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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Innate Pharma
ClinicalTrials.gov Identifier:
NCT01256073
First received: December 7, 2010
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Acute Myeloid Leukemia
Drug: IPH2101
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Innate Pharma:

Primary Outcome Measures:
  • To assess safety and tolerability of repeating dosings of Anti-KIR(1-7F9) [ Time Frame: every 2 weeks ] [ Designated as safety issue: Yes ]
    using the US National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE)


Secondary Outcome Measures:
  • To assess the pharmacokinetics upon repeated dosing(s)of Anti-KIR(1-7F9) [ Time Frame: every 2 weeks ] [ Designated as safety issue: No ]
  • To assess the pharmacodynamics upon repeated dosing(s) of Anti-KIR(1-7F9) [ Time Frame: every 2 or 4 weeks ] [ Designated as safety issue: No ]
    • 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

  • To assess signs of efficacy of repeated dosing(s) with Anti-KIR(1-7F9) [ Time Frame: to date of progression diagnosed or until death ] [ Designated as safety issue: No ]
    • 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


Enrollment: 21
Study Start Date: February 2007
Study Completion Date: September 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IPH2101 Drug: IPH2101
IPH2101 fully human anti-KIR monoclonal antibody

  Eligibility

Ages Eligible for Study:   60 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01256073

Locations
France
Institut Paoli-Calmettes
Marseille, Marseille Cedex 09, France, 13273
Hopital Dupuytren
LIMOGES Cedex, France, 87042
C.H.R.U. de Nantes - Hotel Dieu
NANTES Cedex 1, France, 44093
Centre Hospitalier Lyon Sud - Hospices Civils de Lyon
Pierre-Bénite, France, 69495
Hopital de Purpan
Toulouse Cedex 9, France, 31059
Institut Gustave Roussy
Villejuif, France, 94805
Sponsors and Collaborators
Innate Pharma
Investigators
Principal Investigator: Norbert Vey, MD Institut Paoli Calmettes Marseille France
  More Information

No publications provided

Responsible Party: Innate Pharma
ClinicalTrials.gov Identifier: NCT01256073     History of Changes
Other Study ID Numbers: IPH 2101-102
Study First Received: December 7, 2010
Last Updated: February 27, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 27, 2014