professionals concerning the use of idelalisib (Zydelig) in combination with other cancer treatments. Following reports of increased adverse events including deaths linked to idelalisib during clinical trials, Gilead Sciences, stopped six clinical trials for patients with chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), and indolent non-Hodgkin lymphoma.
Idelalisib is currently approved for use in relapsed CLL, in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities, relapsed follicular B-cell non-Hodgkin lymphoma in patients who have received at least two prior systemic therapies, and relapsed SLL in patients who have received at least two prior systemic therapies. These approvals were based on phase 2 and phase 3 studies that had demonstrated significant evidence of benefit relative to standard therapies. The recent FDA/EMA announcements have not commented on the approved indications for idelalisib.
Doctors at Weill Cornell Medicine take patient safety very seriously. Patients currently taking idelalisib are encouraged to discuss any concerns they may have with their physician.
In this video clip from OncLive, Director of the CLL Research Center, Richard R. Furman, M.D. discusses the new treatments that have changed the care for patients with chronic lymphocytic leukemia (CLL).
ASCO 2015: Safety of Idelalisib in B-cell Malignancies: Integrated Analysis of Eight Clinical TrialsPosted: June 8, 2015
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 DeletionPosted: February 4, 2015
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 email@example.com.
- 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
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 FindingsPosted: December 8, 2014
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.
Earlier today the prestigious journal Cancer Discovery published the results of our program’s latest work in mantle cell lymphoma. Although previous clinical trials have demonstrated the effectiveness of ibrutinib in treating patients with mantle cell lymphoma, researchers also noted that some patient’s lymphoma developed ibrutinib resistance during treatment. Our findings revealed some insight into why this resistance occurs and offers several potential treatment strategies for patients who develop ibrutinib resistance. Based on their findings,
“…the researchers devised two treatment strategies that they tested in lymphoma cell lines. Both involve serial use of two anti-cancer drugs — the first to weaken or “prime” the cancer cells, and the second to deliver an added impact. Both use the experimental agent palbociclib (which selectively inhibits two cell-cycle promoting proteins, CDK4 and CDK6) to slow down the cancer’s growth and sensitize cells to the killing power of a second drug.”
As the study’s lead researcher, Dr. Selina Chen-Kiang commented,
“While for many patients ibrutinib represents a valuable treatment option, it has limitations, and we have been able to demonstrate how novel therapy combinations that target the cancer’s resistance pathways might possibly work better.”
These results build on years of laboratory and clinical work at WCMC, and they highlight the need for further research such as our ongoing trial with ibrutinib plus palbociclib
If you have any questions please contact us and look to our clinical trials page for our ongoing trials.
For additional information see the press release from the American Association for Cancer Research.