Myelodysplastic Syndromes (MDS) (20 IPSS LOW+INT-1 and 20 IPSS INT-2+HIGH or proliferating CMML) MedDRA version: 14.1 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Torisel 25 mg/ml concentrate and solvent for the preparation of an infusion solution
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: TEMSIROLIMUS
CAS Number
Sponsors
Dresden Technical University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age greater/equal 18 years at the time of signing the informed consent form; 2. Cytologically or histologically established diagnosis of de novo or therapy-related MDS according to the FAB-classification, either previously treated or untreated, presenting with: Group I (low-risk): Low- or INT-1 risk features according to IPSS and requiring at least 4 units of red blood cells within the last 8 weeks prior to study entry or presenting with neutropenia (=13 Gpt/l) will be included in the high risk arm. 3. Not eligible for an immediate allogeneic HSCT or conventional chemotherapy 4. All previous MDS specific therapies (except supportive approaches like transfusions or antibiotics) must have been discontinued at least 4 weeks prior to study enrollment. 5. ECOG performance status of 25 Gpt/l without transfusion support in patients with LOW- and INT- 1 Risk according to IPSS 7. signed informed consent. 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 40 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. For Patients with LOW- or INT1-Risk according to IPSS: Thrombocytopenia below 25 Gpt/l (INT2- and HIGH-IPSS patients may be included irrespective of platelet count); 2. known hypersensitivity to temsirolimus, sirolimus or any components of the infusion solution (dl-alpha-tocopherol, propylene glycol, anhydrous citric acid, polysorbate 80, polyethylene glycol 400, dehydrated alcohol); 3. known hypersensitivity to macrolid antibiotics (because of structural similarities between this class of antibiotics and study medication); 4. any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study; 5. known positive for HIV or any other uncontrolled infection; 6. presence of any other malignancy being not in complete remission for at least 3 years (previous chemotherapy for other malignancies is not an exclusion criteria); 7. necessity of therapeutic anticoagulation (excluding low dose ASS); 8. participation in an other clinical trial within the last 4 weeks; 9. pregnant or breastfeeding females (lactating females must agree not to breast feed while on study); 10. females of childbearing potential (FCBP) except those fulfilling the following criteria: - post-menopausal (12 months of natural amenorrhea or 6 months of amenorrhea with serum FSH > 40 U/ml); - post-surgery (6 weeks after bilateral ovarectomy with or without hysterectomy); - regular and correct use of contraceptives with a PEARL Index of < 1% (e.g. implants, depot formulations of hormones, oral contraceptives, intra uterine device – IUD); - sexual abstinence; - partner, who had vasectomy (confirmed by two negative analyses of semen); 11. male patients, who do not agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 3 months following discontinuation from the study even if he has undergone a successful vasectomy; 12. patients with a history of chronic drug abuse or another illness which does not allow the patient to assess the nature and/or possible consequences of the study; 13. patients who are not likely to follow the trial protocol (lack of willigness to cooperate).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the response of MDS patients to temsirolimus ;Secondary Objective: - Toxicity as measured by NCI CTCAE v3.0 - Overall survival at 1 year - Progression-free-survival at 1 year - Rate of leukemic progression at 1 year - Overall hematological response rate at 1 year using modified IWG-criteria - Quality of life as measured by EORTC-QLQ30 ;Primary end point(s): Primary endpoint is the overall hematological response rate (combination of CR, PR, marrow-CR and SD with HI) at 4 months using modified IWG-criteria ;Timepoint(s) of evaluation of this end point: 1 . After 4 or 12 months of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints • Toxicity as measured by NCI CTCAE v3.0; • overall survival at 1 year; • progression-free survival at 1 year; • rate of leukemic progression at 1 year; • overall hematological response rate at 1 year using modified IWG-criteria; • quality of life as measured by EORTC-QLQ30. ;Timepoint(s) of evaluation of this end point: every visit | — |
Countries
Germany
Contacts
Public ContactDr. M. Wermke
Universitätsklinikum C. G. Carus an der TU Dresden Medizinische Klinik und Poliklinik I
Outcome results
None listed