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.


New Options for Treating Patients with Ibrutinib Resistant Mantle Cell Lymphoma

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 resistanceBased 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.


Zydelig Approved by FDA for Patients with CLL, FL, & SLL

Earlier this afternoon the FDA announced the approval of Zydelig (idelalisib) for patients with relapsed chronic lymphocytic leukemia (CLL). Accelerated approval was also granted for the use of  Zydelig in patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL). According to the FDA press release:

“Zydelig’s safety and effectiveness to treat relapsed CLL were established in a clinical trial of 220 participants who were randomly assigned to receive Zydelig and Rituxan or placebo and Rituxan. The trial was stopped for efficacy following the first pre-specified interim analysis point, which showed participants treated with Zydelig and Rituxan lived 10.7 months without their disease progressing (progression-free survival) compared to about 5.5 months for participants treated with placebo and Rituxan. Results from a second interim analysis continued to show a statistically significant improvement for Zydelig and Rituxan over placebo and Rituxan.”

“Zydelig’s safety and effectiveness to treat relapsed FL and relapsed SLL were established in a clinical trial with 123 participants with slow-growing (indolent) non-Hodgkin lymphomas. All participants were treated with Zydelig and were evaluated for complete or partial disappearance of their cancer after treatment (objective response rate, or ORR). Results showed 54 percent of participants with relapsed FL and 58 percent of participants with SLL experienced ORR.”

Commenting on this welcomed development Dr. Richard Furman said, “We are very excited to have idelalisib to add to our armentarium of agents that are now available for use and would like to thank all of the patients and their families who made this possible by participating in the clinical trials.” Look to this blog and our clinical trials page for further developments regarding the use of Zydelig in the treatment of CLL, FL, & SLL patients.


Two Newly Opened Clinical Trials Evaluate Idelalisib in Indolent non-Hodgkin Lymphoma

The Weill Cornell Lymphoma Program has recently opened two clinical trials evaluating the experimental drug idelalisib in previously treated indolent non-Hodgkin lymphomas (iNHL). The sponsor of the trials is Gilead Sciences.  The principal investigator at Weill Cornell is Dr. Peter Martin. For more information about the studies please call Amelyn Rodriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Idelalisib (GS-1101, previously CAL-101) works by blocking some of the cell functions that cause iNHL to grow and survive.

Gilead 0124: Idelalisib in Combination With Rituximab 

This study evaluates the effectiveness of idelalisib combined with rituximab in treating iNHL. Rituximab is FDA-approved for treating iNHL. It is possible that giving rituximab together with idelalisib may have more activity against iNHL than giving rituximab alone.

Key Eligibility

  • Men and women age 18 and older
  • B-cell indolent non-Hodgkin lymphoma (iNHL)
  • Have received prior therapy containing anti-CD20 antibody
  • iNHL is not refractory to rituximab

Click here for a detailed summary of this trial.

Gilead 0125: Idelalisib in Combination With Bendamustine and Rituximab

Update: this study is closed to enrollment. 

This study evaluates the effectiveness of idelalisib combined with bendamustine and rituximab. Rituximab and bendamustine are FDA-approved for treating iNHL. It is possible that giving rituximab and bendamustine together with idelalisib is more effective in treating iNHL than giving rituximab and bendamustine alone.

Key Eligibility

  • Men and women age 18 and older
  • B-cell indolent non-Hodgkin lymphoma
  • Have received prior therapy containing anti-CD20 antibody and chemotherapy
  • iNHL is not refractory to bendamustine

Click here for a detailed summary of this trial.


Idelalisib Study for CLL Patients Ended Early Due to Positive Findings

On October 9, Gilead Sciences Inc., announced an exciting new development for CLL patients. An independent Data Monitoring Committee (DMC) recommended that a Phase 3 study of Idelalisib in previously-treated CLL patients be ended early, due to evidence of efficacy. As Gilead noted,

“This DMC recommendation is based on a predefined interim analysis showing highly statistically significant efficacy for the primary endpoint of progression-free survival in patients receiving idelalisib plus rituximab compared to those receiving rituximab alone. The safety profile of idelalisib was acceptable and consistent with prior experience in combination with rituximab in previously treated CLL. Gilead has informed the U.S. Food and Drug Administration (FDA) of the plan to end the study and will engage in a dialogue with the FDA regarding a regulatory filing in CLL.”

Norbert W. Bischofberger, PhD, Gilead’s Executive Vice President , Research and Development and Chief Scientific Officer explained,

“This is the first Phase 3 study to report positive results for a new class of targeted therapies that inhibit B-cell receptor signaling as a major component of their mechanism of action, an important area of focus in the development of chemotherapy-free regimens in CLL and other B-cell malignancies. We extend thanks to the investigative sites and to the other research collaborators participating in this study, as well as to the patients who volunteered, and we look forward to sharing these data with the hematology community.”

Prominent researchers involved in this study include the Lymphoma Program’s Dr. Richard Furman. Further data from this study will be submitted for upcoming scientific conferences. Please look to this space to follow up with any further announcements regarding this new development.

 Gilead’s full press release can be found here.

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