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:
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
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 September 18, 2014