Efficacy Study of Anti-KIR Monoclonal Antibody as Maintenance Treatment in Acute Myeloid Leukemia (EFFIKIR)
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: IPH2102 at 0.1 mg/kg; IPH2102 at 1 mg/kg; Placebo (normal saline solution)
Intervention description: every 3 months; every 4 weeks; every 4 weeks
Intervention MeSH terms: Pharmaceutical Solutions
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 152.0
Sex: All
Minimum age: 60 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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

          2. Patients not eligible for an allogeneic hematopoietic cell transplantation

          3. Age 60 to 80

          4. ECOG Performance status of 0 or 1

          5. 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

          6. Recovery from acute toxicity of previous anti-tumor therapy

          7. Male patients who accept and are able to use contraception methods recognized as
             highly effective.

          8. Signed informed consent prior to any protocol specific procedure.

        Exclusion Criteria:

          1. Acute Promyelocytic Leukemia with t (15; 17), or its molecular equivalents (PML-RARA)

          2. 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)

          3. Last consolidation completed more than 3 months prior to first dosing

          4. Concomitant treatment by chemotherapy, immunotherapy or by systemic corticosteroids

          5. Within 28 days prior to first dosing: chemotherapy or systemic corticosteroid
             treatment

          6. History of allogeneic hematopoietic cell transplantation or solid organ
             transplantation

          7. History of high dose chemotherapy with autologous hematopoietic transplantation
             performed as treatment for AML

          8. Use of any investigational agent within 2 months prior to the first dosing

          9. Use of growth factors (G- or GM-CSF or EPO) within 28 days prior to first dosing

         10. Any irradiation within the last 3 months except for analgesic intent

         11. Intermittent or continuous renal replacement therapy

         12. 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).

         13. 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

         14. 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.

         15. Serious concurrent uncontrolled medical disorder

         16. 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

         17. Any psychological, familial, sociological or geographical condition potentially
             hampering compliance with the study protocol and follow-up schedule.