Study on the Safety, Anti-tumor Activity and Pharmacology of IPH2101 Combined With Lenalidomide in Patients With Multiple Myeloma Experiencing a First or Second Relapse (KIRIMID)
Primary Purpose
Patients With Multiple Myeloma Experiencing a, First or Second Relapse
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
IPH2101 combined to lenalidomide
Sponsored by
About this trial
This is an interventional treatment trial for Patients With Multiple Myeloma Experiencing a
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent obtained before any trial-related activities
- Progressive disease or relapse of multiple myeloma (according to the IMWG definition) after one or two prior therapeutic treatments or regimens for multiple myeloma that achieved a response duration of at least 6 months
- Prior therapeutic treatment regimens may have included Thalidomide and Lenalidomide. Regarding patients previously treated by Lenalidomide, only patients who achieved at least Partial Response duration of at least 6 months can be included. The patient must not have discontinued treatment due to Lenalidomide intolerance.
Measurable disease, as indicated by one or more of the following:
- Serum M-protein ≥ 0.5 g/dL If Serum Protein Electrophoresis is felt to be unreliable for routine M-protein measurement (particularly for patients with IgA MM), then quantitative immunoglobulin levels can be accepted).
- Urine Bence-Jones protein ≥ 200 mg/24 h
- Involved serum Free Light Chains (sFLC) level ≥ 10 mg/dl ( ≥ 100 mg/l) provided sFLC ratio is abnormal (<0.26 or >1.65)
- ECOG performance status of 0, 1 or 2
Clinical laboratory values at screening
- Calculated creatinine clearance (according to MDRD) > 60 ml/min
- Platelet ≥ 75 x 109 /l for patients with < 50% BM plasma cells, and ≥ 30 x 109 /l for patients with > 50% BM plasma cells
- ANC > 1 x 109 /l
- Bilirubin levels < 1.5 ULN ; ALT and AST < 3 ULN (grade 1 NCI)
- Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing Lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking Lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
- All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
Exclusion Criteria:
- Age < 18 years or > 80 years
- Non secreting multiple myeloma or non measurable disease (< 0.5 g /dL M-Protein in serum or < 200 mg urinary M-protein / 24 h or <10 mg/dl involved sFLC)
- Life-threatening conditions related or not to MM relapse
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking Lenalidomide)
- Known hypersensitivity to thalidomide or IMiD®.
- Use of any investigational agent within the last month
- Treatment by systemic corticosteroids (except inhaled corticosteroids) or chemotherapy (including consolidation and maintenance) within the last month (use of biphosphonates is permitted)
- Radiotherapy within the last month
- Primary or associated amyloidosis
- Peripheral neuropathy of grade ≥ 3 according to the CTCAE of the NCI
Abnormal cardiac status with any of the following
- NYHA stage III or IV congestive heart failure
- myocardial infarction within the previous 6 months
- cardiac arrhythmia remaining symptomatic despite 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 5 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
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Inability to comply with an antithrombotic regimen
Sites / Locations
- Dana Farber
- NYU Clinical Cancer Center
- Mount Sinai Medical Center
- The Ohio State University Comprehensive Cancer Center
- Fox Chase Cancer Center
- Saint Francis Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
IPH2101 and lenalinomide
Arm Description
Outcomes
Primary Outcome Measures
number of patients with Dose Limiting Toxicity (DLT) at each dose level
safety of IPH2101 combined with lenalidomide at different dose levels.
Secondary Outcome Measures
To assess response rate of the combination
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01217203
Brief Title
Study on the Safety, Anti-tumor Activity and Pharmacology of IPH2101 Combined With Lenalidomide in Patients With Multiple Myeloma Experiencing a First or Second Relapse
Acronym
KIRIMID
Official Title
Multicenter Phase I Study on the Safety, Anti-tumor Activity and Pharmacology of IPH2101, a Human Monoclonal Anti-KIR, Combined With Lenalidomide in Patients With Multiple Myeloma Experiencing a First or Second Relapse
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
September 2010 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
February 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Innate Pharma
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of the clinical study is to evaluate, in patients who experience a first or second relapse of their multiple myeloma, the safety of escalating doses of IPH2101 combined with lenalidomide
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patients With Multiple Myeloma Experiencing a, First or Second Relapse
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IPH2101 and lenalinomide
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
IPH2101 combined to lenalidomide
Intervention Description
Dose level 1 : 0.2 mg/kg IPH2101(with Lenalidomide 10 mg/day) Dose level 2 : 0.2 mg/kg IPH2101(with Lenalidomide 25 mg/day) Dose level 3 : 1 mg/kg IPH2101(with Lenalidomide 25 mg/day) Dose level 4 : 2 mg/kg IPH2101(with Lenalidomide 25 mg/day)
Extension cohort: 6 patients at the Maximum Tolerated Dose (MTD)
Primary Outcome Measure Information:
Title
number of patients with Dose Limiting Toxicity (DLT) at each dose level
Description
safety of IPH2101 combined with lenalidomide at different dose levels.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
To assess response rate of the combination
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent obtained before any trial-related activities
Progressive disease or relapse of multiple myeloma (according to the IMWG definition) after one or two prior therapeutic treatments or regimens for multiple myeloma that achieved a response duration of at least 6 months
Prior therapeutic treatment regimens may have included Thalidomide and Lenalidomide. Regarding patients previously treated by Lenalidomide, only patients who achieved at least Partial Response duration of at least 6 months can be included. The patient must not have discontinued treatment due to Lenalidomide intolerance.
Measurable disease, as indicated by one or more of the following:
Serum M-protein ≥ 0.5 g/dL If Serum Protein Electrophoresis is felt to be unreliable for routine M-protein measurement (particularly for patients with IgA MM), then quantitative immunoglobulin levels can be accepted).
Urine Bence-Jones protein ≥ 200 mg/24 h
Involved serum Free Light Chains (sFLC) level ≥ 10 mg/dl ( ≥ 100 mg/l) provided sFLC ratio is abnormal (<0.26 or >1.65)
ECOG performance status of 0, 1 or 2
Clinical laboratory values at screening
Calculated creatinine clearance (according to MDRD) > 60 ml/min
Platelet ≥ 75 x 109 /l for patients with < 50% BM plasma cells, and ≥ 30 x 109 /l for patients with > 50% BM plasma cells
ANC > 1 x 109 /l
Bilirubin levels < 1.5 ULN ; ALT and AST < 3 ULN (grade 1 NCI)
Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing Lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking Lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
Exclusion Criteria:
Age < 18 years or > 80 years
Non secreting multiple myeloma or non measurable disease (< 0.5 g /dL M-Protein in serum or < 200 mg urinary M-protein / 24 h or <10 mg/dl involved sFLC)
Life-threatening conditions related or not to MM relapse
Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking Lenalidomide)
Known hypersensitivity to thalidomide or IMiD®.
Use of any investigational agent within the last month
Treatment by systemic corticosteroids (except inhaled corticosteroids) or chemotherapy (including consolidation and maintenance) within the last month (use of biphosphonates is permitted)
Radiotherapy within the last month
Primary or associated amyloidosis
Peripheral neuropathy of grade ≥ 3 according to the CTCAE of the NCI
Abnormal cardiac status with any of the following
NYHA stage III or IV congestive heart failure
myocardial infarction within the previous 6 months
cardiac arrhythmia remaining symptomatic despite 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 5 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
Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Inability to comply with an antithrombotic regimen
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Don Benson, MD
Organizational Affiliation
The Ohio State University Comprehensive Cancer Center - Columbus OH - USA
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana Farber
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
NYU Clinical Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
The Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Saint Francis Hospital
City
Greensville
State/Province
South Carolina
ZIP/Postal Code
29601
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
25999435
Citation
Benson DM Jr, Cohen AD, Jagannath S, Munshi NC, Spitzer G, Hofmeister CC, Efebera YA, Andre P, Zerbib R, Caligiuri MA. A Phase I Trial of the Anti-KIR Antibody IPH2101 and Lenalidomide in Patients with Relapsed/Refractory Multiple Myeloma. Clin Cancer Res. 2015 Sep 15;21(18):4055-61. doi: 10.1158/1078-0432.CCR-15-0304. Epub 2015 May 21.
Results Reference
derived
Learn more about this trial
Study on the Safety, Anti-tumor Activity and Pharmacology of IPH2101 Combined With Lenalidomide in Patients With Multiple Myeloma Experiencing a First or Second Relapse
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