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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

Primary Purpose

Acute Myeloid Leukemia

Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
IPH2101
Sponsored by
Innate Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

60 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institut Paoli-Calmettes
  • Hopital Dupuytren
  • C.H.R.U. de Nantes - Hotel Dieu
  • Centre Hospitalier Lyon Sud - Hospices Civils de Lyon
  • Hopital de Purpan
  • Institut Gustave Roussy

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IPH2101

Arm Description

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

To assess the pharmacokinetics upon repeated dosing(s)of Anti-KIR(1-7F9)
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-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)
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

Full Information

First Posted
December 7, 2010
Last Updated
February 27, 2014
Sponsor
Innate Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT01256073
Brief Title
A Safety and Tolerability Extension Trial Assessing Repeated Dosing of Anti-KIR (1-7F9) Human Monoclonal Antibody in Patients With Acute Myeloid Leukaemia
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 Type
Interventional

2. Study Status

Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
February 2007 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Innate Pharma

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IPH2101
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
IPH2101
Intervention Description
IPH2101 fully human anti-KIR monoclonal antibody
Primary Outcome Measure Information:
Title
To assess safety and tolerability of repeating dosings of Anti-KIR(1-7F9)
Description
using the US National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE)
Time Frame
every 2 weeks
Secondary Outcome Measure Information:
Title
To assess the pharmacokinetics upon repeated dosing(s)of Anti-KIR(1-7F9)
Time Frame
every 2 weeks
Title
To assess the pharmacodynamics upon repeated dosing(s) of Anti-KIR(1-7F9)
Description
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
Time Frame
every 2 or 4 weeks
Title
To assess signs of efficacy of repeated dosing(s) with Anti-KIR(1-7F9)
Description
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
Time Frame
to date of progression diagnosed or until death

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) Acute myeloid leukaemia (AML) according to WHO Criteria 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 Life expectancy > 4 months as judged by the Investigator The patient is > or = 60 years of age but < or = 80 years of age 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 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 Recovery from acute toxicities of all previous anti-leukaemic therapies KIR-expression on patient NK-cells (ability to bind Anti-KIR(1-7F9)) if the patient did not participate in IPH2101-101 trial before ECOG performance status 0, 1 or 2 No major organ dysfunction as judged by the Investigator 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: Known or suspected allergy to trial product or related products Previous participation in this trial 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 Eligibility for allogeneic haematopoietic transplantation 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) The patient has received G-CSF treatment within the last 30 days prior to screening Systemic steroid treatment within the last 4 weeks prior to screening Patient has active autoimmune disease Diagnosis of monoclonal gammopathy Patient has active infectious disease Previous leukaemic CNS involvement Cardiac failure (New York Heart Association [NYHA] grade III-IV) Left ventricular ejection fraction (LVEF) less than 45 % of normal evaluated by ultrasound or isotopic evaluation Severe neurological/psychiatric disorder HIV or chronic hepatitis infection Clinical evidence of an active second malignancy Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation Any new medical condition that in the opinion of the Investigator disqualifies the patient for inclusion
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Norbert Vey, MD
Organizational Affiliation
Institut Paoli Calmettes Marseille France
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Paoli-Calmettes
City
Marseille
State/Province
Marseille Cedex 09
ZIP/Postal Code
13273
Country
France
Facility Name
Hopital Dupuytren
City
LIMOGES Cedex
ZIP/Postal Code
87042
Country
France
Facility Name
C.H.R.U. de Nantes - Hotel Dieu
City
NANTES Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Centre Hospitalier Lyon Sud - Hospices Civils de Lyon
City
Pierre-Bénite
ZIP/Postal Code
69495
Country
France
Facility Name
Hopital de Purpan
City
Toulouse Cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France

12. IPD Sharing Statement

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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

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