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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02557516
Recruitment Status : Terminated (Sponsor decision)
First Posted : September 23, 2015
Results First Posted : December 17, 2019
Last Update Posted : December 17, 2019
Sponsor:
Information provided by (Responsible Party):
Innate Pharma

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

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: monalizumab Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 9, 2015
Actual Primary Completion Date : October 29, 2018
Actual Study Completion Date : September 25, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Ibrutinib

Arm Intervention/treatment
Experimental: Phase 1 Level 1 - 1 mg/kg
In phase 1, Monalizumab given at the first dose level of 1 mg/kg.
Drug: monalizumab

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.

Other Names:
  • Anti-NKG2A
  • IPH2201

Experimental: Phase 1 Level 2 - 2 mg/kg
In phase 1, Monalizumab given at the second dose level of 2 mg/kg.
Drug: monalizumab

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.

Other Names:
  • Anti-NKG2A
  • IPH2201

Experimental: Phase 1 Level 3 - 4 mg/kg
In phase 1, Monalizumab given at the third dose level of 4 mg/kg.
Drug: monalizumab

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.

Other Names:
  • Anti-NKG2A
  • IPH2201

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

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.

Other Names:
  • Anti-NKG2A
  • IPH2201




Primary Outcome Measures :
  1. Number of Dose Limiting Toxicities [ Time Frame: 8 weeks ]
    Number of dose-limiting toxicities, measured during the phase 1, dose escalation, part of the study.

  2. Rate of Complete Response (CR) [ Time Frame: CR assessed 52 weeks after the beginning of combination treatment ]
    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.


Secondary Outcome Measures :
  1. Best Overall Response / Remission Rates [ Time Frame: From beginning of study drug treatment to the end of study (up to 24 months) ]

    Measure of best overall response at any time during the study. cCR: confirmed complete response/remission; uCR: unconfirmed complete response / remission; PR: partial response/remission; SD: stable disease; PD: progressive disease.

    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.

    In order to have a confirmed CR (cCR), the CR must be confirmed by a scan and a bone marrow assessment assessed at least 2 months after the first occurrence of CR. Otherwise it would be an unconfirmed CR (uCR).


  2. Duration of Remission [ Time Frame: Up to 24 months ]
    The duration of remission (DOR) is defined as the time from the date of first evaluation of the remission (cCR, uCR or PR) to the first documentation of progressive disease, relapsed disease or death. In case an assessment of progressive / relapsed disease or death does not exist, the DOR was censored at the time of the last disease assessment date. The DOR was calculated only for the patients with a remission that was assessed at 52 weeks.

  3. Progression Free Survival [ Time Frame: Up to 24 months ]
    The Progression Free Survival (PFS) is defined as the time from first dose administration until the occurrence of progressive disease, relapsed disease or death from any cause. Patients without an event at the time of the analyse were censored at his or her last disease assessment date. Patients with no post-Baseline assessment were censored at the day of the first dose administration.

  4. Overall Survival [ Time Frame: Up to 24 months. ]
    The overall survival (OS) is defined as the time from first dose administration until death from any cause. Alive patients were censored at the most recent date they were known to be alive. Subjects with no assessment post-Baseline were censored at the day of the first dose administration.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02557516


Locations
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United States, Ohio
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Innate Pharma
Investigators
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Principal Investigator: Kerry A Rogers, MD Ohio State University
  Study Documents (Full-Text)

Documents provided by Innate Pharma:
Statistical Analysis Plan  [PDF] March 8, 2019
Study Protocol  [PDF] August 12, 2016

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Responsible Party: Innate Pharma
ClinicalTrials.gov Identifier: NCT02557516    
Other Study ID Numbers: IPH2201-202
First Posted: September 23, 2015    Key Record Dates
Results First Posted: December 17, 2019
Last Update Posted: December 17, 2019
Last Verified: December 2019
Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell