multiple myeloma MedDRA version: 20.0 Level: LLT Classification code 10028566 Term: Myeloma System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: TEPADINA - 15 MG - POLVERE PER CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO(VETRO) - 10MG/ML 1 FLACONCINO DA 15MG
Product Name: tiotepa
Pharmaceutical Form: Soluti
Sponsors
AZIENDA OSPEDALIERA "BIANCHI-MELACRINO-MORELLI"
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All individuals must meet all of the inclusion criteria in order to be eligible to participate in the study: • Multiple myeloma diagnosis according to IMWG 2014 • Age =18 • Baseline cytogenetics data available • Mobilized stem cells at least 4x106/Kg • At least SD after the first auto-HSCT • Second auto-HSCT if clinical and hematological disease progression, and not earlier than 3 months and not later than 6 months from the first disease progression evidence. • Durie & Salmon stage II-III or I with disease progression. • Karnofsky performance status = 60 • Willing and able to comply with all the protocol requirements. • Adequate hepatic function, with serum (alanine aminotransferase) ALT = 3 times the upper limit of normal and serum direct bilirubin = 2 mg/dL (34 µmol/L) within 14 days prior to randomization • DLCO =40%, TLC =40%, FEV1=40% • Absolute neutrophil count (ANC) = 1.0 × 109/L within 14 days prior to randomization • Platelet count = 50 × 109/L • Creatinine clearance (CrCl) = 30 mL/minute within 7 days prior to randomization, either measured or calculated using a standard formula (eg, Cockcroft and Gault) • Corrected serum calcium = 14 mg/dL (3.5 mmol/L) • LVEF = 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available. • For females of reproductive potential: use of highly effective contraception. Women of child-bearing potential and men must agree to take adequate contraceptive measures in order to avoid any pregnancies of their sexual partners during the course of the study (or for at least 3 months following the last dose of study drug, whichever is longer). Acceptable methods of birth control include oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device IUD) or intrauterine system (IUS), barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/ film/ cream/suppository. Abstinence is only considered an acceptable form of contraception when it is the usual life style of an individual*. • Negative pregnancy test at Screening and at Baseline • Not be breastfeeding • For males of reproductive potential: use of condoms 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 192
Exclusion criteria
Exclusion criteria: An individual who meets any of the following criteria will be excluded from participation in this study: • Diagnosis of smouldering or asymptomatic MM, plasmacell leukemia, solitary plasmocytoma of the bone o extramedullary plasmocytoma. • Diagnosis of non-secretory MM. • Patient not eligible for autologous transplant • Non-adequate organ function (kindneys, liver) • Previous allogeneic transplant • Concomitant enrollment in a clinical study • Concomitant use of a non authorized medication • Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14days prior to randomization • Known human immunodeficiency virus infection (HIV) • Active hepatitis A, B or C infection • Unstable angina or myocardial infarction within 4 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker • DLCO <40%, TLC <40%, FEV1 <40% and/or receiving supplementary continuous oxygen • Non hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas • Significant neuropathy (Grades 3–4, or Grade 2 with pain) within 14 days prior to randomization as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 4.0 (Appendix A) • Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and anti platelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment • Pregnancy or breastfeeding • Unwillingness to use effective contraceptive measures up to 3 months after the end of study drug administration (females and males). • For Women at risk to become pregnant during study participation: positive test for pregnancy (serum) at the time of enrollment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary to evaluate in double transplant program for MM patients if the conditioning regimen based on two alchilant drugs, Melphalan and Thiotepa, can increase the control of the disease in terms of survival free of disease progressioncelltransplantation (auto-HSCT), with two different conditioning regimens in the second auto-HSCT ;Secondary Objective: Secondary -Response rate - PR, VGPR, and CRat day +90 afterthe first ASCT -Response rate - PR, VGPR, and CR at day +90 afterthe second ASCT -duration of response -Event Free Survival rate -Overall Survival -Incidence of TRM -Incidence of hematologic and non-hematologic AEs after ASCT at month +3 after ASCT -Incidence of hematologic and non-hematologic AEs not expected after ASCT at 24 months -Hospitalization;Primary end point(s): PFS at 24 months after the second auto-HSCT ;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary - EFS - OS - TRM - AEs - Hospitalization after ASCT procedure ;Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
Italy
Contacts
Public ContactSegreteria CE
Azienda Ospedaliera "Bianchi-Melacrino-Morelli"
Outcome results
None listed