Clinical trial NCT01063907: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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)
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Kyowa Hakko Kirin Pharma, Inc.
First posted: 2010-02-05
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2).
timeFrame: 21 day cycle, up to 52 weeks
Secondary outcomes:
measure: Phase 1: PK Absorption Tmax hr Day 11
timeFrame: PK collected Day 11 of 21-day cycle
measure: Phase 1: PK Exposure Cmax ng/mL Day 11
timeFrame: PK collected Day 11 of 21-day cycle
measure: Phase 1: PK Exposure AUC0-t hr*ng/mL Day 11
timeFrame: PK collected Day 11 of 21-day cycle
measure: Phase 1: PK Elimination t½ hr Day 11
timeFrame: PK collected Day 11 of 21-day cycle
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center, Inc. / Arizona Oncology Associates, 1825 N Kolb,
state: Arizona
city: Long Beach
country: United States
facility: Pacific Shores Medical Group 1043 Elm Ave, Suite 104
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center Hematology / Oncology Division, 10945 Le Conte Ave #2333,
state: California
city: Boynton Beach
country: United States
facility: Collaborative Research Group 2320 S Seacrest Blvd, Suite 202
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center / Division of Hematology/Oncology Research 1725 W Harrison Street, Suite 834
state: Illinois
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey 195 Little Albany Street
state: New Jersey
city: Germantown
country: United States
facility: The Jones Clinic 7710 Wolf River Circle
state: Tennessee
city: Houston
country: United States
facility: UT MD Anderson Cancer Center, 1515 Holcombe Boulevard,
state: Texas
city: La Crosse
country: United States
facility: Gundersen Clinic Center for Cancer and Blood Disorders, 1900 South Ave, EB2-001,
state: Wisconsin
city: Pasig City
country: Philippines
facility: The Medical City, 1609 MATI Building, The Medical City, Ortigas Avenue,
state: Manila
city: Diliman
country: Philippines
facility: National Kidney and Transplant Institute, Rm 3215 Doctors Clinic, East Avenue
state: Quezon City
city: Makati City
country: Philippines
facility: Makati Medical Center, New Wing Hall C372, #2 Amorsolo Street, Legaspi Village,
city: Quezon City
country: Philippines
facility: Saint Lukes Medical Center, Rm 222 MAB Saint Lukes Medical Center, E. Rodriguez
city: Dartford
country: United Kingdom
facility: Darent Valley Hospital Dept of Haematology, Acorn House, Darenth Wood Road
state: Kent
city: Barbican
country: United Kingdom
facility: St Bartholomew's Hospital Haematology Department, 1st Floor, Pathology
state: London
city: Withington
country: United Kingdom
facility: Christie Hospital - Department Haematology, 550 Wilmslow Road
state: Manchester, Greater Manchester
city: Uxbridge
country: United Kingdom
facility: Hillingdon Hospital Dept of Haematology, Pield Health Road
state: Middlesex
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital, Orchard House
state: Surrey
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital, Dept. of Haematolgy, Castle Lane East,
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter Hospital Haematology Centre, Barrack Road
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital Dept of Haematology, Watford Road
city: Leeds
country: United Kingdom
facility: St James Hospital, St James' Institute of Oncology, Department of Haematology, Level 03, Bexley Wing,
city: London
country: United Kingdom
facility: UCL Cancer Institute, Paul O'Gorman Building, University College London,72 Huntley Street
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary Dept of Haematology, Oxford Road
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust, Centre for Clinical Haemotology
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital Haematology Clinic
Study officials:
affiliation: Kyowa Hakko Kirin Pharma, Inc.
name: Michael Kurman, MD
role: STUDY_DIRECTOR
affiliation: Quintiles, Inc.
name: Loan Hoang-Sayag, MD
role: STUDY_CHAIR
affiliation: Gleneagles CRC
name: Noel Pingoy, MD
role: STUDY_CHAIR
References: