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

Innate Pharma

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Chronic Lymphocytic Leukemia

Treatments: Drug: monalizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02557516

IPH2201-202

Details and patient eligibility

About

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

Full 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.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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22 participants in 4 patient groups

Phase 1 Level 1 - 1 mg/kg

Experimental group

Description:

In phase 1, Monalizumab given at the first dose level of 1 mg/kg.

Treatment:

Drug: monalizumab

Phase 1 Level 2 - 2 mg/kg

Experimental group

Description:

In phase 1, Monalizumab given at the second dose level of 2 mg/kg.

Treatment:

Drug: monalizumab

Phase 1 Level 3 - 4 mg/kg

Experimental group

Description:

In phase 1, Monalizumab given at the third dose level of 4 mg/kg.

Treatment:

Drug: monalizumab

Phase 2 RP2D - 2 mg/kg

Experimental group

Description:

In phase 2, Monalizumab given at the Recommended Phase 2 Dose (RP2D) of 2 mg/kg, selected by a safety committee.

Treatment:

Drug: monalizumab