Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Evaluation of Activity, Safety and Pharmacology of IPH2101 a Human Monoclonal Antibody in Patients With Multiple Myeloma (REMYKIR)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Innate Pharma
ClinicalTrials.gov Identifier:
NCT00999830
First received: October 21, 2009
Last updated: February 23, 2016
Last verified: April 2014

October 21, 2009
February 23, 2016
September 2009
June 2012   (final data collection date for primary outcome measure)
Rate of Patients Achieving a Response Based on M-protein or Free Light Chains [ 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 ] [ Designated as safety issue: No ]

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.
M-protein will be measured in serum at Screening and every 4 weeks during the study period from Cycle1-day1 to End of Study [ Time Frame: every 4 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00999830 on ClinicalTrials.gov Archive Site
  • Biological Activity of IPH2101 on Killer Immunogloblin Like Receptors (KIR) Occupancy at End of Treatment [ Time Frame: From the start up to the end of study (15 months) ] [ Designated as safety issue: No ]
    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 [ Time Frame: from screening visit to the End of Study (at each study visit) ] [ Designated as safety issue: No ]
    Adverse Events, Serious Adverse Events, physical examination and biological changes.
  • To assess pharmacokinetic (PK) parameters of Anti-KIR [ Time Frame: every 4 weeks ] [ Designated as safety issue: No ]
  • To assess pharmacodynamic parameters of Anti-KIR [ Time Frame: every 4 weeks ] [ Designated as safety issue: No ]
  • To assess Safety of 2 dose regimens of Anti-Kir [ Time Frame: every 4 weeks ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Evaluation of Activity, Safety and Pharmacology of IPH2101 a Human Monoclonal Antibody in Patients With Multiple Myeloma
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
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.
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).
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
Drug: IPH2101
One infusion of IPH2101 every 4 weeks
Other Name: Fully human anti-KIR monoclonal antibody (1-7F9)
  • Experimental: IPH 2101 0.2 mg/kg
    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.
    Intervention: Drug: IPH2101
  • Experimental: IPH2101 2.0 mg/kg
    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: Drug: IPH2101
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
27
June 2013
June 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. 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.
  2. 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)
  3. 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.
  4. ECOG performance status of 0, 1 or 2.
  5. 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
  6. 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.
  7. Signed inform consent obtained before any trial-related activities

Exclusion Criteria:

  1. Age < 18 years old or > 75 years old
  2. Previous consolidation/ maintenance therapy by Imid (thalidomide, lenalidomid) or bortezomib within the last 2 months
  3. Treatment with chemotherapy, systemic corticosteroid within the previous 2 months
  4. Treatment with growth factors (EPO, G- or GM-CSF) within the previous 1 month
  5. Radiotherapy for bone or visceral lesion within the last 3 months
  6. Use of any investigational agent within the last 2 months
  7. Primary or associated amyloidosis
  8. Peripheral neuropathy of grade ≥ III according to the CTCAE of the NCI
  9. Abnormal cardiac status with any of the following

    1. NYHA stage III or IV congestive heart failure
    2. myocardial infarction within the previous 6 months
    3. symptomatic cardiac arrhythmia despite treatment
  10. Current active infectious disease or positive serology for HIV, HCV or positive Hbs Antigen
  11. History of or current auto-immune disease
  12. Serious concurrent uncontrolled medical disorder
  13. History of other malignancy for less then 5 years (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma)
  14. History of allogenic hematopoietic cell or solid organ transplantation
  15. Pregnant or lactating women
  16. Any medical condition which is regarded by the investigator as incompatible with the study participation
  17. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Both
18 Years to 75 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00999830
IPH2101-201
Yes
Not Provided
Not Provided
Innate Pharma
Innate Pharma
Not Provided
Principal Investigator: Michel ATTAL, MD CHU Toulouse
Innate Pharma
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP