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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01256073
• Other study ID #: IPH 2101-102
• Status: Completed
• Phase: Phase 1
• First received: December 7, 2010
• Last updated: February 27, 2014
• Start date: February 2007
• Est. completion date: September 2013

Study information

• Verified date: February 2014
• Source: Innate Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: September 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years to 80 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• IPH2101
IPH2101 fully human anti-KIR monoclonal antibody

Locations

Country	Name	City	State
France	Hopital Dupuytren	LIMOGES Cedex
France	Institut Paoli-Calmettes	Marseille	Marseille Cedex 09
France	C.H.R.U. de Nantes - Hotel Dieu	NANTES Cedex 1
France	Centre Hospitalier Lyon Sud - Hospices Civils de Lyon	Pierre-Bénite
France	Hopital de Purpan	Toulouse Cedex 9
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Innate Pharma

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess safety and tolerability of repeating dosings of Anti-KIR(1-7F9)	using the US National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE)	every 2 weeks	Yes
Secondary	To assess the pharmacokinetics upon repeated dosing(s)of Anti-KIR(1-7F9)		every 2 weeks	No
Secondary	To assess the pharmacodynamics upon repeated dosing(s) of Anti-KIR(1-7F9)	Degree of KIR-occupancy on patient NK-cells; Plasma inflammatory cytokines (IFN-?, TNF-a, IL-1, IL-6); Immunophenotyping (NK-, B- and T-lymphocyte counts and activation status); NK-cell surface markers (activation markers and inhibitory receptors); Functional assay of NK-cell activity only for patient from additional cohort	every 2 or 4 weeks	No
Secondary	To assess signs of efficacy of repeated dosing(s) with Anti-KIR(1-7F9)	Reduction in minimal residual disease measured by WT-1 expression in blood and bone marrow; Progression-free survival (measured as calendar days from the first dosing of Anti-KIR(1-7F9) (in the IPH2101-101 trial) to date of progression diagnosed or until death by any cause; Overall survival measured as calendar days from the first dosing of Anti-KIR (1-7F9) to date of death	to date of progression diagnosed or until death	No