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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Innate Pharma
ClinicalTrials.gov Identifier:
NCT01222286
First received: October 8, 2010
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Smoldering Multiple Myeloma
Drug: IPH2101
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Innate Pharma:

Primary Outcome Measures:
  • Rate of Patients Achieving an Objective Response [ Time Frame: from start to end of study (14 months) ] [ Designated as safety issue: No ]
    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:
  • Safety Assessment [ Time Frame: Adverse events collected from screening visit (date of signature of Inform Consent Form) up to the End of Study, up to 14 months ] [ Designated as safety issue: Yes ]
    adverse events, physical examination and biological changes during the whole clinical trial.

  • Pharmacodynamics of IPH2101 [ Time Frame: from start to end of study (14 months) ] [ Designated as safety issue: No ]
    biological activity of IPH2101 on KIR occupancy at End of Treatment

  • Secondary Anti-tumor Activity [ Time Frame: from start to end of study (14 months) ] [ Designated as safety issue: No ]
    • 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


Enrollment: 30
Study Start Date: September 2010
Study Completion Date: January 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: a human monoclonal anti-KIR antibody (1-7F9)

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01222286

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Innate Pharma
Investigators
Principal Investigator: Nikhil Munshi, MD Dana-Farber Cancer Institute- Medical Oncology- Boston MA-USA
  More Information

No publications provided

Responsible Party: Innate Pharma
ClinicalTrials.gov Identifier: NCT01222286     History of Changes
Obsolete Identifiers: NCT01960959
Other Study ID Numbers: IPH2101-203
Study First Received: October 8, 2010
Results First Received: November 7, 2013
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Innate Pharma:
Smoldering Multiple Myeloma

Additional relevant MeSH terms:
Pharmacologic Actions
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2014