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

NCT ID: NCT01063907

Last Updated: 2024-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2013-11-30

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1: Cohort 1

Cohort 1: KW 2478 130 mg/m\^2 and Bortezomib 1.0 mg/m\^2

Group Type: EXPERIMENTAL

KW-2478

Intervention Type: DRUG

Administered Days 1, 4, 8 and 11 of a 21 day cycle

Bortezomib

Intervention Type: DRUG

Administered on Days 1, 4, 8 and 11 of a 21 day cycle

Phase 1: Cohort 2

Cohort 2: KW 2478 130 mg/m\^2 and Bortezomib 1.3 mg/m\^2

Group Type: EXPERIMENTAL

KW-2478

Intervention Type: DRUG

Administered Days 1, 4, 8 and 11 of a 21 day cycle

Bortezomib

Intervention Type: DRUG

Administered on Days 1, 4, 8 and 11 of a 21 day cycle

Phase 1: Cohort 3

Cohort 3: KW 2478 175 mg/m\^2 and Bortezomib 1.0 mg/m\^2

Group Type: EXPERIMENTAL

KW-2478

Intervention Type: DRUG

Administered Days 1, 4, 8 and 11 of a 21 day cycle

Bortezomib

Intervention Type: DRUG

Administered on Days 1, 4, 8 and 11 of a 21 day cycle

Phase 1: Cohort 4

Cohort 4: KW 2478 175 mg/m\^2 and Bortezomib 1.3 mg/m\^2

Group Type: EXPERIMENTAL

KW-2478

Intervention Type: DRUG

Administered Days 1, 4, 8 and 11 of a 21 day cycle

Bortezomib

Intervention Type: DRUG

Administered on Days 1, 4, 8 and 11 of a 21 day cycle

Phase 2

KW 2478 175 mg/m\^2 and Bortezomib 1.0 mg/m\^2

Group Type: EXPERIMENTAL

KW-2478

Intervention Type: DRUG

Administered Days 1, 4, 8 and 11 of a 21 day cycle

Bortezomib

Intervention Type: DRUG

Administered on Days 1, 4, 8 and 11 of a 21 day cycle

Interventions

KW-2478

Administered Days 1, 4, 8 and 11 of a 21 day cycle

Intervention Type: DRUG

Bortezomib

Administered on Days 1, 4, 8 and 11 of a 21 day cycle

Intervention Type: DRUG

Other Intervention Names

HSP90 Inhibitor; Velcade

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyowa Hakko Kirin Pharma, Inc.

INDUSTRY

Sponsor Role: collaborator

Kyowa Kirin Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Kurman, MD

Role: STUDY_DIRECTOR

Kyowa Hakko Kirin Pharma, Inc.

Loan Hoang-Sayag, MD

Role: STUDY_CHAIR

Quintiles, Inc.

Noel Pingoy, MD

Role: STUDY_CHAIR

Gleneagles CRC

Locations

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

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

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

Saint Lukes Medical Center, Rm 222 MAB Saint Lukes Medical Center, E. Rodriguez

Quezon City, , Philippines

Darent Valley Hospital Dept of Haematology, Acorn House, Darenth Wood Road

Dartford, Kent, United Kingdom

St Bartholomew's Hospital Haematology Department, 1st Floor, Pathology

Barbican, London, United Kingdom

Christie Hospital - Department Haematology, 550 Wilmslow Road

Withington, Manchester, Greater Manchester, United Kingdom

Hillingdon Hospital Dept of Haematology, Pield Health Road

Uxbridge, Middlesex, United Kingdom

Royal Marsden Hospital, Orchard House

Sutton, Surrey, United Kingdom

Royal Bournemouth Hospital, Dept. of Haematolgy, Castle Lane East,

Bournemouth, , 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 Cornwall Hospital Haematology Clinic

Truro, , United Kingdom

Countries

United States; Philippines; United Kingdom

Other Identifiers

2009-016223-56

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2478-INT-001

Identifier Type: -

Identifier Source: org_study_id