adult patients with relapsed or refractory multiple myeloma MedDRA version: 12.0 Level: LLT Classification code 10028228 Term: Multiple myeloma
Conditions
Interventions
Product Code: AUY922
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 747412-49-3
Current Sponsor code: AUY922
Concentration unit: mg/ml milligram(s)/millilitre
Concentration typ
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria 1. Patients must have a diagnosis of active MM according to the International Myeloma Working Group criteria (Durie et al. 2006): • • Presence of an M-component in serum or urine (in patients with no detectable M-component, an abnormal FLC ratio on the serum FLC assay can substitute this criteria), • Clonal Plasma cells in the bone marrow (= 10% of clonal plasma cells) and/or documented clonal plasmacytoma, PLUS one or more of the following attributable to plasma cell disorder at the time of diagnosis: • Calcium elevation (?11.5 mg/dl), • Renal insufficiency (Creatinine ? 2 mg/dl), • Anemia (Hemoglobin ? 10g/dl or 2g/dl ? normal), • Bone disease (lytic lesions or osteopenia). 2. AUY922 single agent (Phase I dose escalation & Phase II dose expansion parts) • Patients with relapsed-refractory MM (please refer to Post-text supplement 2) who received at least two but no more than three prior anti-myeloma regimens had progressed during or after the last therapy. • Prior therapy must include at least one of the following: bortezomib or lenalidomide or thalidomide. • Induction therapy followed by any kind of stem cell transplantation and/or maintenance therapy is considered as 1 regimen. • AUY922 in combination (Phase Ib dose escalation part) • Patients with relapsed-refractory MM (please refer to Post-text supplement 2) who received no more than two prior anti-myeloma regimens (excluding dexamethasone as single agent). • Patients must be suitable (according to their local product information) for treatment with bortezomib. Note: patients previously treated with lenalidomide or thalidomide are eligible to participate in the trial. • Induction therapy followed by any kind of stem cell transplantation and/or maintenance therapy is considered as 1 regimen. 5. Age = 18 years. 6. ECOG Performance Status of = 2. 7. Life expectancy of = 12 weeks. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with non-secretory MM. 2. Patients who have received allogenic stem cell transplantation ? 12 months prior to enter in the study. 3. Patients who have received allogenic stem cell transplantation and show evidence of active graft-versus-host disease that requires immunosuppressive therapy. 4. Patients with unresolved diarrhea = CTCAE grade 2. 5. Patients with acute or chronic liver disease. 6. Peripheral neuropathy = CTCAE grade 1 (only for patients in the combination part of the study). 7. Other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol. 8. Pregnant or lactating women. 9. Fertile women of childbearing potential (WCBP) not using adequate contraception (abstinence, oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile). Male patients whose partners are WCBP, not using adequate contraception. 10. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective dose escalation parts • To determine the MTD of AUY922 as a single agent and in combination with bortezomib administered with or without dexamethasone, when administered in adult patients with MM. Primary objective dose expansion part • At the MTD level, to assess the preliminary efficacy in patients with MM treated with AUY922 as a single agent. ;Secondary Objective: Secondary objectives • To assess the preliminary efficacy in patients with MM treated with AUY922 as a single agent and in combination with bortezomib administered with or without dexamethasone (dose escalation parts). • To assess the safety and tolerability of AUY922 as a single agent and in combination with bortezomib administered with or without dexamethasone. • To assess the PK profile of AUY922 as a single agent, and of AUY922 as well as bortezomib in the combination treatment with or without dexamethasone, including the parent drugs and any potential metabolite/s when feasible and explore potential PK and PD relationships. • To assess evidence of activity of AUY922 treatment, soluble free light chains will be measured using the FreeLiteTM assay. • To assess changes in PD markers of target modulation as a measure of HSP90 inhibition, pre- and post-AUY922 dosing bone marrow aspirate samples will be compared for their levels of such markers as IL6R, IGFR1, AKT and HSP70. ;Primary end point(s): Primary endpoint dose escalation parts • Incidence rate of Dose Limiting Toxicities (DLT). Primary endpoint dose expansion part • Efficacy: Response based on the modified EBMT/IMWG response criteria (Anderson et al. 2007). | — |
Countries
Germany
Outcome results
None listed