Ibrutinib is a Highly Effective Therapy for Patients with Relapsed or Refractory CLL or SLL with 17p deletion: Results from the Phase II RESONATE -17 Trial

Picture3By Dr. Richard Furman, MD

Patients with chronic lymphocytic leukemia (CLL) with deletion of the short arm of chromosome 17 (del 17p) follow an aggressive clinical course and demonstrate a median survival of less than 2 years. Ibrutinib is a first-in-class inhibitor of Bruton’s tyrosine kinase (BTK), currently approved as treatment for CLL patients relapsed after one prior therapy or patients with del 17p at any line of therapy. Ibrutinib’s initial approval was based upon phase II data published in June 2013. The expanded approval is based upon results from the RESONATE trial comparing ibrutinib to ofatumumab.

At the 56th annual meeting of the American Society of Hematology (ASH), investigators presented the results of the phase II RESONATE -17 (PCYC-1117-CA) study investigating ibrutinib in relapsed CLL patients with deletion of 17p.

The study was designed to evaluate the efficacy and safety of single-agent ibrutinib as treatment of patients with relapsed or refractory CLL with del 17p or small lymphocytic leukemia (SLL). 144 patients (137 CLL patients, 7 SLL patients)  were enrolled and received ibrutinib 420 mg once daily until progression. The primary endpoint was overall response rate (ORR), with secondary endpoints including duration of response (DOR), progression-free survival (PFS), and safety of ibrutinib.

At a median follow up of 13 months, the median PFS and DOR had not been reached. At 12 months, 79.3% of patients were alive and progression-free, and 88.3% of responders were progression-free, with only 20 patients (13.9%) reporting progressive disease. At the time of data cut, the median treatment duration was 11.1 months, and 101 of 144 patients (70%) continued treatment with ibrutinib.

Efficacy results were consistent with earlier results, and the PFS compares favorably to that of treatment-naïve del 17p CLL patients receiving FCR or alemtuzumab. These results support ibrutinib as an effective therapy for patients with del 17p CLL/SLL.

Updated Efficacy Results of Ibrutinib Compared with Ofatumumab in Relapsed CLL (RESONATE Trial), with Analysis of Genetic and Prognostic Subgroups

Picture3By Dr. Richard Furman, MD

The role of various prognostic factors in CLL/SLL is not yet fully understood, including the implications of new genetic markers associated with high risk. Ibrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor that is approved for the treatment of CLL patients who have received at least 1 prior therapy, and for patients with 17p deletion CLL. In results presented before the 56th annual meeting of the American Society of Hematology, updated efficacy results from the phase 3 RESONATE (PCYC-1112) study comparing ibrutinib to ofatumumab were reported.

In the phase III study 391 randomized patients received 420 mg daily of ibrutinib or ofatumumab daily, until disease progression or unacceptable toxicity for up to 24 weeks. During an interim analysis at the median follow up of 9.4 months, patients in the ofatumumab arm were provided access to the ibrutinib arm.

Comparatively, progression free survival (PFS) was significantly longer for ibrutinib compared to ofatumumab. Overall survival (OS) was significantly better for ibrutinib compared to ofatumumab, with 18-month OS rates of 85% and 78% respectively. Higher number of prior therapies (≥3) and 11q deletion were associated with significantly lower 12-month PFS rate for ofatumumab, but not for ibrutinib. The overall response rate (ORR) for ibrutinib versus ofatumumab was 90% to 25%. Compared to ofatumumab, ibrutinib improved 12-month PFS and ORR regardless of baseline genetics, complex cytogenetics, or number of prior therapies. No significant difference in 12-month PFS was observed in ibrutinib treated patients with or without del(17p) or for those who developed lymphocytosis compared to those without lymphocytosis. Median treatment duration was longer for ibrutinib versus ofatumumab and was 16 to 5 months respectively.

In this one on one comparison ibrutinib significantly outperformed ofatumumab in PFS, OS, and ORR in patients with CLL/SLL with at least one prior therapy. These results are consistent with previously published findings, and provide further evidence for the clinical utility  of ibrutinib in patients with CLL.

New Clinical Trial: Ibrutinib in Relapsed/Refractory CLL/SLL with 17p Deletion

Update: this study is closed to enrollment. 

The Weill Cornell Lymphoma Program is now recruiting men and women with relapsed or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) with 17p deletion for a new clinical trial evaluating the experimental drug ibrutinib. The study sponsor is Pharmacyclics, and the principal investigator at Weill Cornell is Dr. Richard Furman. 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
  • Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) with 17p deletion
  • Relapsed or refractory disease after receiving at least one prior line line of systemic therapy which included at least two cycles of chemotherapy or immunotherapy for CLL/SLL
  • Detailed eligibility reviewed when you contact the study team
Study Details

Ibrutinib (also known as PCI-32765) is a type of drug called a kinase inhibitor; the drug blocks an enzyme that helps cancer cells live and grow. By blocking the enzyme, it is possible that ibrutinib will kill cancer cells or stop them from growing.

The purpose of the study is to determine whether ibrutinib is safe and effective in treating CLL/SLL with 17p deletion.

Treatment Plan

All study participants will receive ibrutinib; there is no placebo in this study. Participants will take 3 capsules by mouth once a day and continue on treatment as long as they are responding to therapy and not experiencing unacceptable side effects.