Tag: CLL

New First Line Therapy Approved for CLL

The Backstory

Earlier this month, the FDA approved ibrutinib for first-line use in patients with chronic lymphocytic leukemia (CLL). This makes it the first FDA-approved non-chemotherapy option for initial CLL treatment. The approval adds an alternative to current first line standard treatments which include fludarabine, cyclophosphamide, and rituximab as well as chlorambucil and obinutuzumab.

This is the fifth approval granted to ibrutinib by the FDA and third approval related to CLL. The previous FDA-approved indications included previously treated CLL (February 2014) and patients with 17p deletion (July 2014). Other prior approvals included ibrutinib for use as a monotherapy in patients with Waldenstrom’s macroglobulinemia (July 2015) and as a treatment for mantle cell lymphoma patients who received at least one prior therapy (November 2013).

What is ibrutinib?

Ibrutinib is a first-generation oral drug that inhibits Bruton’s tyrosine kinase (BTK), an enzyme that plays a role in the development of B-cells. In CLL, malignant B-cells grow uncontrollably and prevent other blood cells from properly forming. Ibrutinib disrupts the function of BTK, slowing cell growth and promoting cell death in CLL cells.

Why was ibrutinib granted FDA approval?

Ibrutinib was approved based on the results from the RESONATE-2 trial. Ibrutinib was found to have superior results when compared to the standard chemotherapy treatment, chlorambucil, in a large study of older CLL patients who had not previously received any treatment. Overall, there was an 84% decrease in the risk of death when treated with ibrutinib compared to chlorambucil. These results were presented at the latest American Society of Hematology meeting and published in the New England Journal of Medicine. (December 2015)

Were there any side effects?

Side effects related to ibrutinib included diarrhea, fatigue, coughing, and nausea. Few patients required treatment discontinuation or dose reductions due to adverse side effects of the medication.

How can you access ibrutinib? 

Ibrutinib has been approved for use in CLL, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia, and researchers are attempting to optimize its use in those lymphomas while continuing to investigate its use in other forms of lymphoma. To learn more about whether this is the best treatment for you please call us at (646) 962-2064 and make an appointment with one of our physicians. A full list ibrutinib-related trials currently open at Weill Cornell Medicine can be found on our Joint Clinical Trials website, including two trials for patients with CLL.

ACP-196: What You Should Know about this New Agent for B-cell Lymphomas and CLL

What is it?

ACP-196 is a second generation Bruton’s tyrosine kinase (BTK) inhibitor that can be taken orally. It was developed as an alternative to ibrutinib and was designed to be more selective in targeting BTK. Like ibrutinib it inhibits BTK, a protein important in the development, activation, proliferation, and survival of B-cells. ACP-196 is currently being investigated as a treatment for various B-cell lymphomas, as well as chronic lymphocytic leukemia (CLL).

How does ACP-196 work?

ACP-196 works by inhibiting the activity of BTK, a protein important in the development of B-cells. By preventing the activation of the B-cell antigen receptor signaling pathway, it slows down the growth of cancerous B-cells caused by the overactive BTK.

Does ACP-196 have any side effects?

The side effects for ACP-196 are acceptable and manageable with very few side effects being considered severe.

What is the difference between ACP-196 and ibrutinib?

ACP-196 and ibrutinib are similar in that they both inhibit BTK using the same binding site. They also are both effective in treating chronic lymphocytic leukemia cells. The difference is that ACP-196 inhibits fewer off target enzymes. By being more specific for BTK, the drug may have fewer side effects than ibrutinib, while maintaining similar anti-cancer activity.

How can I access ACP-196?

There are currently numerous clinical trials opened at Weill Cornell Medicine that use ACP-196 for various indications of CLL and B-cell lymphomas. A full list can be found on our Joint Clinical Trials website.

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.