Study on the Anti-tumor Activity, Safety and Pharmacology of IPH2101 in Patients With Smoldering Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the anti-tumor activity, safety and pharmacology of two dose regimens (0.2 and 2 mg/kg)of IPH2101 in patients with Smoldering Multiple Myeloma.

Detailed Description
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This is a randomized Phase II, open label, multi-centre study, with two independent arms. Patients receive 6 injections of IPH2101, at the dose of 0.2 mg/kg or 2 mg/kg (according to their randomization) administered over one hour infusion at four weeks intervals. A patient whose disease achieves at least a minimal response to study treatment at any time during the initial period of 6 cycles can be treated with an additional period of treatment of 6 cycles. Patients are followed 6 months after treatment completion or until a KIR occupancy level < 30% (i.e if the time required for KIR desaturation was > 6 months), whichever is longer.

Official Title
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Multicenter Phase II Study on the Anti-tumor Activity, Safety and Pharmacology of Two Dose Regimens of IPH2101, a Fully Human Monoclonal Anti KIR Antibody, in Patients With Smoldering Multiple Myeloma (KIRMONO)

Conditions
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Smoldering Multiple Myeloma

Intervention / Treatment
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* Drug: IPH2101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SMM of any risk level according to a definition derived of the International Myeloma Working Group definition ( Br J Haematol 2003; 121: 749) : Serum M protein ≥ 3 g/dl , AND/OR Bone Marrow plasma cells ≥ 10 % with no evidence of end-organ damage (CRAB) (C)Absence of hypercalcemia : Ca < 10.5 mg/dl (R)Absence of renal failure : creatinine < 2mg/dl (177 μmol/l) or calculated creatinine clearance(according to MDRD) > 50 ml/min (A)Absence of anemia : Hb > 11 g/dl (B)Absence of lytic bone lesion on standard skeletal survey (MRI could be used if clinically indicated) Measurable disease defined as a disease with a serum M protein ≥ 1 g/dl No evidence of fatigue, recurrent infections or any clinical suspicion of MM Diagnosis of SMM confirmed on two consecutive assessments (ie fluctuation under 25% of serum protein level) performed with at least a 4 week interval. Age > 18 years or < 75 years ECOG performance status of 0 or 1 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 when relevant Informed consent signed by the patient Exclusion Criteria: Previous treatment having a proven or potential impact on myelomatous cells proliferation or survival (including IMiDs or proteasome inhibitors, conventional chemotherapies within the last 5 years, steroids within the last month prior to enrolment). Previous bisphosphonates started less than 3 months prior to enrolment. Use of any investigational agent within the last 3 months Clinical laboratory values at screening Platelet < 75 x 10^9 /l ANC < 1.5 x 10^9 /l Bilirubin levels >1.5 ULN ; ALT and AST > 3 ULN (grade 1 NCI) Primary or associated amyloidosis 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 requiring treatment or persisting despite appropriate treatment Current active infectious disease or positive serology for HIV, HCV or positive Hbs Antigen History of or current auto-immune disease History of other active malignancy within the past five years (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma). Serious concurrent uncontrolled medical disorder History of allograft or solid organ transplantation Pregnant or lactating women Any condition potentially hampering compliance with the study protocol and follow-up schedule

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPH2101 0.2 mg/kg<br>0.2 mg/Kg every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles | Drug: IPH2101<br>* 0.2 mg/Kg or 2mg/Kg, every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles<br>* Other names: a human monoclonal anti-KIR antibody (1-7F9);|
| Experimental: IPH2101 2 mg/kg<br>2 mg/Kg every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles | Drug: IPH2101<br>* 0.2 mg/Kg or 2mg/Kg, every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles<br>* Other names: a human monoclonal anti-KIR antibody (1-7F9);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Patients Achieving an Objective Response | The primary end point is the rate of patients achieving an objective response (defined according to the International Myeloma Working Group uniform response criteria), including minimal response, (as derived from the European Society for Blood and Marrow Transplantation criteria), achieved at any time until end of study and confirmed on two consecutive assessments at 4 weeks interval. | from start to end of study (14 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Assessment | adverse events, physical examination and biological changes during the whole clinical trial. | Adverse events collected from screening visit (date of signature of Inform Consent Form) up to the End of Study, up to 14 months | 
| Pharmacodynamics of IPH2101 | biological activity of IPH2101 on KIR occupancy at End of Treatment | from start to end of study (14 months) | 
| Secondary Anti-tumor Activity | any change of M-protein in serum occurring during the study (>25 percentage increase in level of serum M-protein) progression to active Multiple Myeloma Definition of active Multiple Myeloma: Evidence of progression based on the IMWG criteria for progressive disease in myeloma and any one or more of the following felt related to the underlying clonal plasma cell proliferative disorder : Development of new soft tissue plasmacytomas or bone lesions Hypercalcemia (> 11mg/100ml) Decrease in hemoglobin of > 2g/100ml Rise in serum creatinine by 2 mg/100ml or more | from start to end of study (14 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoldering Multiple Myeloma