combination study of iph2201 (monalizumab) with ibrutinib in relapsed, refractory or previously untreated cll

Conditions: Chronic Lymphocytic Leukemia

Summary: 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.

Eligibility criteria:
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