Efficacy Study of Anti-KIR Monoclonal Antibody as Maintenance Treatment in Acute Myeloid Leukemia (EFFIKIR)

Study Overview
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Brief Summary
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Double-Blind Placebo-Controlled Randomized Phase 2 Study evaluating the efficacy of lirilumab (IPH2102/BMS-986015) as Maintenance Treatment administered in elderly patients with Acute Myeloid Leukemia (AML) in first complete remission

Official Title
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Double-Blind Placebo-Controlled Randomized Phase 2 Study of IPH2102 as Maintenance Treatment in Elderly Patients With Acute Myeloid Leukemia (AML) in First Complete Remission

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: IPH2102 at 0.1 mg/kg
* Drug: IPH2102 at 1 mg/kg
* Drug: Placebo (normal saline solution)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary or secondary Acute Myeloid Leukemia (AML, defined according to WHO 2008 criteria), in first CR/CRi (according to the revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia J Clin Oncol. 2003 Dec 15; 21(24):4642-9 see appendix 19.3) following induction chemotherapy and who received 1 or 2 consolidation cycles. Induction chemotherapy should be performed within 6 months before randomization. Consolidation cycle is defined as any chemotherapy administered within 3 months following CR and including aracytine irrespective of the administered dose(s). A minimum of one and maximum of 2 cycles should be administered before enrollment Patients not eligible for an allogeneic hematopoietic cell transplantation Age 60 to 80 ECOG Performance status of 0 or 1 Clinical laboratory values at screening Calculated creatinine clearance (according to MDRD) > 60 ml/min/1.73 m2 Platelet > 75 x 109/l Hemoglobin ≥ 10 g/dl supported or unsupported by transfusions ANC > 1 x 109/l Total Bilirubin levels ≤ 1.5 ULN ALT and AST ≤ 3 ULN Recovery from acute toxicity of previous anti-tumor therapy Male patients who accept and are able to use contraception methods recognized as highly effective. Signed informed consent prior to any protocol specific procedure. Exclusion Criteria: Acute Promyelocytic Leukemia with t (15; 17), or its molecular equivalents (PML-RARA) Favorable risk AML corresponding defined as t(8;21) or inv (16) and t(16;16) and their molecular equivalents (AML-ETO and CBFB-MYH11) Last consolidation completed more than 3 months prior to first dosing Concomitant treatment by chemotherapy, immunotherapy or by systemic corticosteroids Within 28 days prior to first dosing: chemotherapy or systemic corticosteroid treatment History of allogeneic hematopoietic cell transplantation or solid organ transplantation History of high dose chemotherapy with autologous hematopoietic transplantation performed as treatment for AML Use of any investigational agent within 2 months prior to the first dosing Use of growth factors (G- or GM-CSF or EPO) within 28 days prior to first dosing Any irradiation within the last 3 months except for analgesic intent Intermittent or continuous renal replacement therapy Abnormal cardiac status with any of the following Ejection fraction (measured by ultra-sound or radionuclide imaging) <50% Myocardial infarction within the previous 6 months QTc ≥ 480 ms (Bazett's). Current active infectious disease or positive serology for HIV, and/or HCV with detectable viremia and/ or HBV with positive Hbs Antigen and/or negative anti Hbs Antibody Auto-immune disease: Which currently or previously required systemic immunosuppressive or immuno-modulatory therapy (including corticosteroids administered by systemic route) And/or has substantial probability to cause an irreversible injury to any tissue And/or is recent or unstable or has substantial risk to progress and cause severe complications. Serious concurrent uncontrolled medical disorder History of another malignancy (apart from myelodysplastic syndromes, basal cell carcinoma of the skin, or in situ cervix carcinoma) except if free of disease for ≥ 3 years Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPH2102 at 1 mg/kg<br>lirilumab (IPH2102/BMS986015) at 1 mg/kg | Drug: IPH2102 at 1 mg/kg<br>* every 4 weeks<br>* Other names: lirilumab/BMS986015;|
| Experimental: IPH2102 at 0.1 mg/kg<br>lirilumab (IPH2102/BMS986015) at 0.1 mg/kg | Drug: IPH2102 at 0.1 mg/kg<br>* every 3 months<br>* Other names: lirilumab/BMS986015;Drug: Placebo (normal saline solution)<br>* every 4 weeks<br>* Other names: normal saline solution;|
| Placebo Comparator: Placebo (Normal saline solution)<br>Normal saline solution | Drug: Placebo (normal saline solution)<br>* every 4 weeks<br>* Other names: normal saline solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leukemia-Free Survival |  | from date of randomization until the date of first documented relapse, assessed up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Number of Participants with Adverse Events based on full physical examination each treatment visit and collection of AEs | from the time of patient signing the consent form until 28 days after the last administration, or until the patient's last study visit, up to 24 months |