New Clinical Trial for Patients With Relapsed or Refractory CLL

New Clinical Trial for Patients With Relapsed or Refractory CLL

October 15, 2015

A phase I/II trial of IPH2201, an NKG2A checkpoint inhibitor, is being tested with ibrutinib (Imbruvica) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

A phase I/II trial of IPH2201, an NKG2A checkpoint inhibitor, is being tested with ibrutinib (Imbruvica) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

CLL accounts for approximately 25% of all leukemias. Incidence increases with age and the median age of diagnosis is 70 for men, and 74 for women. It is estimated that 15,720 new cases occurred last year in the United States, causing 4,600 deaths.

Professor John Byrd, MD, Director, and Farrukh Awan, MD, Principal Coordinating Investigator, Division of Hematology, Department of Internal Medicine, Ohio State University, said in a press release: “Ibrutinib represents a breakthrough medicine that was approved for the treatment of relapsed and del(17(p13.1) CLL in 2014. However, although ibrutinib induces a high response rate in patients with CLL, responses are rarely complete. Ultimately the disease progresses in a number of patients. Achieving complete responses would be of great interest to potentially prolong remission, and maybe eventually improve survival rate.”1

The trial's primary objective is to evaluate the antileukemic activity of the combination and the primary endpoint for efficacy is complete response rate (CRR), although as stated above, CRR is rare. The secondary objectives are to assess the safety of the combination of IPH2201 and ibrutinib. The trial will take place at the Ohio State University and the plan is to enroll up to 45 patients.

The trial will be conducted in two parts:

  • In the first part of the study, 12 to 24 patients will receive a combination of ibrutinib at the approved dosage and IPH2201; 4 dose levels of IPH2201 up to 10 mg/kg will be explored. Based on previous experience with IPH2201, these dosages are expected to induce saturation of the NKG2A receptor.
  • In the second part of the study, IPH2201 at the dose selected in the dose-escalating part, will be assessed in combination with ibrutinib during 26 cycles.

The hope is that treatment with IPH2201 in combination with ibrutinib will improve the quality of response beyond ibrutinib alone, and achieve complete responses--a higher rate of complete response should lead to improved overall survival.

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