Tag: relapsed or refractory CLL/SLL

New Clinical Trial: Study to Determine the Safety, Pharmacokinetics, & Efficacy of Single Agent CC-122 with Rituximab/Ibrutinib in Patients with Relapsed & Refractory CLL/SLL

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with relapsed or refractory CLL/SLL. The study sponsor is the Celegene Corporation, 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 to 79.
  • Diagnosis of CLL/SLL.
  • Must meet the criteria for relapsed and/or refractory disease.
  • Detailed eligibility reviewed when you contact the study team.

Study Summary

This clinical trial is for men and women with relapsed/refractory CLL/SLL.

Subjects on this study will receive the study drug, CC-122, in combination with rituximab or ibrutinib, or as a single agent. CC-122 is an analog of thalidomide and has multiple activities in CLL, including immune modulation (activation of cells in the immune system) and anti-proliferative activity. CC-122 has also been shown to have a tolerable safety profile with some preliminary signs of efficacy with early human experience. Rituximab is a monoclonal antibody directed against a molecule present on the surface of normal B lymphocytes and CLL cells. Ibrutinib is a BTK inhibitor that has received accelerated approval in the United States for patients with CLL who have received at least one prior therapy. This study will provide more information about the efficacy and safety of CC-122 both as a single agent and in combination with rituximab or ibrutinib in subjects with CLL/SLL.

All subjects will receive CC-122 continuously throughout the study as long as they are responding to therapy and not experiencing unacceptable side effects. Some subjects will receive ibrutinib which will be taken continuously throughout the study. Both CC-122 and ibrutinib will be administered orally once daily. Other subjects will receive rituximab which will be administered intravenously on cycle 1 day 1 and 8, and on day 1 of cycle 3, 5, 7, 9, and 11. After discontinuing treatment, subjects will be contacted every 90 days for follow-up information until disease progression, withdrawal of consent, or loss to follow-up.

Subjects may receive up to forty dollars per visit for the reimbursement of travel expenses.

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.

Ibrutinib Promotes a High Frequency of Durable Response in Relapsed/Refractory and Older Treatment Naive CLL Patients

BTK is an essential mediator of B-cell receptor signaling in normal and malignant B-cells.  Ibrutinib (PCI-32765), an oral inhibitor of BTK, promotes apoptosis and inhibits proliferation, migration and adhesion in CLL cells. Chemoimmunotherapy (CIT) treatment approaches such as fludarabine, cyclophosphamide and rituximab have markedly improved outcomes of younger, fit patients as initial or second-line therapy. Unfortunately, fludarabine-based therapy is less well tolerated in the elderly and carries significant risk of cellular immune suppression, myelosupression, and subsequent myeloid neoplasia. Additionally, virtually all patients eventually relapse after fludarabine-based CIT, leading to the need for effective salvage regimens that induce durable remissions.

Recently, at the biennial international workshop on CLL (iwCLL), in Cologne, Germany, Dr. Richard Furman presented final results from a large (n=116 patients) multi-cohort Phase Ib/II trial of ibrutinib in treatment-naive (TN) or relapsed/refractory (RR) CLL/SLL.  Patients demonstrated a high frequency of durable responses extending beyond 24 months in both TN and RR CLL/SLL including those with high-risk genomic features.

Patients who were TN (all age ≥65 years) or RR (≥ 2 prior therapies including a purine analog and with  high-risk (HR) (relapsed within 2 years from combination CIT) were treated with  ibrutinib at fixed doses of 420mg or 840mg daily until disease progression (PD). The study’s primary objective was to determine the safety and response rates of both dosing regimens.  The overall response rates for the TN and RR patients were 84% and 88% respectively.  The progression free survival (PFS) estimated at 26 months for the 85 RR patients is 74% and for the 31 TN patients is 96%. Estimated 26 month overall survival (OS) for 85 RR patients is 78% and for the 31 TN patients is 97%.  Median duration of response, PFS, and OS have not been reached at the time of this analysis.

In conclusion, Ibrutinib monotherapy was found to be highly active, well tolerated, and induced durable responses in CLL patients with high-risk disease, R/R patients, and older TN patients. At present there are ongoing randomized trials comparing the safety profile of ibrutinib with other CLL therapeutic agents. Ongoing CLL trials at Weill Cornell Medical College can be found here.