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

Primary Purpose

Smoldering Multiple Myeloma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

IPH2101

About this trial

This is an interventional treatment trial for Smoldering Multiple Myeloma focused on measuring Smoldering Multiple Myeloma

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Dana-Farber Cancer Institute
Mount Sinai School of Medicine
Ohio State University
Hospital of the University of Pennsylvania
Sarah Cannon Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

IPH2101 0.2 mg/kg

IPH2101 2 mg/kg

Arm Description

0.2 mg/Kg every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles

2 mg/Kg every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Safety Assessment

adverse events, physical examination and biological changes during the whole clinical trial.

Pharmacodynamics of IPH2101

biological activity of IPH2101 on KIR occupancy at End of Treatment

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

Full Information

NCT ID

NCT01222286

First Posted

October 8, 2010

Last Updated

April 11, 2014

Sponsor

Innate Pharma

1. Study Identification

Unique Protocol Identification Number

NCT01222286

Brief Title

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

Acronym

KIRMONO

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

2. Study Status

Record Verification Date

April 2014

Overall Recruitment Status

Completed

Study Start Date

September 2010 (undefined)

Primary Completion Date

July 2012 (Actual)

Study Completion Date

January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Innate Pharma

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Smoldering Multiple Myeloma

Keywords

Smoldering Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

IPH2101 0.2 mg/kg

Arm Type

Experimental

Arm Description

0.2 mg/Kg every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles

Arm Title

IPH2101 2 mg/kg

Arm Type

Experimental

Arm Description

2 mg/Kg every 4 weeks by intravenous route over 1 hour, for 6 or up to 12 cycles

Intervention Type

Drug

Intervention Name(s)

IPH2101

Other Intervention Name(s)

a human monoclonal anti-KIR antibody (1-7F9)

Intervention Description

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

Primary Outcome Measure Information:

Title

Rate of Patients Achieving an Objective Response

Description

Time Frame

from start to end of study (14 months)

Secondary Outcome Measure Information:

Title

Safety Assessment

Description

adverse events, physical examination and biological changes during the whole clinical trial.

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

Title

Pharmacodynamics of IPH2101

Description

biological activity of IPH2101 on KIR occupancy at End of Treatment

Time Frame

from start to end of study (14 months)

Title

Secondary Anti-tumor Activity

Description

Time Frame

from start to end of study (14 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nikhil Munshi, MD

Organizational Affiliation

Dana-Farber Cancer Institute- Medical Oncology- Boston MA-USA

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dana-Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Mount Sinai School of Medicine

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

Ohio State University

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Facility Name

Hospital of the University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Sarah Cannon Research Institute

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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