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.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
First received: June 27, 2008
Last updated: June 30, 2015
Last verified: June 2015
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: Parallel 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:

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: 29
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: AUY922 Drug: Bortezomib
Experimental: AUY922 + Bortezomib + Dexamethasone Drug: AUY922 Drug: Bortezomib Drug: Dexamethasone


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00708292

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
Novartis Investigative Site
Melbourne, Australia, 3004
Novartis Investigative Site
Frankfurt, Germany, 60590
Novartis Investigative Site
München, Germany, 81675
Novartis Investigative Site
Wuerzburg, Germany, 97070
Novartis Investigative Site
Singapore, Singapore, 169608
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site
Madrid, Spain, 28006
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

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: June 30, 2015
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:
Multiple Myeloma
HSP90 inhibitors
Phase I/II

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Vascular Diseases
BB 1101
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Enzyme Inhibitors
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 25, 2016