Relapsed or Refractory Multiple Myeloma
Conditions
Keywords
AUY922, Multiple Myeloma, HSP90 inhibitors, Phase I/II
Brief 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.
Interventions
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The safe dose of AUY922 when administered once a week. | 54 weeks (Maximum Tolerated Dose (MTD)) |
Secondary
| Measure | 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) |
Countries
Australia, Germany, Singapore, Spain, United States
Outcome results
None listed