Multiple MyelomaPhase 1/2NCT01063907
A Study of KW-2478 in Combination With Bortezomib in Subjects With Relapsed and/or Refractory Multiple Myeloma
A Phase 1/2 study testing KW-2478 and Bortezomib in people with Multiple Myeloma, run by Kyowa Kirin Co., Ltd. at 26 sites in 3 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- KW-2478 and Bortezomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 26 sitesin 3 countries
- Study dates
- Mar 2010to Nov 2013
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
26 sites in 3 countries.
26 sites in 3 countries
United Kingdom13 sites
St Bartholomew's Hospital Haematology Department, 1st Floor, Pathology
Barbican, London, EC1 7ED
Royal Bournemouth Hospital, Dept. of Haematolgy, Castle Lane East,
Bournemouth, BH7 7DW
Darent Valley Hospital Dept of Haematology, Acorn House, Darenth Wood Road
Dartford, Kent, DA2 8DA
Royal Devon & Exeter Hospital Haematology Centre, Barrack Road
Exeter, EX2 5DW
Northwick Park Hospital Dept of Haematology, Watford Road
Harrow, HA1 3UJ
St James Hospital, St James' Institute of Oncology, Department of Haematology, Level 03, Bexley Wing,
Leeds, LS9 7TF
UCL Cancer Institute, Paul O'Gorman Building, University College London,72 Huntley Street
London, WC1E 6DD
Manchester Royal Infirmary Dept of Haematology, Oxford Road
Manchester, M13 9WL
Nottingham University Hospitals NHS Trust, Centre for Clinical Haemotology
Nottingham, NG5 1PB
Royal Marsden Hospital, Orchard House
Sutton, Surrey, SM2 5PT
Royal Cornwall Hospital Haematology Clinic
Truro, TR1 3LS
Hillingdon Hospital Dept of Haematology, Pield Health Road
Uxbridge, Middlesex, UB8 3NN
Christie Hospital - Department Haematology, 550 Wilmslow Road
Withington, Manchester, Greater Manchester, M20 4BX
United States9 sites
Collaborative Research Group 2320 S Seacrest Blvd, Suite 202
Boynton Beach, Florida, 33435
Rush University Medical Center / Division of Hematology/Oncology Research 1725 W Harrison Street, Suite 834
Chicago, Illinois, 60612
The Jones Clinic 7710 Wolf River Circle
Germantown, Tennessee, 38138
UT MD Anderson Cancer Center, 1515 Holcombe Boulevard,
Houston, Texas, 77030
Gundersen Clinic Center for Cancer and Blood Disorders, 1900 South Ave, EB2-001,
La Crosse, Wisconsin, 54601
Pacific Shores Medical Group 1043 Elm Ave, Suite 104
Long Beach, California, 90813
UCLA Medical Center Hematology / Oncology Division, 10945 Le Conte Ave #2333,
Los Angeles, California, 90095-7059
Cancer Institute of New Jersey 195 Little Albany Street
New Brunswick, New Jersey, 08903-2681
Arizona Clinical Research Center, Inc. / Arizona Oncology Associates, 1825 N Kolb,
Tucson, Arizona, 85715
Philippines4 sites
National Kidney and Transplant Institute, Rm 3215 Doctors Clinic, East Avenue
Diliman, Quezon City
Makati Medical Center, New Wing Hall C372, #2 Amorsolo Street, Legaspi Village,
Makati City
The Medical City, 1609 MATI Building, The Medical City, Ortigas Avenue,
Pasig, Manila
Saint Lukes Medical Center, Rm 222 MAB Saint Lukes Medical Center, E. Rodriguez
Quezon City
About this study
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
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:
Read more
- 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).
Read the 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
- Being tested
- KW-2478, Bortezomib
- 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)
- Medical subject headings
- Multiple Myeloma, Leukemia, Immunoproliferative Disorders, Immune System Diseases, Hematologic Diseases, Blood Protein Disorders, Paraproteinemias, Leukemia, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KW-2478Drug
Also called HSP90 Inhibitor
Administered Days 1, 4, 8 and 11 of a 21 day cycle
BortezomibDrug
Also called Velcade
Administered on Days 1, 4, 8 and 11 of a 21 day cycle
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Cohort 1 | Experimental | Cohort 1: KW 2478 130 mg/m^2 and Bortezomib 1.0 mg/m^2 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: KW-2478; Drug: Bortezomib |
| Phase 2 | Experimental | KW 2478 175 mg/m^2 and Bortezomib 1.0 mg/m^2 Receives: Drug: KW-2478; Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 21 day cycle, up to 52 weeks
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: PK collected Day 11 of 21-day cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2010 (estimated)
- Study startMar 2010
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Kyowa Kirin Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyowa Kirin Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Kyowa Hakko Kirin Pharma, Inc.
- Responsible party
- Sponsor
- Investigators
- Michael Kurman, MD, Study director, Kyowa Hakko Kirin Pharma, Inc.Loan Hoang-Sayag, MD, Study chair, Quintiles, Inc.Noel Pingoy, MD, Study chair, Gleneagles CRC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01063907
- Sponsor's protocol ID
- 2478-INT-001
- Other IDs
- 2009-016223-56, 2009
- Status last verified
- Apr 2024
- First submitted
- 4 Feb 2010
- Last updated
- 25 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01063907
- Acronym / sponsor ID
- 2478-INT-001
- Conditions
- Multiple Myeloma
- Keywords
- Leukemia, Immunoproliferative Disorder, Neoplasma by Histologic Type, Immune System Diseases, Hematologic Diseases, Blood Protein Disorders, Paraproteinemias, Multiple Myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Kyowa Kirin Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Kyowa Hakko Kirin Pharma, Inc.
- Study start
- Mar 2010
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 5 Feb 2010 (estimated)
- Results
- Posted 5 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Cohort 1 | Experimental | Drug: KW-2478, Drug: BortezomibCohort 1: KW 2478 130 mg/m^2 and Bortezomib 1.0 mg/m^2 |
| Phase 1: Cohort 2 | Experimental | Drug: KW-2478, Drug: BortezomibCohort 2: KW 2478 130 mg/m^2 and Bortezomib 1.3 mg/m^2 |
| Phase 1: Cohort 3 | Experimental | Drug: KW-2478, Drug: BortezomibCohort 3: KW 2478 175 mg/m^2 and Bortezomib 1.0 mg/m^2 |
| Phase 1: Cohort 4 | Experimental | Drug: KW-2478, Drug: BortezomibCohort 4: KW 2478 175 mg/m^2 and Bortezomib 1.3 mg/m^2 |
| Phase 2 | Experimental | Drug: KW-2478, Drug: BortezomibKW 2478 175 mg/m^2 and Bortezomib 1.0 mg/m^2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KW-2478Also: HSP90 InhibitorAdministered Days 1, 4, 8 and 11 of a 21 day cycle | Drug | Phase 1: Cohort 1, Phase 1: Cohort 2, Phase 1: Cohort 3, Phase 1: Cohort 4, Phase 2 |
| BortezomibAlso: VelcadeAdministered on Days 1, 4, 8 and 11 of a 21 day cycle | Drug | Phase 1: Cohort 1, Phase 1: Cohort 2, Phase 1: Cohort 3, Phase 1: Cohort 4, Phase 2 |
Primary outcome
To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2).
Time frame: 21 day cycle, up to 52 weeks
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).
4 secondary outcomes
Phase 1: PK Absorption Tmax hr Day 11
Time frame: PK collected Day 11 of 21-day cycle
Phase 1: PK Exposure Cmax ng/mL Day 11
Time frame: PK collected Day 11 of 21-day cycle
Phase 1: PK Exposure AUC0-t hr*ng/mL Day 11
Time frame: PK collected Day 11 of 21-day cycle
Phase 1: PK Elimination t½ hr Day 11
Time frame: PK collected Day 11 of 21-day cycle
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Kurman, MD study director
Kyowa Hakko Kirin Pharma, Inc.
Loan Hoang-Sayag, MD study chair
Quintiles, Inc.
Noel Pingoy, MD study chair
Gleneagles CRC
26 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing KW-2478 and Bortezomib in people with Multiple Myeloma, run by Kyowa Kirin Co., Ltd. at 26 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United Kingdom, United States, Philippines. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). (time frame: 21 day cycle, up to 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2024.