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.

Relapsed or Refractory Multiple Myeloma Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00708292
• Other study ID #: CAUY922A2103
• Secondary ID: 2007-006279-35
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 2008
• Est. completion date: January 2011

Study information

• Verified date: June 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed or Refractory Multiple Myeloma

Intervention

Drug:
• AUY922

• Bortezomib

• Dexamethasone

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Melbourne
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Wuerzburg
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
United States	Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(3)	San Antonio	Texas
United States	Mayo Clinic - Arizona Cancer Clinical Research Unit	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Germany,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The safe dose of AUY922 when administered once a week.		54 weeks (Maximum Tolerated Dose (MTD))
Secondary	The safe dose of AUY922 when administered once a week in combination with bortezomib and dexamethasone.		24 weeks (MTD determination of dual and triple combination)
Secondary	Efficacy of AUY922 administered once a week alone and in combination		at baseline and every 2 cycles (time to document tumor progression)

External Links

•   Results for CAUY922A2103 can be found on the Novartis Clinical Trial Results Website