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.

Novartis

Status and phase: Completed; Phase 2; Phase 1

Conditions: Relapsed or Refractory Multiple Myeloma

Treatments: Drug: Bortezomib; Drug: AUY922; Drug: Dexamethasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT00708292

CAUY922A2103

2007-006279-35 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 29 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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29 participants in 3 patient groups

Single Agent AUY922

Experimental group

Treatment:

Drug: AUY922

AUY922 + Bortezomib

Experimental group

Treatment:

Drug: AUY922

Drug: Bortezomib

AUY922 + Bortezomib + Dexamethasone

Experimental group

Treatment:

Drug: AUY922

Drug: Dexamethasone

Drug: Bortezomib