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

NCT01063907 | Completed Phase 1 Results

• 2 other identifiers: 2478-INT-0012009-016223-56
• Study Type: interventional
• Target: 95
• Locations: 3 countries
• Sites: 26

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).

Conditions

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)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Phase 1: PK Absorption Tmax hr Day 11

  PK collected Day 11 of 21-day cycle

• Phase 1: PK Exposure Cmax ng/mL Day 11

  PK collected Day 11 of 21-day cycle

• Phase 1: PK Exposure AUC0-t hr*ng/mL Day 11

  PK collected Day 11 of 21-day cycle

• Phase 1: PK Elimination t½ hr Day 11

  PK collected Day 11 of 21-day cycle

Study Arms (5)

Phase 1: Cohort 1

EXPERIMENTAL

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

Drug: KW-2478; Drug: Bortezomib

Phase 1: Cohort 2

EXPERIMENTAL

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

Drug: KW-2478; Drug: Bortezomib

Phase 1: Cohort 3

EXPERIMENTAL

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

Drug: KW-2478; Drug: Bortezomib

Phase 1: Cohort 4

EXPERIMENTAL

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

Drug: KW-2478; Drug: Bortezomib

Phase 2

EXPERIMENTAL

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

Drug: KW-2478; Drug: Bortezomib

Interventions

KW-2478 DRUG

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

Also known as: HSP90 Inhibitor

Phase 1: Cohort 1; Phase 1: Cohort 2; Phase 1: Cohort 3; Phase 1: Cohort 4; Phase 2

Bortezomib DRUG

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

Also known as: Velcade

Phase 1: Cohort 1; Phase 1: Cohort 2; Phase 1: Cohort 3; Phase 1: Cohort 4; Phase 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead
• Kyowa Hakko Kirin Pharma, Inc.: collaborator

Study Sites (26)

Arizona Clinical Research Center, Inc. / Arizona Oncology Associates, 1825 N Kolb,

Tucson, Arizona, 85715, United States

Location

Pacific Shores Medical Group 1043 Elm Ave, Suite 104

Long Beach, California, 90813, United States

Location

UCLA Medical Center Hematology / Oncology Division, 10945 Le Conte Ave #2333,

Los Angeles, California, 90095-7059, United States

Location

Collaborative Research Group 2320 S Seacrest Blvd, Suite 202

Boynton Beach, Florida, 33435, United States

Location

Rush University Medical Center / Division of Hematology/Oncology Research 1725 W Harrison Street, Suite 834

Chicago, Illinois, 60612, United States

Location

Cancer Institute of New Jersey 195 Little Albany Street

New Brunswick, New Jersey, 08903-2681, United States

Location

The Jones Clinic 7710 Wolf River Circle

Germantown, Tennessee, 38138, United States

Location

UT MD Anderson Cancer Center, 1515 Holcombe Boulevard,

Houston, Texas, 77030, United States

Location

Gundersen Clinic Center for Cancer and Blood Disorders, 1900 South Ave, EB2-001,

La Crosse, Wisconsin, 54601, United States

Location

The Medical City, 1609 MATI Building, The Medical City, Ortigas Avenue,

Pasig, Manila, Philippines

Location

National Kidney and Transplant Institute, Rm 3215 Doctors Clinic, East Avenue

Diliman, Quezon City, Philippines

Location

Makati Medical Center, New Wing Hall C372, #2 Amorsolo Street, Legaspi Village,

Makati City, Philippines

Location

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

Quezon City, Philippines

Location

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

Dartford, Kent, DA2 8DA, United Kingdom

Location

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

Barbican, London, EC1 7ED, United Kingdom

Location

Christie Hospital - Department Haematology, 550 Wilmslow Road

Withington, Manchester, Greater Manchester, M20 4BX, United Kingdom

Location

Hillingdon Hospital Dept of Haematology, Pield Health Road

Uxbridge, Middlesex, UB8 3NN, United Kingdom

Location

Royal Marsden Hospital, Orchard House

Sutton, Surrey, SM2 5PT, United Kingdom

Location

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

Bournemouth, BH7 7DW, United Kingdom

Location

Royal Devon & Exeter Hospital Haematology Centre, Barrack Road

Exeter, EX2 5DW, United Kingdom

Location

Northwick Park Hospital Dept of Haematology, Watford Road

Harrow, HA1 3UJ, United Kingdom

Location

St James Hospital, St James' Institute of Oncology, Department of Haematology, Level 03, Bexley Wing,

Leeds, LS9 7TF, United Kingdom

Location

UCL Cancer Institute, Paul O'Gorman Building, University College London,72 Huntley Street

London, WC1E 6DD, United Kingdom

Location

Manchester Royal Infirmary Dept of Haematology, Oxford Road

Manchester, M13 9WL, United Kingdom

Location

Nottingham University Hospitals NHS Trust, Centre for Clinical Haemotology

Nottingham, NG5 1PB, United Kingdom

Location

Royal Cornwall Hospital Haematology Clinic

Truro, TR1 3LS, United Kingdom

Location

MeSH Terms

Conditions

Multiple Myeloma; Leukemia; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases; Blood Protein Disorders; Paraproteinemias; Leukemia, B-Cell; Bronchiolitis Obliterans Syndrome; Neoplasms, Plasma Cell; Monoclonal Gammopathy of Undetermined Significance

Interventions

KW-2478; Hsp90 inhibitor KU757; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Leukemia, Lymphoid; Lymphatic Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Hypergammaglobulinemia

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior VP Drug Development
• Organization: Kyowa Hakko Kirin Pharma, Inc.

clinical.info@kyowa-kirin-pharma.com

609-919-1100

Study Officials

• Michael Kurman, MD

  Kyowa Hakko Kirin Pharma, Inc.

  STUDY DIRECTOR

• Loan Hoang-Sayag, MD

  Quintiles, Inc.

  STUDY CHAIR

• Noel Pingoy, MD

  Gleneagles CRC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2010
• First Posted: February 5, 2010
• Study Start: March 1, 2010
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: April 25, 2024
• Results First Posted: November 5, 2014

Record last verified: 2024-04

Locations

US (9); PH (4); GB (13)