Evaluation of Activity, Safety and Pharmacology of IPH2101 a Human Monoclonal Antibody in Patients With Multiple Myeloma (REMYKIR)
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
IPH2101
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- MM which initially required a systemic therapy and received a first line treatment, conventional doses of chemotherapies or high dose chemotherapy and an autologous transplantation of hematopoietic cells, followed or not by a consolidation treatment.
Residual disease considered as evaluable with:
- Quantifiable serum M-protein: ≥ 3 g/l, except for spike in the beta globulin area. In this particular case serum M-protein is considered quantifiable if ≥ 10g/l
- If serum M-protein is < 3g/l, measurable involved Free Light Chains ≥ 100 mg/l and an abnormal Free Light chains ratio (<0.26 or > 1.65)
Responses which are partial (PR and VGPR) and in plateau
- Partial response should meet the IMWG uniform response criteria: a ≥ 50% reduction from value of serum M-protein before the first line chemotherapy treatment and a reduction in 24h urinary M-protein by ≥ 90% or to < 200 mg /24h;
- Very good partial response according to the IMWG uniform response criteria with 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg/24h; furthermore the M-protein should spike in the gamma globulin area;
Plateau phase is defined by :
- For patients with serum M-protein ≥ 3g/l: stable levels of M-protein in serum during at least 2 months checked on at least 3 consecutive samples, with the third evaluation performed within 4 weeks before study entry. Fluctuations of ± 25 % and ± 2 g/l in Serum M-protein levels are allowed.
- For Patients with serum M-protein < 3g/l: stable levels Free Light Chains in serum during at least 2 months checked on at least 3 consecutive samples, with the third evaluation performed within 4 weeks before study entry. Fluctuations of ± 25 % of involved serum Free Light Chain are allowed.
- ECOG performance status of 0, 1 or 2.
Clinical laboratory values at screening:
- Calculated creatinine clearance (according to MDRD) > 50 ml/min
- Platelet > 50 x 109 /l
- ANC > 1 x 109 /l
- Bilirubin levels < 1.5 ULN; ALT and AST < 2.5 ULN
- Male or female patient who accepts and is able to use recognised effective contraception (oral contraceptives, IUCD, barrier method of contraception in conjunction with spermicidal jelly) throughout the study.
- Signed inform consent obtained before any trial-related activities
Exclusion Criteria:
- Age < 18 years old or > 75 years old
- Previous consolidation/ maintenance therapy by Imid (thalidomide, lenalidomid) or bortezomib within the last 2 months
- Treatment with chemotherapy, systemic corticosteroid within the previous 2 months
- Treatment with growth factors (EPO, G- or GM-CSF) within the previous 1 month
- Radiotherapy for bone or visceral lesion within the last 3 months
- Use of any investigational agent within the last 2 months
- Primary or associated amyloidosis
- Peripheral neuropathy of grade ≥ III according to the CTCAE of the NCI
Abnormal cardiac status with any of the following
- NYHA stage III or IV congestive heart failure
- myocardial infarction within the previous 6 months
- symptomatic cardiac arrhythmia despite treatment
- Current active infectious disease or positive serology for HIV, HCV or positive Hbs Antigen
- History of or current auto-immune disease
- Serious concurrent uncontrolled medical disorder
- History of other malignancy for less then 5 years (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma)
- History of allogenic hematopoietic cell or solid organ transplantation
- Pregnant or lactating women
- Any medical condition which is regarded by the investigator as incompatible with the study participation
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Sites / Locations
- C.H.R.U. de Caen - Hôpital Bretonneau
- CHU Dijon
- CHRU Lille
- Hôpital Dupuytren
- Institut Paoli Calmettes
- CHU Nancy
- Hopital Saint Louis
- Hôpital Saint Antoine
- C.H.R.U. de Tours
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
IPH 2101 0.2 mg/kg
IPH2101 2.0 mg/kg
Arm Description
One infusion of IPH2101 every 4 weeks at the dose of 0.2 mg/kg by intravenous route over 1 hour, for 4 or up to 8 cycles.
One infusion of IPH2101 every 4 weeks at the dose of 2 mg/kg by intravenous route over 1 hour, for 4 or up to 8 cycles.
Outcomes
Primary Outcome Measures
Rate of Patients Achieving a Response Based on M-protein or Free Light Chains
Response was defined:
In patients with a serum M-protein > 5 g/l, as a reduction of at least 25% (minor response according to European society for Blood and Marrow Transplantation (EBMT)) from baseline of serum M-protein confirmed on two consecutive determinations at 4 weeks interval;
In patients with a serum M-protein ≤ 5 g/l and ≥ 3g/l, as a negative electrophoresis
In patients with serum M-protein < 3 g/l but a measurable involved serum free light chains ≥ 100 mg/l and an abnormal Free Light Chains ratio (<0.26 or > 1.65), as a ≥ 50 % decrease in the difference between involved and uninvolved Free Light Chains levels.
Secondary Outcome Measures
Biological Activity of IPH2101 on Killer Immunogloblin Like Receptors (KIR) Occupancy at End of Treatment
KIR-occupancy is a relative measure of the fraction of cell surface KIR that is occupied by the IPH2101 monoclonal antibody, and hence is unavailable for binding to HLA ligands.
Safety Assessment
Adverse Events, Serious Adverse Events, physical examination and biological changes.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00999830
Brief Title
Evaluation of Activity, Safety and Pharmacology of IPH2101 a Human Monoclonal Antibody in Patients With Multiple Myeloma
Acronym
REMYKIR
Official Title
Randomised Phase II Study Evaluating the Anti-tumour Activity, Safety and Pharmacology of Two Dose Regimens of IPH2101, a Human Monoclonal Anti-KIR Antibody, in Patients With Multiple Myeloma in Stable Partial Response After a First Line Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
June 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Innate Pharma
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open randomised phase II study evaluating the anti-tumour activity, safety and pharmacology of two dose regimens of IPH2101, a human monoclonal anti-KIR antibody, in patients with multiple myeloma in stable partial response after a first line therapy.
Detailed Description
Development of new treatments for diseases such as multiple myeloma is a focus for research. The research being conducted is on treatment called Anti-KIR, which activates the body's own cells to kill tumor cells. This is different from many other treatments where chemicals are given to kill tumor cells.The primary objective of the study is to evaluate the clinical activity of two different dose regimens (0.2 mg/kg, leading to an intermittent saturation of NK receptors and 2mg/kg leading to a sustained saturation of NK receptors) of IPH2101 administered as a single agent in multiple myeloma patients who achieved, after the completion of any first line treatment, including conventional or high dose chemotherapies, a stable partial or very good partial response (PR or VGPR).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IPH 2101 0.2 mg/kg
Arm Type
Experimental
Arm Description
One infusion of IPH2101 every 4 weeks at the dose of 0.2 mg/kg by intravenous route over 1 hour, for 4 or up to 8 cycles.
Arm Title
IPH2101 2.0 mg/kg
Arm Type
Experimental
Arm Description
One infusion of IPH2101 every 4 weeks at the dose of 2 mg/kg by intravenous route over 1 hour, for 4 or up to 8 cycles.
Intervention Type
Drug
Intervention Name(s)
IPH2101
Other Intervention Name(s)
Fully human anti-KIR monoclonal antibody (1-7F9)
Intervention Description
One infusion of IPH2101 every 4 weeks
Primary Outcome Measure Information:
Title
Rate of Patients Achieving a Response Based on M-protein or Free Light Chains
Description
Response was defined:
In patients with a serum M-protein > 5 g/l, as a reduction of at least 25% (minor response according to European society for Blood and Marrow Transplantation (EBMT)) from baseline of serum M-protein confirmed on two consecutive determinations at 4 weeks interval;
In patients with a serum M-protein ≤ 5 g/l and ≥ 3g/l, as a negative electrophoresis
In patients with serum M-protein < 3 g/l but a measurable involved serum free light chains ≥ 100 mg/l and an abnormal Free Light Chains ratio (<0.26 or > 1.65), as a ≥ 50 % decrease in the difference between involved and uninvolved Free Light Chains levels.
Time Frame
From the start of the treatment to the End of Study and during the post study follow up during 2 years according to standard practices
Secondary Outcome Measure Information:
Title
Biological Activity of IPH2101 on Killer Immunogloblin Like Receptors (KIR) Occupancy at End of Treatment
Description
KIR-occupancy is a relative measure of the fraction of cell surface KIR that is occupied by the IPH2101 monoclonal antibody, and hence is unavailable for binding to HLA ligands.
Time Frame
From the start up to the end of study (15 months)
Title
Safety Assessment
Description
Adverse Events, Serious Adverse Events, physical examination and biological changes.
Time Frame
from screening visit to the End of Study (at each study visit)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
MM which initially required a systemic therapy and received a first line treatment, conventional doses of chemotherapies or high dose chemotherapy and an autologous transplantation of hematopoietic cells, followed or not by a consolidation treatment.
Residual disease considered as evaluable with:
Quantifiable serum M-protein: ≥ 3 g/l, except for spike in the beta globulin area. In this particular case serum M-protein is considered quantifiable if ≥ 10g/l
If serum M-protein is < 3g/l, measurable involved Free Light Chains ≥ 100 mg/l and an abnormal Free Light chains ratio (<0.26 or > 1.65)
Responses which are partial (PR and VGPR) and in plateau
Partial response should meet the IMWG uniform response criteria: a ≥ 50% reduction from value of serum M-protein before the first line chemotherapy treatment and a reduction in 24h urinary M-protein by ≥ 90% or to < 200 mg /24h;
Very good partial response according to the IMWG uniform response criteria with 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg/24h; furthermore the M-protein should spike in the gamma globulin area;
Plateau phase is defined by :
For patients with serum M-protein ≥ 3g/l: stable levels of M-protein in serum during at least 2 months checked on at least 3 consecutive samples, with the third evaluation performed within 4 weeks before study entry. Fluctuations of ± 25 % and ± 2 g/l in Serum M-protein levels are allowed.
For Patients with serum M-protein < 3g/l: stable levels Free Light Chains in serum during at least 2 months checked on at least 3 consecutive samples, with the third evaluation performed within 4 weeks before study entry. Fluctuations of ± 25 % of involved serum Free Light Chain are allowed.
ECOG performance status of 0, 1 or 2.
Clinical laboratory values at screening:
Calculated creatinine clearance (according to MDRD) > 50 ml/min
Platelet > 50 x 109 /l
ANC > 1 x 109 /l
Bilirubin levels < 1.5 ULN; ALT and AST < 2.5 ULN
Male or female patient who accepts and is able to use recognised effective contraception (oral contraceptives, IUCD, barrier method of contraception in conjunction with spermicidal jelly) throughout the study.
Signed inform consent obtained before any trial-related activities
Exclusion Criteria:
Age < 18 years old or > 75 years old
Previous consolidation/ maintenance therapy by Imid (thalidomide, lenalidomid) or bortezomib within the last 2 months
Treatment with chemotherapy, systemic corticosteroid within the previous 2 months
Treatment with growth factors (EPO, G- or GM-CSF) within the previous 1 month
Radiotherapy for bone or visceral lesion within the last 3 months
Use of any investigational agent within the last 2 months
Primary or associated amyloidosis
Peripheral neuropathy of grade ≥ III according to the CTCAE of the NCI
Abnormal cardiac status with any of the following
NYHA stage III or IV congestive heart failure
myocardial infarction within the previous 6 months
symptomatic cardiac arrhythmia despite treatment
Current active infectious disease or positive serology for HIV, HCV or positive Hbs Antigen
History of or current auto-immune disease
Serious concurrent uncontrolled medical disorder
History of other malignancy for less then 5 years (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma)
History of allogenic hematopoietic cell or solid organ transplantation
Pregnant or lactating women
Any medical condition which is regarded by the investigator as incompatible with the study participation
Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michel ATTAL, MD
Organizational Affiliation
CHU Toulouse
Official's Role
Principal Investigator
Facility Information:
Facility Name
C.H.R.U. de Caen - Hôpital Bretonneau
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
CHU Dijon
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
CHRU Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hôpital Dupuytren
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
Institut Paoli Calmettes
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
CHU Nancy
City
Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Hopital Saint Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Hôpital Saint Antoine
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
C.H.R.U. de Tours
City
Tours
ZIP/Postal Code
37044
Country
France
12. IPD Sharing Statement
Learn more about this trial
Evaluation of Activity, Safety and Pharmacology of IPH2101 a Human Monoclonal Antibody in Patients With Multiple Myeloma
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