A Safety and Tolerability Extension Trial Assessing Repeated Dosing of Anti-KIR (1-7F9) Human Monoclonal Antibody in Patients With Acute Myeloid Leukaemia

An Open-label, Safety and Tolerability Extension Trial Assessing Repeated Dosing of Anti-KIR (1-7F9) Human Monoclonal Antibody in Patients With Acute Myeloid Leukaemia

The trial is a multi-centre, open-label, safety and tolerability extension trial to the IPH2101-101 (previously NN1975-1733) first human dose trial completed with a larger subject pool at an optimal dose level. The trial is conducted in elderly Acute Myeloid Leukemia (AML) patients over the age of 60 years, in complete remission, and who are not eligible for allogeneic stem-cell transplantation. The dose given to the individual patient will be the same as the patient received in the single dose trial IPH2101-101 and 1 mg/kg or 2 mg/kg for the 12 patients in an additional cohort.

Inclusion Criteria:

1. Informed consent obtained before any trial-related activities (Trial-related activities are any procedure that would not have been performed during normal management of the subject)

2. Acute myeloid leukaemia (AML) according to WHO Criteria

3. Morphological complete remission (CR) defined according to NCI criteria, or CRi with incomplete platelet count recovery only after 1 or 2 cycles of induction chemotherapy, and at least 1, and maximally 6 cycles of consolidation chemotherapy:

   • Absolute neutrophile count > 1x 109/L
   • Platelets > 80x109/L
   • Independency of blood transfusions
   • Less than 5% blasts in bone-marrow
   • No Auer rods
   • No symptoms of disease

4. Life expectancy > 4 months as judged by the Investigator

5. The patient is > or = 60 years of age but < or = 80 years of age

6. The patient has completed participation in the IPH2101-101(previously NN1975-1733)trial with an acceptable safety profile, as judged by the Investigator or is screened for the additional cohort

7. Time since last dose of chemotherapy at least 30 days and no more than 60 days if the patient did not participate in IPH2101-101 trial before

8. Recovery from acute toxicities of all previous anti-leukaemic therapies

9. KIR-expression on patient NK-cells (ability to bind Anti-KIR(1-7F9)) if the patient did not participate in IPH2101-101 trial before

10. ECOG performance status 0, 1 or 2

11. No major organ dysfunction as judged by the Investigator

12. The patients must have the following clinical laboratory values:

    • Serum creatinine < or = 2 md/dL
    • Total bilirubin < or = 1.5 x the upper limit of normal
    • Asparatate aminotransferase (AST) < 3x the upper limit of normal

Exclusion Criteria:

1. Known or suspected allergy to trial product or related products
2. Previous participation in this trial
3. AML classified as FAB M3 (APL, acute promyelocytic leukaemia) or with good prognosis AML i.e. t(8;21)(q22;q22) or inv(16)(p13q22) or t(16;16)(p13;q22) or their molecular equivalents
4. Eligibility for allogeneic haematopoietic transplantation
5. The patient is currently receiving, or has within the last 4 weeks received other investigational anti-leukemic treatment such as cytokine treatment, except Anti-KIR(1-7F9)
6. The patient has received G-CSF treatment within the last 30 days prior to screening
7. Systemic steroid treatment within the last 4 weeks prior to screening
8. Patient has active autoimmune disease
9. Diagnosis of monoclonal gammopathy
10. Patient has active infectious disease
11. Previous leukaemic CNS involvement
12. Cardiac failure (New York Heart Association [NYHA] grade III-IV)
13. Left ventricular ejection fraction (LVEF) less than 45 % of normal evaluated by ultrasound or isotopic evaluation
14. Severe neurological/psychiatric disorder
15. HIV or chronic hepatitis infection
16. Clinical evidence of an active second malignancy
17. Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation
18. Any new medical condition that in the opinion of the Investigator disqualifies the patient for inclusion