Tag: leukemia cancer

FDA Alert on Idelalisib in Combination with other Cancer Treatments

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.

New Clinical Trial: A Phase 2 Study of the Efficacy & Safety of ACP-196 in Patients with Relapsed/Refractory CLL who are Intolerant to Ibrutinib Therapy

The Weill Cornell Lymphoma Program has recently opened a new research study for men and women with previously-treated chronic lymphocytic leukemia (CLL) who are intolerant to ibrutinib. The study is sponsored by the Acerta Pharma BV and the principal investigator is John Allan, MD. For more information about the study, please call Amelyn Rodriguez at 212-746-1362 or email her at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women age 18 and older.
  • Diagnosis of CLL.
  • At least one prior therapy for CLL.
  • Intolerant to ibrutinib.
  • Detailed eligibility reviewed when you contact the study team.

Study Summary

Btk inhibition is an established therapeutic intervention for the treatment of CLL. In February 2014, ibrutinib (IMBRUVICA®) monotherapy, the first Btk inhibitor developed for clinical use, was approved in the United States for the treatment of patients with CLL who have had ≥ 1 prior therapy or 17p deletion based on high response rates with few drug-related toxicities. However, ibrutinib is not without its adverse reactions. This study will evaluate the safety and efficacy of the second-generation Btk inhibitor, ACP-196, in subjects who have previously discontinued ibrutinib therapy due to adverse reactions. Preliminary data to date suggests that ACP-196 is very well tolerated and has robust activity as a single agent in the treatment of subjects with relapsed/refractory CLL. Additionally, PK/PD results show the 100-mg BID regimen produces optimal target coverage over 24 hours, which may provide greater clinical benefit than the QD regimen of ibrutinib. This study will explore whether ACP-196, as an alternative Btk inhibitor, with a potentially distinct safety profile, may fill an unmet need in therapeutic options for patients who are intolerant to ibrutinib.

Subjects will receive ACP-196 orally twice daily continuously throughout the study as long as they are responding to therapy and not experiencing unacceptable side effects. Subjects who are continuing to tolerate and derive clinical benefit from treatment at the end of the trial may continue to receive their study treatment after discussion with the medical monitor. After discontinuing treatment, subjects will remain in long-term follow-up until loss to follow-up, consent withdrawal, or study closure.

FDA Expedites Review of New CLL Treatment

The Backstory

DRFurman_5284In May 2015, the Federal Drug Administration (FDA) granted venetoclax a breakthrough therapy designation for treating patients with relapsed or refractory chronic lymphocytic leukemia (CLL) with a specific genetic alteration – the 17p deletion. A second FDA breakthrough therapy designation was granted to venetoclax earlier this month for use in combination with rituximab (Rituxan) to treat patients with relapsed/refractory CLL. Last week, the FDA announced that they are granting “Priority Review” to venetoclax. This means that the treatment has been shown to be so effective compared to standard treatment options that the FDA is committed to allocating significant resources to further evaluate it. The label of Priority Review can be of great help in getting new, promising treatment options to more people as quickly as possible.

What is venetoclax?

Venetoclax (also known as ABT-199) is an oral inhibitor of the bcl-2 (B-cell lymphoma 2) protein. BCL-2 protein plays a critical role in preventing cells from undergoing apoptosis (cell death), including CLL cells.

Why did the FDA decide to grant Priority Review to venetoclax?

This Priority Review status is based upon results presented by investigators at the 2015 annual meeting of the American Society of Hematology (ASH) that took place in early December.

In this study, they found that of the 107 patients treated, 85 patients (79.4%) responded to treatment with venetoclax.

Of these patients who responded, eight patients (7.5%) experienced a complete response, meaning that no detectable levels of cancer remained. Three patients (2.8%) experienced nodular partial response (nPR), while 74 patients (69.2%) experienced partial response. Unlike a complete response a nPR includes some persistent remaining modules of lymphocytes. In the past it was difficult to differentiate these CLL cells from normal cells. However, we now know that patients with nPR do better than patients with partial responses, but not as well as complete responses.

Were there any side effects?

The side effect of primary concern based upon earlier studies was tumor lysis syndrome, which occurs when the CLL cells breakdown too rapidly and release too many of their breakdown products at one time, potentially causing kidney failure and death. Researchers sought to implement strategies to minimize the risk of tumor lysis.  Other side effects were comparable or less prevalent than those experienced by people who received current standard chemotherapy treatment for CLL.

How can you access venetoclax now?

At Weill Cornell Medicine, we have a clinical trial with venetoclax already underway for relapsed/refractory CLL patients who have previously been treated with an inhibitor of the BCR signaling pathway, including idelalisib or ibrutinib. If you are interested in enrolling in or learning more about this clinical trial, please contact Amelyn Rodriguez RN, by email amr2017@med.cornell.edu or phone (212) 746-1362.