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.

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: AUY922
* Drug: Bortezomib
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Agent AUY922<br> | Drug: AUY922<br> <br> |
| Experimental: AUY922 + Bortezomib<br> | Drug: AUY922<br> <br> Drug: Bortezomib<br> <br> |
| Experimental: AUY922 + Bortezomib + Dexamethasone<br> | Drug: AUY922<br> <br> Drug: Bortezomib<br> <br> Drug: Dexamethasone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safe dose of AUY922 when administered once a week. |  | 54 weeks (Maximum Tolerated Dose (MTD)) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| Efficacy of AUY922 administered once a week alone and in combination |  | at baseline and every 2 cycles (time to document tumor progression) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AUY922, Multiple Myeloma, HSP90 inhibitors, Phase I/II