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

Sponsor
Innate Pharma (Industry)
Overall Status
Completed
CT.gov ID
NCT01256073
Collaborator
(none)
21
Enrollment
6
Locations
1
Arm
79
Duration (Months)
3.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
21 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Study Start Date :
Feb 1, 2007
Actual Primary Completion Date :
Jul 1, 2013
Actual Study Completion Date :
Sep 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: IPH2101

Drug: IPH2101
IPH2101 fully human anti-KIR monoclonal antibody

Outcome Measures

Primary Outcome Measures

  1. To assess safety and tolerability of repeating dosings of Anti-KIR(1-7F9) [every 2 weeks]

    using the US National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE)

Secondary Outcome Measures

  1. To assess the pharmacokinetics upon repeated dosing(s)of Anti-KIR(1-7F9) [every 2 weeks]

  2. To assess the pharmacodynamics upon repeated dosing(s) of Anti-KIR(1-7F9) [every 2 or 4 weeks]

    Degree of KIR-occupancy on patient NK-cells Plasma inflammatory cytokines (IFN-γ, TNF-α, 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

  3. To assess signs of efficacy of repeated dosing(s) with Anti-KIR(1-7F9) [to date of progression diagnosed or until death]

    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

Eligibility Criteria

Criteria

Ages Eligible for Study:
60 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

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

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

  3. 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

  4. 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

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

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

  7. ECOG performance status 0, 1 or 2

  8. No major organ dysfunction as judged by the Investigator

  9. 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Institut Paoli-Calmettes Marseille Marseille Cedex 09 France 13273
2 Hopital Dupuytren LIMOGES Cedex France 87042
3 C.H.R.U. de Nantes - Hotel Dieu NANTES Cedex 1 France 44093
4 Centre Hospitalier Lyon Sud - Hospices Civils de Lyon Pierre-Bénite France 69495
5 Hopital de Purpan Toulouse Cedex 9 France 31059
6 Institut Gustave Roussy Villejuif France 94805

Sponsors and Collaborators

  • Innate Pharma

Investigators

  • Principal Investigator: Norbert Vey, MD, Institut Paoli Calmettes Marseille France

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Innate Pharma
ClinicalTrials.gov Identifier:
NCT01256073
Other Study ID Numbers:
  • IPH 2101-102
First Posted:
Dec 8, 2010
Last Update Posted:
Feb 28, 2014
Last Verified:
Feb 1, 2014
Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute

Study Results

No Results Posted as of Feb 28, 2014