A Study of KW-2478 in Combination With Bortezomib in Subjects With Relapsed and/or Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01063907
• Other study ID #: 2478-INT-001
• Secondary ID: 2009-016223-56
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2010
• Est. completion date: November 2013

Study information

• Verified date: April 2024
• Source: Kyowa Kirin Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 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.

2. Signed either an IRB or IEC approved informed consent

3. ECOG performance status of = 2

4. Life expectancy of at least 3 months

5. 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

6. Adequate hematologic status, liver and renal function

7. Subjects of reproductive potential must agree to follow accepted pregnancy prevention methods during the study.

Exclusion Criteria:

1. No anti-cancer treatment for = 4 weeks and no bortezomib treatment = 60 days prior to receiving study drug

2. Any other severe, acute or chronic illness

3. No other prior or concurrent malignancy

4. No immunosuppressant therapy

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• KW-2478
Administered Days 1, 4, 8 and 11 of a 21 day cycle
• Bortezomib
Administered on Days 1, 4, 8 and 11 of a 21 day cycle

Locations

Country	Name	City	State
Philippines	National Kidney and Transplant Institute, Rm 3215 Doctors Clinic, East Avenue	Diliman	Quezon City
Philippines	Makati Medical Center, New Wing Hall C372, #2 Amorsolo Street, Legaspi Village,	Makati City
Philippines	The Medical City, 1609 MATI Building, The Medical City, Ortigas Avenue,	Pasig City	Manila
Philippines	Saint Lukes Medical Center, Rm 222 MAB Saint Lukes Medical Center, E. Rodriguez	Quezon City
United Kingdom	St Bartholomew's Hospital Haematology Department, 1st Floor, Pathology	Barbican	London
United Kingdom	Royal Bournemouth Hospital, Dept. of Haematolgy, Castle Lane East,	Bournemouth
United Kingdom	Darent Valley Hospital Dept of Haematology, Acorn House, Darenth Wood Road	Dartford	Kent
United Kingdom	Royal Devon & Exeter Hospital Haematology Centre, Barrack Road	Exeter
United Kingdom	Northwick Park Hospital Dept of Haematology, Watford Road	Harrow
United Kingdom	St James Hospital, St James' Institute of Oncology, Department of Haematology, Level 03, Bexley Wing,	Leeds
United Kingdom	UCL Cancer Institute, Paul O'Gorman Building, University College London,72 Huntley Street	London
United Kingdom	Manchester Royal Infirmary Dept of Haematology, Oxford Road	Manchester
United Kingdom	Nottingham University Hospitals NHS Trust, Centre for Clinical Haemotology	Nottingham
United Kingdom	Royal Marsden Hospital, Orchard House	Sutton	Surrey
United Kingdom	Royal Cornwall Hospital Haematology Clinic	Truro
United Kingdom	Hillingdon Hospital Dept of Haematology, Pield Health Road	Uxbridge	Middlesex
United Kingdom	Christie Hospital - Department Haematology, 550 Wilmslow Road	Withington	Manchester, Greater Manchester
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	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	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	Cancer Institute of New Jersey 195 Little Albany Street	New Brunswick	New Jersey
United States	Arizona Clinical Research Center, Inc. / Arizona Oncology Associates, 1825 N Kolb,	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Kyowa Kirin Co., Ltd.	Kyowa Hakko Kirin Pharma, Inc.

Countries where clinical trial is conducted

United States,  Philippines,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	21 day cycle, up to 52 weeks
Secondary	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.	PK collected Day 11 of 21-day cycle
Secondary	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.	PK collected Day 11 of 21-day cycle
Secondary	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.	PK collected Day 11 of 21-day cycle
Secondary	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.	PK collected Day 11 of 21-day cycle