newly diagnosed multiple myeloma patients MedDRA version: 13.1 Level: HLT Classification code 10028229 Term: Multiple myelomas System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Trade Name: ENDOXAN BAXTER*50CPR RIV 50MG
Pharmaceutical Form: Tablet
INN or Proposed INN: Cyclophosphamide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Tra
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient is of a legally consenting age as defined by local regulations. - Patient is age = 65 year of age or who are ineligible for autologous stem cell transplantation. - Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements. - Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. - Female patient is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. - Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) for the duration of the study. - Patient is a newly diagnosed MM patient. - Patient has measurable disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily, = 0.5 g/dL of M-protein) and, where applicable, urine light-chain excretion of >200 mg/24 hours. For patients with oligo or non-secretory MM, it is required that they have measurable plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of patients admitted to this study will be oligo- or non-secretory MM with free light chains only in order to maximize interpretation of benefit results. - Patient has a Karnofsky performance status =60%. - Patient has a life-expectancy >3 months. - Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1, before study drug administration): - Platelet count =50 x 109/L (=30 x 109 /L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to drug administration). - Absolute neutrophil count (ANC) = 1 x 109/L without the use of growth factors. - Corrected serum calcium =14 mg/dL (3.5 mmol/L) - Alanine transaminase (ALT): = 3 x the ULN. - Total bilirubin: = 2 x the ULN. - Calculated or measured creatinine clearance: = 15 mL/minute 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: - Patients with non-secretory MM, unless serum free light chains are present and the ratio is abnormal. - Pregnant or lactating females - Patient has active infectious hepatitis type B or C or HIV. - Patients with myocardial infarction or unstable angina = 4 months or other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen) - Peripheral neuropathy > CTCAE grade 2 and = grade 2 painful peripheral neuropathy (with the difference being in the exclusion of patients with Grade 2 painful PN). - Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib) - Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preeexisting pulmonary or cardiac impairment. - Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to baseline; - Patient has any other clinically significant illness that would, in the investigator’s opinion, increase the patient’s risk for toxicity. - Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix or breast, or localized prostate cancer of Gleason score <7 with a stable PSA).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine whether the association of Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) as induction treatment is safe and provides benefits in patients with newly diagnosed MM.;Secondary Objective: • Determine the PR and VGPR • Determine the progression free survival (PFS) • Determine the time to progression (TTP) • Determine the duration of response (DOR) • Determine the overall survival (OS) • Time to next therapy (TTNT) • Determine whether responses obtained with CCd treatment are associated with a prolongation of PFS, in comparison with non-responding patients. • Determine whether tumor response and survival might significantly change in particular subgroups of patients defined on prognostic factors (ß2-microglobulin, C-reactive protein (CRP), FISH, gene expression profile). • Determine the rates of peripheral neuropathy • Determine the benefit on PFS and OS of maintenance with intermittent Carfilzomib (once every other weeks).;Primary end point(s): All patients will be included in the Intent-to-Treat (ITT) analysis. Toxicity is defined as the first occurrence of a grade 4 hematologic drug-related toxicity with the exception of anemia (grade 4 neutropenia > 3 days , or grade 4 thrombocytopenia >7 days duration) or a grade = 3 non-haematologic drug-related toxicity. Assessment of adverse events will be performed at the end of third cycle according to the National Cancer Institute Common Terminology Criteria of Adverse Events (CTCAE version 4.0). Efficacy will be assessed by considering partial remissions (PR) following the proposed regimen. Assessment of PR rate will be performed at the end of third cycle according to the criteria of the International Myeloma Working Group. | — |
Countries
Italy
Outcome results
None listed