Combination Study of IPH2201 (Monalizumab) With Ibrutinib in Relapsed, Refractory or Previously Untreated CLL

Open Label 1b/2a Trial of a Combination of IPH2201 and Ibrutinib in Patients With Relapsed, Refractory or Previously Untreated Chronic Lymphocytic Leukemia

Combination study of monalizumab (IPH2201) with Ibrutinib in relapsed, refractory or previously untreated Chronic Lymphocytic Leukemia (CLL) patients in 2 parts :

• phase 1 : a 3+3 design to assess the Maximum Tolerated Dose (MTD)
• phase 2: to evaluate the anti-leukemic activity of the combination

This trial was designated to test the hypothesis that the combination of ibrutinib and IPH2201 will result in a substantial complete response (CR) rate, especially CR without minimal residual disease (MRD), as this has been shown to be associated with long-term clinical benefit.

Up to 45 patients were planned to be enrolled. During the phase 1 part a 3+3 dose escalation design was employed. Four doses were planned to be assessed if the Maximum Tolerated Dose (MTD) was not previously reached: 1, 2, 4 and 10 mg/kg.

During phase 2 part, patients received monalizumab in combination with ibrutinib; monalizumab was given at the dose recommended upon completion of the phase I portion.

The primary objective of the phase 1 was to assess the safety of monalizumab given intravenously as a single agent and in combination with ibrutinib in patients with relapsed, refractory or previously untreated Chronic Lymphocytic Leukemia.

The primary objective of the phase 2 was to evaluate the anti-leukemic activity of the combination of monalizumab and ibrutinib in patients with relapsed, refractory or previously untreated Chronic Lymphocytic Leukemia.

Inclusion Criteria:

• Confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL)
• Relapsed, refractory or previously untreated CLL
• CLL requiring treatment; patients must be eligible for ibrutinib therapy
• Age > = 18 years
• Eastern Cooperative Oncology Group performance status of 0-2
• Life expectancy > = 3 months
• Adequate liver and renal function
• Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study participation
• Ability to understand a written informed and consent document
• Signed informed consent prior to any protocol-specific procedures

Exclusion Criteria:

• Patients who have previously received ibrutinib or another inhibitor of Bruton's tyrosine kinase (BTK)
• History of allergic reactions attributed to compounds or similar chemical or biological composition to ibrutinib
• Central nervous system involvement of the CLL
• Abnormal hematological function which is not due to bone marrow failure related to the CLL
• Patients requiring a treatment by oral vitamin K antagonists
• Serious uncontrolled medical disorder
• Medical condition or organ system dysfunction which, in the investigator opinion, could interfere with absorption or metabolism of ibrutinib
• Moderate or severe hepatic impairment
• Active auto-immune disease
• Abnormal cardiac status
• Pregnant women are excluded from study
• Current active infectious disease
• History of another malignancy within 3 years
• History of allogeneic stem cell or solid organ transplantation