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.
This study has been completed.
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00708292
First received: June 27, 2008
Last updated: September 25, 2012
Last verified: September 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Relapsed or Refractory Multiple Myeloma |
Drug: AUY922 Drug: Bortezomib Drug: Dexamethasone |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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. |
Resource links provided by NLM:
Drug Information available for:
Dexamethasone
Dexamethasone acetate
Dexamethasone sodium phosphate
Bortezomib
U.S. FDA Resources
Further study details as provided by Novartis:
Primary Outcome Measures:
- The safe dose of AUY922 when administered once a week. [ Time Frame: 54 weeks (Maximum Tolerated Dose (MTD)) ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- 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) ] [ Designated as safety issue: Yes ]
- Efficacy of AUY922 administered once a week alone and in combination [ Time Frame: at baseline and every 2 cycles (time to document tumor progression) ] [ Designated as safety issue: No ]
| Enrollment: | 38 |
| Study Start Date: | July 2008 |
| Study Completion Date: | January 2011 |
| Primary Completion Date: | January 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Single Agent AUY922 | Drug: AUY922 |
| Experimental: AUY922 + Bortezomib | Drug: Bortezomib |
| Experimental: AUY922 + Bortezomib + Dexamethasone | Drug: Dexamethasone |
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00708292
Locations
| United States, Arizona | |
| Mayo Clinic - Arizona Cancer Clinical Research Unit | |
| Scottsdale, Arizona, United States, 85259 | |
| United States, Texas | |
| Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(3) | |
| San Antonio, Texas, United States, 78229 | |
| Australia | |
| Novartis Investigative Site | |
| Melbourne, Australia, 3004 | |
| Germany | |
| Novartis Investigative Site | |
| Frankfurt, Germany, 60590 | |
| Novartis Investigative Site | |
| München, Germany, 81675 | |
| Novartis Investigative Site | |
| Wuerzburg, Germany, 97070 | |
| Singapore | |
| Novartis Investigative Site | |
| Singapore, Singapore, 169608 | |
| Spain | |
| Novartis Investigative Site | |
| Barcelona, Cataluña, Spain, 08036 | |
| Novartis Investigative Site | |
| Madrid, Spain, 28006 | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
No publications provided
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT00708292 History of Changes |
| Other Study ID Numbers: | CAUY922A2103, 2007-006279-35 |
| Study First Received: | June 27, 2008 |
| Last Updated: | September 25, 2012 |
| Health Authority: | United States: Food and Drug Administration Singapore: Health Sciences Authority Spain: Ministry of Health Germany: Federal Institute for Drugs and Medical Devices |
Keywords provided by Novartis:
|
AUY922 Multiple Myeloma HSP90 inhibitors Phase I/II |
Additional relevant MeSH terms:
|
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Dexamethasone acetate |
Dexamethasone Dexamethasone 21-phosphate Bortezomib BB 1101 Anti-Inflammatory Agents Therapeutic Uses Pharmacologic Actions Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Central Nervous System Agents Gastrointestinal Agents Glucocorticoids Hormones |
ClinicalTrials.gov processed this record on June 17, 2013