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

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)

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.

Study Overview

• Status: Completed
• Conditions: Smoldering Multiple Myeloma
• Intervention / Treatment: Drug: IPH2101

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Innate Pharma
• Investigators: Principal Investigator: Nikhil Munshi, MD, Dana-Farber Cancer Institute- Medical Oncology- Boston MA-USA

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: October 8, 2010
• First Submitted That Met QC Criteria: October 15, 2010
• First Posted (Estimate): October 18, 2010

Study Record Updates

• Last Update Posted (Estimate): May 9, 2014
• Last Update Submitted That Met QC Criteria: April 11, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Smoldering Multiple Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Precancerous Conditions; Hypergammaglobulinemia; Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma
• Other Study ID Numbers: IPH2101-203