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

Phase 2

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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
1. NYHA stage III or IV congestive heart failure
2. myocardial infarction within the previous 6 months
3. 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

Arm && Interventions

Group	Intervention	Description
IPH2101 0.2 mg/kg	IPH2101	0.2 mg/Kg every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles
IPH2101 2 mg/kg	IPH2101	2 mg/Kg every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles

Primary Outcome Measures

Name	Time	Method
Rate of Patients Achieving an Objective Response	from start to end of study (14 months)	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.

Secondary Outcome Measures

Name	Time	Method
Safety Assessment	Adverse events collected from screening visit (date of signature of Inform Consent Form) up to the End of Study, up to 14 months	adverse events, physical examination and biological changes during the whole clinical trial.
Pharmacodynamics of IPH2101	from start to end of study (14 months)	biological activity of IPH2101 on KIR occupancy at End of Treatment
Secondary Anti-tumor Activity	from start to end of study (14 months)	* 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

Locations (5): Sarah Cannon Research Institute
🇺🇸
Nashville, Tennessee, United States
Ohio State University
🇺🇸
Columbus, Ohio, United States
Dana-Farber Cancer Institute
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Boston, Massachusetts, United States
Mount Sinai School of Medicine
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New York, New York, United States
Hospital of the University of Pennsylvania
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Philadelphia, Pennsylvania, United States