Clinical trial NCT02557516: Combination Study of IPH2201 (Monalizumab) With Ibrutinib in Relapsed, Refractory or Previously Untreated CLL
Official title: Open Label 1b/2a Trial of a Combination of IPH2201 and Ibrutinib in Patients With Relapsed, Refractory or Previously Untreated Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Chronic Lymphocytic Leukemia
Lead sponsor: Innate Pharma
Sponsor class: INDUSTRY
First posted: 2015-09-23
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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

Detailed description: 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

Primary outcomes:
measure: Number of Dose Limiting Toxicities
timeFrame: 8 weeks
measure: Rate of Complete Response (CR)
timeFrame: CR assessed 52 weeks after the beginning of combination treatment
Secondary outcomes:
measure: Best Overall Response / Remission Rates
timeFrame: From beginning of study drug treatment to the end of study (up to 24 months)
measure: Duration of Remission
timeFrame: Up to 24 months
measure: Progression Free Survival
timeFrame: Up to 24 months
measure: Overall Survival
timeFrame: Up to 24 months.
Other outcomes:
Locations:
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Kerry A Rogers, MD
role: PRINCIPAL_INVESTIGATOR
References: