Clinical trial NCT01222286: Study on the Anti-tumor Activity, Safety and Pharmacology of IPH2101 in Patients With Smoldering Multiple Myeloma
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Smoldering Multiple Myeloma
Keywords: Smoldering Multiple Myeloma
Lead sponsor: Innate Pharma
Sponsor class: INDUSTRY
First posted: 2010-10-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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)
2. Measurable disease defined as a disease with a serum M protein ≥ 1 g/dl
3. No evidence of fatigue, recurrent infections or any clinical suspicion of MM
4. Diagnosis of SMM confirmed on two consecutive assessments (ie fluctuation under 25% of serum protein level) performed with at least a 4 week interval.
5. Age \> 18 years or \< 75 years
6. ECOG performance status of 0 or 1
7. 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
8. Informed consent signed by the patient

Exclusion Criteria:

1. 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.
2. Use of any investigational agent within the last 3 months
3. 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)
4. Primary or associated amyloidosis
5. 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
6. Current active infectious disease or positive serology for HIV, HCV or positive Hbs Antigen
7. History of or current auto-immune disease
8. History of other active malignancy within the past five years (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma).
9. Serious concurrent uncontrolled medical disorder
10. History of allograft or solid organ transplantation
11. Pregnant or lactating women
12. Any condition potentially hampering compliance with the study protocol and follow-up schedule

Primary outcomes:
measure: Rate of Patients Achieving an Objective Response
timeFrame: from start to end of study (14 months)
Secondary outcomes:
measure: Safety Assessment
timeFrame: Adverse events collected from screening visit (date of signature of Inform Consent Form) up to the End of Study, up to 14 months
measure: Pharmacodynamics of IPH2101
timeFrame: from start to end of study (14 months)
measure: Secondary Anti-tumor Activity
timeFrame: from start to end of study (14 months)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Dana-Farber Cancer Institute- Medical Oncology- Boston MA-USA
name: Nikhil Munshi, MD
role: PRINCIPAL_INVESTIGATOR
References: