Back to resultsA Study of KW-2478 in Combination With Bortezomib in Subjects With Relapsed and/or Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
KW-2478
Bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Leukemia, Immunoproliferative Disorder, Neoplasma by Histologic Type, Immune System Diseases, Hematologic Diseases, Blood Protein Disorders, Paraproteinemias, Multiple Myeloma, Hematologic Disorders, Leukemia, Chronic, B-cell, Leukemia, B-cell, Leukemia, Chronic, Neoplasms, Plasma Cell, Monoclonal Gammopathy of unknown significance (MGUS)
Eligibility Criteria
Accepts Healthy Volunteers: No
Inclusion Criteria:
- Subjects with a confirmed diagnosis of Multiple Myeloma who have had one and no more than three prior regimens for MM to which they did not respond (failed) or from which they have relapsed.
- Signed either an IRB or IEC approved informed consent
- ECOG performance status of ≤ 2
- Life expectancy of at least 3 months
- M protein in either serum or urine, or free light chains if not measurable M protein in serum or urine, and clonal bone marrow plasma cells > 10%, and evidence of end organ damage
- Adequate hematologic status, liver and renal function
- Subjects of reproductive potential must agree to follow accepted pregnancy prevention methods during the study.
Exclusion Criteria:
- No anti-cancer treatment for ≥ 4 weeks and no bortezomib treatment ≥ 60 days prior to receiving study drug
- Any other severe, acute or chronic illness
- No other prior or concurrent malignancy
- No immunosuppressant therapy
Sites / Locations
- Arizona Clinical Research Center, Inc. / Arizona Oncology Associates, 1825 N Kolb,
- Pacific Shores Medical Group 1043 Elm Ave, Suite 104
- UCLA Medical Center Hematology / Oncology Division, 10945 Le Conte Ave #2333,
- Collaborative Research Group 2320 S Seacrest Blvd, Suite 202
- Rush University Medical Center / Division of Hematology/Oncology Research 1725 W Harrison Street, Suite 834
- Cancer Institute of New Jersey 195 Little Albany Street
- The Jones Clinic 7710 Wolf River Circle
- UT MD Anderson Cancer Center, 1515 Holcombe Boulevard,
- Gundersen Clinic Center for Cancer and Blood Disorders, 1900 South Ave, EB2-001,
- National Kidney and Transplant Institute, Rm 3215 Doctors Clinic, East Avenue
- Makati Medical Center, New Wing Hall C372, #2 Amorsolo Street, Legaspi Village,
- The Medical City, 1609 MATI Building, The Medical City, Ortigas Avenue,
- Saint Lukes Medical Center, Rm 222 MAB Saint Lukes Medical Center, E. Rodriguez
- Darent Valley Hospital Dept of Haematology, Acorn House, Darenth Wood Road
- St Bartholomew's Hospital Haematology Department, 1st Floor, Pathology
- Christie Hospital - Department Haematology, 550 Wilmslow Road
- Hillingdon Hospital Dept of Haematology, Pield Health Road
- Nottingham University Hospitals NHS Trust, Centre for Clinical Haemotology
- Royal Marsden Hospital, Orchard House
- Royal Bournemouth Hospital, Dept. of Haematolgy, Castle Lane East,
- Royal Devon & Exeter Hospital Haematology Centre, Barrack Road
- Northwick Park Hospital Dept of Haematology, Watford Road
- St James Hospital, St James' Institute of Oncology, Department of Haematology, Level 03, Bexley Wing,
- UCL Cancer Institute, Paul O'Gorman Building, University College London,72 Huntley Street
- Manchester Royal Infirmary Dept of Haematology, Oxford Road
- Royal Cornwall Hospital Haematology Clinic
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Phase 1: Cohort 1
Phase 1: Cohort 2
Phase 1: Cohort 3
Phase 1: Cohort 4
Phase 2
Arm Description
Cohort 1: KW 2478 130 mg/m^2 and Bortezomib 1.0 mg/m^2
Cohort 2: KW 2478 130 mg/m^2 and Bortezomib 1.3 mg/m^2
Cohort 3: KW 2478 175 mg/m^2 and Bortezomib 1.0 mg/m^2
Cohort 4: KW 2478 175 mg/m^2 and Bortezomib 1.3 mg/m^2
KW 2478 175 mg/m^2 and Bortezomib 1.0 mg/m^2
Outcomes
Primary Outcome Measures
To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2).
The safety of KW-2478 was determined by reported TEAEs, observed DLTs, changes in PEs, vital sign measurements, ECGs, and laboratory analyses.
The ORR, was defined as the best response over a specified number of cycles (calculated and summarized).
Disease control rate (DCR) was defined as the best response over a specified number of cycles (calculated and summarized). Progression-free survival was defined as the time from the first day of treatment until the date of disease progression or death is first reported (calculated and summarized).
Secondary Outcome Measures
Phase 1: PK Absorption Tmax hr Day 11
Descriptive summary statistics (number, arithmetic mean, standard deviation [SDev], coefficient of variation [CV%]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day.
Phase 1: PK Exposure Cmax ng/mL Day 11
Descriptive summary statistics (number, arithmetic mean, standard deviation [SDev], coefficient of variation [CV%]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day.
Phase 1: PK Exposure AUC0-t hr*ng/mL Day 11
Descriptive summary statistics (number, arithmetic mean, standard deviation [SDev], coefficient of variation [CV%]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day.
Phase 1: PK Elimination t½ hr Day 11
Descriptive summary statistics (number, arithmetic mean, standard deviation [SDev], coefficient of variation [CV%]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day.
Full Information
NCT ID
NCT01063907
First Posted
February 4, 2010
Last Updated
December 1, 2014
Sponsor
Kyowa Hakko Kirin Pharma, Inc.
Collaborators
Kyowa Kirin Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT01063907
Brief Title
A Study of KW-2478 in Combination With Bortezomib in Subjects With Relapsed and/or Refractory Multiple Myeloma
Official Title
An Open Label, Dose Escalation, Multicenter Phase 1/2 Study of KW-2478 in Combination With Bortezomib in Subjects With Relapsed and/or Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
March 2010 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kyowa Hakko Kirin Pharma, Inc.
Collaborators
Kyowa Kirin Co., Ltd.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess the safety and benefits of the investigational study drug, KW-2478, when given with bortezomib (Velcade®), a drug approved for the treatment of Multiple Myeloma (MM).
The primary objectives:
To establish the safety, tolerability, and recommended Phase II dose (RP2D) of KW-2478 in combination with bortezomib (Phase I);
To assess the overall response rate (ORR) when subjects with advanced MM are treated (Phase II).
The secondary objectives:
To characterize the Pharmacokinetic (PK) and Pharmacodynamic (PD) of KW-2478 with bortezomib (Phase I only);
To evaluate for preliminary evidence of efficacy (Phase I);
To determine progression free survival (PFS) and duration of response of KW-2478 with bortezomib (Phase II).
Detailed Description
This is a multicenter, open label, dose escalation, Phase I / II study in subjects with relapsed and/or refractory MM. Up to 24 subjects to be enrolled in the Phase I to determine the RP2D. Up to 77 additional evaluable subjects to be enrolled in Phase II for a maximum up to 101 subjects treated in the study. Study centers in the USA and the UK will participate in Phase I and II. Centers in the Philippines will be participating in Phase II only. The planned enrollment period is 22 months and the planned study duration is 28 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Leukemia, Immunoproliferative Disorder, Neoplasma by Histologic Type, Immune System Diseases, Hematologic Diseases, Blood Protein Disorders, Paraproteinemias, Multiple Myeloma, Hematologic Disorders, Leukemia, Chronic, B-cell, Leukemia, B-cell, Leukemia, Chronic, Neoplasms, Plasma Cell, Monoclonal Gammopathy of unknown significance (MGUS)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
95 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1: Cohort 1
Arm Type
Experimental
Arm Description
Cohort 1: KW 2478 130 mg/m^2 and Bortezomib 1.0 mg/m^2
Arm Title
Phase 1: Cohort 2
Arm Type
Experimental
Arm Description
Cohort 2: KW 2478 130 mg/m^2 and Bortezomib 1.3 mg/m^2
Arm Title
Phase 1: Cohort 3
Arm Type
Experimental
Arm Description
Cohort 3: KW 2478 175 mg/m^2 and Bortezomib 1.0 mg/m^2
Arm Title
Phase 1: Cohort 4
Arm Type
Experimental
Arm Description
Cohort 4: KW 2478 175 mg/m^2 and Bortezomib 1.3 mg/m^2
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
KW 2478 175 mg/m^2 and Bortezomib 1.0 mg/m^2
Intervention Type
Drug
Intervention Name(s)
KW-2478
Other Intervention Name(s)
HSP90 Inhibitor
Intervention Description
Administered Days 1, 4, 8 and 11 of a 21 day cycle
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
Administered on Days 1, 4, 8 and 11 of a 21 day cycle
Primary Outcome Measure Information:
Title
To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2).
Description
The safety of KW-2478 was determined by reported TEAEs, observed DLTs, changes in PEs, vital sign measurements, ECGs, and laboratory analyses.
The ORR, was defined as the best response over a specified number of cycles (calculated and summarized).
Disease control rate (DCR) was defined as the best response over a specified number of cycles (calculated and summarized). Progression-free survival was defined as the time from the first day of treatment until the date of disease progression or death is first reported (calculated and summarized).
Time Frame
21 day cycle, up to 52 weeks
Secondary Outcome Measure Information:
Title
Phase 1: PK Absorption Tmax hr Day 11
Description
Descriptive summary statistics (number, arithmetic mean, standard deviation [SDev], coefficient of variation [CV%]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day.
Time Frame
PK collected Day 11 of 21-day cycle
Title
Phase 1: PK Exposure Cmax ng/mL Day 11
Description
Descriptive summary statistics (number, arithmetic mean, standard deviation [SDev], coefficient of variation [CV%]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day.
Time Frame
PK collected Day 11 of 21-day cycle
Title
Phase 1: PK Exposure AUC0-t hr*ng/mL Day 11
Description
Descriptive summary statistics (number, arithmetic mean, standard deviation [SDev], coefficient of variation [CV%]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day.
Time Frame
PK collected Day 11 of 21-day cycle
Title
Phase 1: PK Elimination t½ hr Day 11
Description
Descriptive summary statistics (number, arithmetic mean, standard deviation [SDev], coefficient of variation [CV%]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day.
Time Frame
PK collected Day 11 of 21-day cycle
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Accepts Healthy Volunteers: No
Inclusion Criteria:
Subjects with a confirmed diagnosis of Multiple Myeloma who have had one and no more than three prior regimens for MM to which they did not respond (failed) or from which they have relapsed.
Signed either an IRB or IEC approved informed consent
ECOG performance status of ≤ 2
Life expectancy of at least 3 months
M protein in either serum or urine, or free light chains if not measurable M protein in serum or urine, and clonal bone marrow plasma cells > 10%, and evidence of end organ damage
Adequate hematologic status, liver and renal function
Subjects of reproductive potential must agree to follow accepted pregnancy prevention methods during the study.
Exclusion Criteria:
No anti-cancer treatment for ≥ 4 weeks and no bortezomib treatment ≥ 60 days prior to receiving study drug
Any other severe, acute or chronic illness
No other prior or concurrent malignancy
No immunosuppressant therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Kurman, MD
Organizational Affiliation
Kyowa Hakko Kirin Pharma, Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Loan Hoang-Sayag, MD
Organizational Affiliation
Quintiles, Inc.
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Noel Pingoy, MD
Organizational Affiliation
Gleneagles CRC
Official's Role
Study Chair
Facility Information:
Facility Name
Arizona Clinical Research Center, Inc. / Arizona Oncology Associates, 1825 N Kolb,
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85715
Country
United States
Facility Name
Pacific Shores Medical Group 1043 Elm Ave, Suite 104
City
Long Beach
State/Province
California
ZIP/Postal Code
90813
Country
United States
Facility Name
UCLA Medical Center Hematology / Oncology Division, 10945 Le Conte Ave #2333,
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-7059
Country
United States
Facility Name
Collaborative Research Group 2320 S Seacrest Blvd, Suite 202
City
Boynton Beach
State/Province
Florida
ZIP/Postal Code
33435
Country
United States
Facility Name
Rush University Medical Center / Division of Hematology/Oncology Research 1725 W Harrison Street, Suite 834
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Cancer Institute of New Jersey 195 Little Albany Street
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903-2681
Country
United States
Facility Name
The Jones Clinic 7710 Wolf River Circle
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
UT MD Anderson Cancer Center, 1515 Holcombe Boulevard,
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Gundersen Clinic Center for Cancer and Blood Disorders, 1900 South Ave, EB2-001,
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
Facility Name
National Kidney and Transplant Institute, Rm 3215 Doctors Clinic, East Avenue
City
Diliman
State/Province
Quezon City
Country
Philippines
Facility Name
Makati Medical Center, New Wing Hall C372, #2 Amorsolo Street, Legaspi Village,
City
Makati City
Country
Philippines
Facility Name
The Medical City, 1609 MATI Building, The Medical City, Ortigas Avenue,
City
Pasig City, Metro Manila
Country
Philippines
Facility Name
Saint Lukes Medical Center, Rm 222 MAB Saint Lukes Medical Center, E. Rodriguez
City
Quezon City
Country
Philippines
Facility Name
Darent Valley Hospital Dept of Haematology, Acorn House, Darenth Wood Road
City
Dartford
State/Province
Kent
ZIP/Postal Code
DA2 8DA
Country
United Kingdom
Facility Name
St Bartholomew's Hospital Haematology Department, 1st Floor, Pathology
City
Dominion House, 59 Bartholomew Close
State/Province
London
ZIP/Postal Code
EC1 7ED
Country
United Kingdom
Facility Name
Christie Hospital - Department Haematology, 550 Wilmslow Road
City
Withington
State/Province
Manchester, Greater Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Hillingdon Hospital Dept of Haematology, Pield Health Road
City
Uxbridge
State/Province
Middlesex
ZIP/Postal Code
UB8 3NN
Country
United Kingdom
Facility Name
Nottingham University Hospitals NHS Trust, Centre for Clinical Haemotology
City
Hucknall Road
State/Province
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Facility Name
Royal Marsden Hospital, Orchard House
City
Downs Road
State/Province
Sutton, Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Facility Name
Royal Bournemouth Hospital, Dept. of Haematolgy, Castle Lane East,
City
Bournemouth
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
Facility Name
Royal Devon & Exeter Hospital Haematology Centre, Barrack Road
City
Exeter
ZIP/Postal Code
EX2 5DW
Country
United Kingdom
Facility Name
Northwick Park Hospital Dept of Haematology, Watford Road
City
Harrow
ZIP/Postal Code
HA1 3UJ
Country
United Kingdom
Facility Name
St James Hospital, St James' Institute of Oncology, Department of Haematology, Level 03, Bexley Wing,
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
UCL Cancer Institute, Paul O'Gorman Building, University College London,72 Huntley Street
City
London
ZIP/Postal Code
WC1E 6DD
Country
United Kingdom
Facility Name
Manchester Royal Infirmary Dept of Haematology, Oxford Road
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
Royal Cornwall Hospital Haematology Clinic
City
Truro
ZIP/Postal Code
TR1 3LS
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study of KW-2478 in Combination With Bortezomib in Subjects With Relapsed and/or Refractory Multiple Myeloma
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