Combination Study of IPH2201 With Ibrutinib in Patients With Relapsed, Refractory or Previously Untreated Chronic Lymphocytic Leukemia

This trial is 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 are planned to be enrolled. During the phase 1b portion of the study, a 3+3
design wil be employed. Four doses are planned to be assessed if the Maximum Tolerated Dose
(MTD) is not previously reached: 1, 2, 4 and 10 mg/kg.

During the phase 2a portion, patients will receive IPH2201 in combination with ibrutinib;
IPH2201 will be given at the dose recommended upon completion of the phase Ib portion.

The primary objective of the phase 1b is to assess the safety of IPH2201 given intravenously
as a single agent and in combination with ibrutinib in patients with relapsed or refractory
Chronic Lymphocytic Leukemia previously treated with at least one line of treatment.

The primary objective of the phase 2a is to evaluate the anti-leukemic activity of the
combination of IPH2201 and ibrutinib in patients with relapsed or refractory Chronic
Lymphocytic Leukemia previously treated with at least one line of treatment.

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