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).
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
95
Administered Days 1, 4, 8 and 11 of a 21 day cycle
Administered on Days 1, 4, 8 and 11 of a 21 day cycle
Arizona Clinical Research Center, Inc. / Arizona Oncology Associates, 1825 N Kolb,
Tucson, Arizona, United States
Pacific Shores Medical Group 1043 Elm Ave, Suite 104
Long Beach, California, United States
UCLA Medical Center Hematology / Oncology Division, 10945 Le Conte Ave #2333,
Los Angeles, California, United States
Collaborative Research Group 2320 S Seacrest Blvd, Suite 202
Boynton Beach, Florida, United States
Rush University Medical Center / Division of Hematology/Oncology Research 1725 W Harrison Street, Suite 834
Chicago, Illinois, United States
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).
Time frame: 21 day cycle, up to 52 weeks
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.
Time frame: PK collected Day 11 of 21-day cycle
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.
Time frame: PK collected Day 11 of 21-day cycle
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.
Time frame: PK collected Day 11 of 21-day cycle
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.
Time frame: PK collected Day 11 of 21-day cycle
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Cancer Institute of New Jersey 195 Little Albany Street
New Brunswick, New Jersey, United States
The Jones Clinic 7710 Wolf River Circle
Germantown, Tennessee, United States
UT MD Anderson Cancer Center, 1515 Holcombe Boulevard,
Houston, Texas, United States
Gundersen Clinic Center for Cancer and Blood Disorders, 1900 South Ave, EB2-001,
La Crosse, Wisconsin, United States
The Medical City, 1609 MATI Building, The Medical City, Ortigas Avenue,
Pasig, Manila, Philippines
...and 16 more locations