A Safety and Tolerability Extension Trial Assessing Repeated Dosing of Anti-KIR (1-7F9) Human Monoclonal Antibody in Patients With Acute Myeloid Leukaemia

Study Overview
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Brief Summary
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The trial is a multi-centre, open-label, safety and tolerability extension trial to the IPH2101-101 (previously NN1975-1733) first human dose trial completed with a larger subject pool at an optimal dose level. The trial is conducted in elderly Acute Myeloid Leukemia (AML) patients over the age of 60 years, in complete remission, and who are not eligible for allogeneic stem-cell transplantation. The dose given to the individual patient will be the same as the patient received in the single dose trial IPH2101-101 and 1 mg/kg or 2 mg/kg for the 12 patients in an additional cohort.

Official Title
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An Open-label, Safety and Tolerability Extension Trial Assessing Repeated Dosing of Anti-KIR (1-7F9) Human Monoclonal Antibody in Patients With Acute Myeloid Leukaemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: IPH2101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities (Trial-related activities are any procedure that would not have been performed during normal management of the subject) Acute myeloid leukaemia (AML) according to WHO Criteria Morphological complete remission (CR) defined according to NCI criteria, or CRi with incomplete platelet count recovery only after 1 or 2 cycles of induction chemotherapy, and at least 1, and maximally 6 cycles of consolidation chemotherapy: Absolute neutrophile count > 1x 109/L Platelets > 80x109/L Independency of blood transfusions Less than 5% blasts in bone-marrow No Auer rods No symptoms of disease Life expectancy > 4 months as judged by the Investigator The patient is > or = 60 years of age but < or = 80 years of age The patient has completed participation in the IPH2101-101(previously NN1975-1733)trial with an acceptable safety profile, as judged by the Investigator or is screened for the additional cohort Time since last dose of chemotherapy at least 30 days and no more than 60 days if the patient did not participate in IPH2101-101 trial before Recovery from acute toxicities of all previous anti-leukaemic therapies KIR-expression on patient NK-cells (ability to bind Anti-KIR(1-7F9)) if the patient did not participate in IPH2101-101 trial before ECOG performance status 0, 1 or 2 No major organ dysfunction as judged by the Investigator The patients must have the following clinical laboratory values: Serum creatinine < or = 2 md/dL Total bilirubin < or = 1.5 x the upper limit of normal Asparatate aminotransferase (AST) < 3x the upper limit of normal Exclusion Criteria: Known or suspected allergy to trial product or related products Previous participation in this trial AML classified as FAB M3 (APL, acute promyelocytic leukaemia) or with good prognosis AML i.e. t(8;21)(q22;q22) or inv(16)(p13q22) or t(16;16)(p13;q22) or their molecular equivalents Eligibility for allogeneic haematopoietic transplantation The patient is currently receiving, or has within the last 4 weeks received other investigational anti-leukemic treatment such as cytokine treatment, except Anti-KIR(1-7F9) The patient has received G-CSF treatment within the last 30 days prior to screening Systemic steroid treatment within the last 4 weeks prior to screening Patient has active autoimmune disease Diagnosis of monoclonal gammopathy Patient has active infectious disease Previous leukaemic CNS involvement Cardiac failure (New York Heart Association [NYHA] grade III-IV) Left ventricular ejection fraction (LVEF) less than 45 % of normal evaluated by ultrasound or isotopic evaluation Severe neurological/psychiatric disorder HIV or chronic hepatitis infection Clinical evidence of an active second malignancy Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation Any new medical condition that in the opinion of the Investigator disqualifies the patient for inclusion

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPH2101<br> | Drug: IPH2101<br>* IPH2101 fully human anti-KIR monoclonal antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess safety and tolerability of repeating dosings of Anti-KIR(1-7F9) | using the US National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) | every 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the pharmacokinetics upon repeated dosing(s)of Anti-KIR(1-7F9) |  | every 2 weeks | 
| To assess the pharmacodynamics upon repeated dosing(s) of Anti-KIR(1-7F9) | Degree of KIR-occupancy on patient NK-cells Plasma inflammatory cytokines (IFN-γ, TNF-α, IL-1, IL-6) Immunophenotyping (NK-, B- and T-lymphocyte counts and activation status) NK-cell surface markers (activation markers and inhibitory receptors) Functional assay of NK-cell activity only for patient from additional cohort | every 2 or 4 weeks | 
| To assess signs of efficacy of repeated dosing(s) with Anti-KIR(1-7F9) | Reduction in minimal residual disease measured by WT-1 expression in blood and bone marrow Progression-free survival (measured as calendar days from the first dosing of Anti-KIR(1-7F9) (in the IPH2101-101 trial) to date of progression diagnosed or until death by any cause Overall survival measured as calendar days from the first dosing of Anti-KIR (1-7F9) to date of death | to date of progression diagnosed or until death |