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

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

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

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: IPH2102 at 1 mg/kg; Drug: IPH2102 at 0.1 mg/kg; Drug: Placebo (normal saline solution)

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • CHU d'Amiens
  • Angers, France, 49933
    • CHU Angers
  • Argenteuil, France, 95107
    • Centre Hospitalier Victor Dupouy
  • Bayonne, France, 64100
    • Centre Hospitalier de la Côte Basque
  • Besançon, France, 25030
    • CHU de Besancon
  • Blois, France, 41000
    • CH de Blois
  • Bobigny, France, 93000
    • Hôpital Avicenne
  • Brest, France, 29609
    • Hôpital Morvan CHU Brest
  • Béziers, France, 34500
    • CHG de Béziers
  • Cergy Pontoise, France, 95303
    • CH René Dubos
  • Clamart, France, 92141
    • Hôpital MILITAIRE PERCY
  • Clermont-Ferrand, France, 63003
    • CHU Estaing
  • Corbeil Essonnes, France, 91100
    • Centre Hospitalier Sud Francilien
  • Créteil, France, 94010
    • Hôpital Henri Mondor
  • Grenoble, France, 38043
    • CHU de Grenoble
  • Le Chesnay Cedex, France, 78157
    • Centre Hospitalier de Versailles
  • Lille, France, 59037
    • Hopital Claude Huriez
  • Limoges, France, 87042
    • CHU de Limoges
  • Marseille Cedex 09, France, 13273
    • Institut Paoli - Calmettes
  • Meaux, France, 77104
    • CH de Meaux
  • Montpellier Cedex 5, France, 34295
    • CHU Saint Eloi
  • Mulhouse, France, 68100
    • Centre Hospitalier de Mulhouse
  • Nantes, France, 44000
    • CHU de Nantes
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Nîmes, France, 30029
    • CHU Caremeau
  • Orléans, France, 45067
    • CHR d'Orléans
  • Paris, France, 75012
    • Hopital Saint-Antoine
  • Paris, France, 75010
    • Hôpital Saint-Louis
  • Paris Cedex 15, France, 75743
    • Hopital Necker
  • Perpignan, France, 66000
    • CH Saint-Jean
  • Pessac, France, 33604
    • CHU de Bordeaux - Hopital Haut-Lévêque
  • Pierre Bénite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Poitiers, France, 86021
    • CHU De Poitiers
  • Pringy, France, 74374
    • CHR d'Annecy
  • Reims, France, 51092
    • CHU de Reims
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Saint-Cloud, France, 92210
    • Centre René Huguenin
  • Saint-Quentin, France, 02321
    • CH Saint-Quentin
  • Strasbourg, France, 67098
    • Hôpital Haute Pierre et Hôpital Civil
  • Toulouse, France, 31059
    • CHU Purpan
  • Valenciennes, France, 59322
    • Ch Valenciennes
  • Vandoeuvre Les Nancy, France, 54511
    • CHU de Nancy Hopitaux de Brabois
  • Villejuif, France, 94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Innate Pharma
• Investigators: Principal Investigator: Norbert Vey, MD, Institut Paoli Calmettes Marseille France; Study Chair: Hervé Dombret, MD, ALFA cooperative Group; Study Chair: Norbert Ifrah, MD, GOELAMS Cooperative Group

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): November 17, 2016
• Study Completion (Actual): November 17, 2016

Study Registration Dates

• First Submitted: September 11, 2012
• First Submitted That Met QC Criteria: September 13, 2012
• First Posted (Estimate): September 18, 2012

Study Record Updates

• Last Update Posted (Actual): February 8, 2019
• Last Update Submitted That Met QC Criteria: September 6, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Pharmaceutical Solutions
• Other Study ID Numbers: IPH2102-201