Clinical trial NCT01687387: Efficacy Study of Anti-KIR Monoclonal Antibody as Maintenance Treatment in Acute Myeloid Leukemia (EFFIKIR)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Lead sponsor: Innate Pharma
Sponsor class: INDUSTRY
First posted: 2012-09-18
Enrollment: 152
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Leukemia-Free Survival
timeFrame: from date of randomization until the date of first documented relapse, assessed up to 48 months
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 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
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'Amiens
city: Angers
country: France
facility: CHU Angers
city: Argenteuil
country: France
facility: Centre hospitalier Victor Dupouy
city: Bayonne
country: France
facility: Centre hospitalier de la côte Basque
city: Besançon
country: France
facility: CHU de Besançon
city: Blois
country: France
facility: CH de Blois
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Brest
country: France
facility: Hôpital Morvan CHU Brest
city: Béziers
country: France
facility: CHG de Béziers
city: Cergy Pontoise
country: France
facility: CH René Dubos
city: Clamart
country: France
facility: Hôpital Militaire Percy
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Corbeil Essonnes
country: France
facility: Centre hospitalier sud francilien
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Grenoble
country: France
facility: CHU de Grenoble
city: Le Chesnay Cedex
country: France
facility: Centre Hospitalier de Versailles
city: Lille
country: France
facility: Hôpital Claude Huriez
city: Limoges
country: France
facility: CHU de Limoges
city: Marseille Cedex 09
country: France
facility: Institut Paoli - Calmettes
city: Meaux
country: France
facility: CH de Meaux
city: Montpellier Cedex 5
country: France
facility: CHU Saint Eloi
city: Mulhouse
country: France
facility: Centre Hospitalier de Mulhouse
city: Nantes
country: France
facility: CHU de Nantes
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nîmes
country: France
facility: CHU Caremeau
city: Orléans
country: France
facility: CHR d'Orléans
city: Paris Cedex 15
country: France
facility: Hôpital Necker
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Perpignan
country: France
facility: CH Saint-Jean
city: Pessac
country: France
facility: CHU de Bordeaux - Hôpital Haut-Lévêque
city: Pierre Bénite
country: France
facility: Centre hospitalier Lyon Sud
city: Poitiers
country: France
facility: CHU de Poitiers
city: Pringy
country: France
facility: CHR d'Annecy
city: Reims
country: France
facility: CHU de Reims
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Cloud
country: France
facility: Centre René Huguenin
city: Saint-Quentin
country: France
facility: CH Saint-Quentin
city: Strasbourg
country: France
facility: Hôpital Haute Pierre et Hôpital Civil
city: Toulouse
country: France
facility: CHU Purpan
city: Valenciennes
country: France
facility: CH Valenciennes
city: Vandoeuvre Les Nancy
country: France
facility: CHU de Nancy Hôpitaux de Brabois
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Institut Paoli Calmettes Marseille France
name: Norbert Vey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: ALFA cooperative Group
name: Hervé Dombret, MD
role: STUDY_CHAIR
affiliation: GOELAMS Cooperative Group
name: Norbert Ifrah, MD
role: STUDY_CHAIR
References: