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

Phase 2

Completed

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

• Registration Number: NCT01687387
• Lead Sponsor: Innate Pharma

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-09-11
• Study First Submitted QC: 2012-09-13
• Study First Posted: 2012-09-18
• Study Start: 2012-10
• Primary Completion: 2016-11-17
• Study Completion: 2016-11-17
• Results First Submitted: 2017-12-15
• Status Verified: 2018-09
• Results First Submitted QC: 2018-09-06
• Last Update Submitted: 2018-09-06
• Results First Posted: 2019-02-08
• Last Update Posted: 2019-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 152

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IPH2102 at 0.1 mg/kg	Placebo (normal saline solution)	lirilumab (IPH2102/BMS986015) at 0.1 mg/kg
IPH2102 at 1 mg/kg	IPH2102 at 1 mg/kg	lirilumab (IPH2102/BMS986015) at 1 mg/kg
IPH2102 at 0.1 mg/kg	IPH2102 at 0.1 mg/kg	lirilumab (IPH2102/BMS986015) at 0.1 mg/kg
Placebo (Normal saline solution)	Placebo (normal saline solution)	Normal saline solution

Primary Outcome Measures

Name	Time	Method
Leukemia-Free Survival	from date of randomization until the date of first documented relapse, assessed up to 48 months

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	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	Number of Participants with Adverse Events based on full physical examination each treatment visit and collection of AEs

Trial Locations

Locations (43)

Hôpital Claude Huriez; 🇫🇷 Lille, France

CHU Angers; 🇫🇷 Angers, France

CHU d'Amiens; 🇫🇷 Amiens, France

Centre hospitalier Victor Dupouy; 🇫🇷 Argenteuil, France

Centre hospitalier de la côte Basque; 🇫🇷 Bayonne, France

CHU de Besançon; 🇫🇷 Besançon, France

Hôpital Avicenne; 🇫🇷 Bobigny, France

CH de Blois; 🇫🇷 Blois, France

Hôpital Morvan CHU Brest; 🇫🇷 Brest, France

CHG de Béziers; 🇫🇷 Béziers, France

CH René Dubos; 🇫🇷 Cergy Pontoise, France

Hôpital Militaire Percy; 🇫🇷 Clamart, France

Centre hospitalier sud francilien; 🇫🇷 Corbeil Essonnes, France

CHU Estaing; 🇫🇷 Clermont-Ferrand, France

Hôpital Henri Mondor; 🇫🇷 Créteil, France

CHU de Grenoble; 🇫🇷 Grenoble, France

Centre Hospitalier de Versailles; 🇫🇷 Le Chesnay Cedex, France

CHU de Limoges; 🇫🇷 Limoges, France

Institut Paoli - Calmettes; 🇫🇷 Marseille Cedex 09, France

CH de Meaux; 🇫🇷 Meaux, France

Centre Hospitalier de Mulhouse; 🇫🇷 Mulhouse, France

CHU Saint Eloi; 🇫🇷 Montpellier Cedex 5, France

CHU de Nantes; 🇫🇷 Nantes, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

CHU Caremeau; 🇫🇷 Nîmes, France

Hôpital Saint-Antoine; 🇫🇷 Paris, France

CHR d'Orléans; 🇫🇷 Orléans, France

Hôpital Necker; 🇫🇷 Paris Cedex 15, France

Hôpital Saint-Louis; 🇫🇷 Paris, France

CH Saint-Jean; 🇫🇷 Perpignan, France

CHU de Bordeaux - Hôpital Haut-Lévêque; 🇫🇷 Pessac, France

CHU de Poitiers; 🇫🇷 Poitiers, France

Centre hospitalier Lyon Sud; 🇫🇷 Pierre Bénite, France

CHR d'Annecy; 🇫🇷 Pringy, France

CHU de Reims; 🇫🇷 Reims, France

Centre Henri Becquerel; 🇫🇷 Rouen, France

Centre René Huguenin; 🇫🇷 Saint-Cloud, France

Hôpital Haute Pierre et Hôpital Civil; 🇫🇷 Strasbourg, France

CH Valenciennes; 🇫🇷 Valenciennes, France

CH Saint-Quentin; 🇫🇷 Saint-Quentin, France

CHU Purpan; 🇫🇷 Toulouse, France

CHU de Nancy Hôpitaux de Brabois; 🇫🇷 Vandoeuvre Les Nancy, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France