E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
elderly untreated patients with multiple myeloma. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objective: The primary objectives of this phase I/II study are to identify the most appropriate dose of Carfilzomib in combination with a standard Melphalan Prednisone (MP) treatment regimen (phase I) and to evaluate the efficacy of Carfilzomib plus MP (CMP) in terms of overall response rate [(ORR), consisting of complete response (CR), very good partial response (VGPR), and partial response (PR) (phase II)]. |
|
E.2.2 | Secondary objectives of the trial |
Secondary Objectives: Secondary objectives are to evaluate the safety and tolerability of CMP and to assess efficacy of CMP in terms of clinical benefit response [(CBR = ORR + minimal response (MR)], progression-free survival (PFS), duration of response, and overall survival (OS). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible to enroll in this study. 1. Must understand and voluntarily sign an informed consent form 2. Age > 65 years at the time of signing consent 3. Previously untreated, symptomatic multiple myeloma as defined by the 2 criteria below: • MM diagnostic criteria (all 3 required): o Monoclonal plasma cells in the bone marrow ≥10% and/or presence of a biopsy-proven plasmacytoma o Monoclonal protein present in the serum and/or urine o Myeloma-related organ dysfunction (at least one of the following) [C] Calcium elevation in the blood (serum calcium >10.5 mg/L or upper limit of normal) [R] Renal insufficiency (serum creatinine >2 mg/dL) [A] Anemia (hemoglobin <10 g/dL or 2 g < normal) [B] Lytic bone lesions or osteoporosis AND have measurable disease by protein electrophoresis analyses as defined by the following: • IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level 0.5 g/dL or urine M-protein level 200 mg/24 hours • IgA multiple myeloma: Serum M-protein level 0.5 mg/dL or urine M-protein level 200 mg/24 hours • IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level ≥ 1.0 g/dL or urine M-protein level ≥ 200 mg/24 hours • IgD multiple myeloma: Serum M-protein level 0.05 g/dL or urine M-protein level 200 mg/24 hours • Light chain multiple myeloma: Patients with serum free light chain disease in whom the involved light chain measures ≥ 10 mg/dL 4. ECOG performance status of 0, 1, or 2 5. Able to adhere to the study visit schedule and other protocol requirements 6. Life-expectancy > 3 months 7. Affiliation number to National Health Care System 8. Karnofsky performance status (KPS) of at least 60%
|
|
E.4 | Principal exclusion criteria |
Subjects meeting any of the following exclusion criteria are not eligible to enroll in this study. 1. Previous treatment with antimyeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid [i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 28 days (4 weeks) of consent 2. Any serious medical condition that places the patient at an unacceptable risk if he or she participates in this study. 3. Any of the following laboratory abnormalities • Absolute neutrophil count (ANC) < 1,000 cells/L (1.0 x 109/L) • Platelet count < 50,000 cells/L (50 × 109/L) for patients in whom < 50% of bone marrow nucleated cells are plasma cells; but platelet count < 30,000/L for patients in whom 50% of bone marrow nucleated cells are plasma cells • Serum SGPT/ALT > 3.0× upper limit of normal (ULN); Bilirubin >2× ULN [ALT more specific to liver] • Creatinine clearance ≤ 30 mL/min (Cockcroft-Gault calculation) 4. Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for 3 years. Exceptions include the following: • Basal cell carcinoma of the skin • Squamous cell carcinoma of the skin • Carcinoma in situ of the cervix • Carcinoma in situ of the breast • Incidental histological finding of prostate cancer (TNM stage of T1a or T1b) 5. Peripheral neuropathy of > grade 2 severity. 6. Myocardial infarction within 3 months of enrollment, unstable angina within 2 months or New York Heart Association class III or IV heart failure. 7. Known HIV positivity or active infectious hepatitis, type A, B, or C. 8. Female of childbearing potential 9. Oral or IV fluid hydration contraindicated
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
identify the most appropriate dose of Carfilzomib in combination with a standard Melphalan Prednisone (MP) treatment regimen and to evaluate the efficacy of Carfilzomib plus MP |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
combination of three medicines |
|
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |