Back to resultsA Phase I-Ib/II Study to Determine the Maximum Tolerated Dose (MTD) of AUY922 Alone and in Combination With Bortezomib, With or Without Dexamethasone, in Patients With Relapsed or Refractory Multiple Myeloma.
Primary Purpose
Relapsed or Refractory Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AUY922
Bortezomib
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed or Refractory Multiple Myeloma focused on measuring AUY922, Multiple Myeloma, HSP90 inhibitors, Phase I/II
Eligibility Criteria
Inclusion criteria:
- Patients must have a diagnosis of active multiple myeloma.
- Phase I and Phase II part: Patients must have received at least 2 but not more than 4 prior line of therapy and their disease has progressed during or after last therapy.
- Phase Ib part: Patients must have received no more than 2 prior lines of therapy (excluding dexamethasone as single agent).
- ECOG Performance Status of ≤ 2.
- Patients must have acceptable neutrophil and platelet counts as well as adequate kidney and liver function.
- Patients must have magnesium levels above lower limit of normal or correctable with supplements.
- Patients must be willing and able to undergo bone marrow biopsy/aspirate.
- Able to sign informed consent.
Exclusion criteria:
- Prior treatment with any HSP90 or HDAC inhibitor for the treatment of multiple myeloma.
- Patients with unresolved diarrhea ≥ CTCAE grade 2.
- Patients with acute or chronic liver disease.
- Patients using medications that have a relative risk of prolonging the QT interval.
- Clinically significant cardiac diseases.
- Patients with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome).
- Pregnant or lactating women.
- Fertile women of childbearing potential (WCBP) not using adequate contraception.
- Male patients whose partners are WCBP, not using adequate contraception.
- Patients who unwilling or unable to comply with the protocol.
- Phase Ib part: Peripheral neuropathy ≥ CTCAE grade 1.
- Phase Ib part: Prior treatment with bortezomib.
Other protocol-defined inclusion/exclusion criteria may apply
Sites / Locations
- Mayo Clinic - Arizona Cancer Clinical Research Unit
- Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(3)
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Single Agent AUY922
AUY922 + Bortezomib
AUY922 + Bortezomib + Dexamethasone
Arm Description
Outcomes
Primary Outcome Measures
The safe dose of AUY922 when administered once a week.
Secondary Outcome Measures
The safe dose of AUY922 when administered once a week in combination with bortezomib and dexamethasone.
Efficacy of AUY922 administered once a week alone and in combination
Full Information
NCT ID
NCT00708292
First Posted
June 27, 2008
Last Updated
December 11, 2020
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00708292
Brief Title
A Phase I-Ib/II Study to Determine the Maximum Tolerated Dose (MTD) of AUY922 Alone and in Combination With Bortezomib, With or Without Dexamethasone, in Patients With Relapsed or Refractory Multiple Myeloma.
Official Title
An Open-label, Multi-center, Phase I-Ib/II Study of AUY922 Administered as Single Agent and in Combination With Bortezomib With or Without Dexamethasone in Adult Patients in Relapse or Refractory Multiple Myeloma.
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
January 2011 (Actual)
Study Completion Date
January 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
Brief Summary
This is a Phase I-Ib/II, open-label, multicenter study of AUY922 administered intravenously in patients with multiple myeloma to determine the maximum tolerated dose. The Phase II part will investigate the efficacy of AUY922 in patients with multiple myeloma. Additionally, the study includes a Phase Ib combination part of AUY922 administered in combination with bortezomib, to determine the maximum tolerated dose of the combination drugs in patients with multiple myeloma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed or Refractory Multiple Myeloma
Keywords
AUY922, Multiple Myeloma, HSP90 inhibitors, Phase I/II
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Agent AUY922
Arm Type
Experimental
Arm Title
AUY922 + Bortezomib
Arm Type
Experimental
Arm Title
AUY922 + Bortezomib + Dexamethasone
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AUY922
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Primary Outcome Measure Information:
Title
The safe dose of AUY922 when administered once a week.
Time Frame
54 weeks (Maximum Tolerated Dose (MTD))
Secondary Outcome Measure Information:
Title
The safe dose of AUY922 when administered once a week in combination with bortezomib and dexamethasone.
Time Frame
24 weeks (MTD determination of dual and triple combination)
Title
Efficacy of AUY922 administered once a week alone and in combination
Time Frame
at baseline and every 2 cycles (time to document tumor progression)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Patients must have a diagnosis of active multiple myeloma.
Phase I and Phase II part: Patients must have received at least 2 but not more than 4 prior line of therapy and their disease has progressed during or after last therapy.
Phase Ib part: Patients must have received no more than 2 prior lines of therapy (excluding dexamethasone as single agent).
ECOG Performance Status of ≤ 2.
Patients must have acceptable neutrophil and platelet counts as well as adequate kidney and liver function.
Patients must have magnesium levels above lower limit of normal or correctable with supplements.
Patients must be willing and able to undergo bone marrow biopsy/aspirate.
Able to sign informed consent.
Exclusion criteria:
Prior treatment with any HSP90 or HDAC inhibitor for the treatment of multiple myeloma.
Patients with unresolved diarrhea ≥ CTCAE grade 2.
Patients with acute or chronic liver disease.
Patients using medications that have a relative risk of prolonging the QT interval.
Clinically significant cardiac diseases.
Patients with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome).
Pregnant or lactating women.
Fertile women of childbearing potential (WCBP) not using adequate contraception.
Male patients whose partners are WCBP, not using adequate contraception.
Patients who unwilling or unable to comply with the protocol.
Phase Ib part: Peripheral neuropathy ≥ CTCAE grade 1.
Phase Ib part: Prior treatment with bortezomib.
Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic - Arizona Cancer Clinical Research Unit
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(3)
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Novartis Investigative Site
City
Melbourne
ZIP/Postal Code
3004
Country
Australia
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Novartis Investigative Site
City
München
ZIP/Postal Code
81675
Country
Germany
Facility Name
Novartis Investigative Site
City
Wuerzburg
ZIP/Postal Code
97070
Country
Germany
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28006
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
25809731
Citation
Seggewiss-Bernhardt R, Bargou RC, Goh YT, Stewart AK, Spencer A, Alegre A, Blade J, Ottmann OG, Fernandez-Ibarra C, Lu H, Pain S, Akimov M, Iyer SP. Phase 1/1B trial of the heat shock protein 90 inhibitor NVP-AUY922 as monotherapy or in combination with bortezomib in patients with relapsed or refractory multiple myeloma. Cancer. 2015 Jul 1;121(13):2185-92. doi: 10.1002/cncr.29339. Epub 2015 Mar 24.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=6904
Description
Results for CAUY922A2103 can be found on the Novartis Clinical Trial Results Website
Learn more about this trial
A Phase I-Ib/II Study to Determine the Maximum Tolerated Dose (MTD) of AUY922 Alone and in Combination With Bortezomib, With or Without Dexamethasone, in Patients With Relapsed or Refractory Multiple Myeloma.
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