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

NCT02557516 | Terminated Phase 1 Results

• 1 other identifier: IPH2201-202
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Dose Limiting Toxicities

  Number of dose-limiting toxicities, measured during the phase 1, dose escalation, part of the study.

  8 weeks

• Rate of Complete Response (CR)

  The rate of complete response (CR) was evaluated using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) grading scale and confirmed by a bone marrow biopsy. Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL), Complete Response (CR) is defined as lymphocytes \<4x109/l, absence of lymphadenopathy, hepatomegaly and splenomegaly at CT scan, no constitutional symptoms, no cytopenia, normocellular bone marrow. Partial Response (PR) is a reduction \> 50% in lymphocytes, lymphadenopathy, spleen or liver, no cytopenia. PD if appearance of any new lesion, or increase in lymphocytes \> 50%, or occurrence of cytopenia attributable to CLL.

  CR assessed 52 weeks after the beginning of combination treatment

Secondary Outcomes (4)

• Best Overall Response / Remission Rates

  From beginning of study drug treatment to the end of study (up to 24 months)

• Duration of Remission

  Up to 24 months

• Progression Free Survival

  Up to 24 months

• Overall Survival

  Up to 24 months.

Study Arms (4)

Phase 1 Level 1 - 1 mg/kg

EXPERIMENTAL

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

Drug: monalizumab

Phase 1 Level 2 - 2 mg/kg

EXPERIMENTAL

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

Drug: monalizumab

Phase 1 Level 3 - 4 mg/kg

EXPERIMENTAL

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

Drug: monalizumab

Phase 2 RP2D - 2 mg/kg

EXPERIMENTAL

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

Drug: monalizumab

Interventions

monalizumab DRUG

During phase 1, patients received monalizumab, IV, at the dose of 1, 2 or 4mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks. During phase 2, patients received monalizumab, IV, at the dose recommended upon completion of phase 1, combined with ibrutinib 420 mg orally, once daily, from the first cycle, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab (from week 0 to week 6) occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.

Also known as: Anti-NKG2A, IPH2201

Phase 1 Level 1 - 1 mg/kg; Phase 1 Level 2 - 2 mg/kg; Phase 1 Level 3 - 4 mg/kg; Phase 2 RP2D - 2 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Innate Pharma: lead

Study Sites (1)

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

monalizumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Due to early termination some of the secondary endpoints could not be evaluated.

Results Point of Contact

• Title: Dr. Agnes BOYER-CHAMMARD, Medical Director
• Organization: Innate Pharma

Agnes.BOYER-CHAMMARD@innate-pharma.fr

+33430303030

Study Officials

• Kerry A Rogers, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2015
• First Posted: September 23, 2015
• Study Start: November 9, 2015
• Primary Completion: October 29, 2018
• Study Completion: September 25, 2019
• Last Updated: December 17, 2019
• Results First Posted: December 17, 2019

Record last verified: 2019-12

Locations

US (1)