Myelodysplastic Syndrome
Conditions
Keywords
Myelodysplastic Syndromes of all IPSS subgroups
Brief summary
The goal of this Pilot-study is to evaluate the response of unselected MDS patients to temsirolimus a drug approved for the treatment of renal cell cancer. It is planned to give temsirolimus at a weekly dose of 25 mg as intravenous infusion for a maximum duration of 12 months. Regular bone marrow biopsies are planned for controlling MDS response.
Interventions
DRUGTemsirolimus
25 mg/day 1; 8; 15; 22 of each 28-day cycle as intravenous infusion over 30 min
Sponsors
Wyeth is now a wholly owned subsidiary of Pfizer
Technische Universität Dresden
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 years at the time of signing the informed consent form; * Patients able to understand the consequences of participating in this trial and not having any disorders or other circumstances (i.e. being in ward or imprisoned) which keeps them from giving written informed consent; * 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 screening visit or presenting with neutropenia (\<1 Gpt/l neutrophils) or * Group II (high-risk): INT-2 or HIGH-risk IPSS refractory or intolerant to 5-Azacytidine. CMML patients of dysplastic phenotype (WBC \< 13 Gpt/l) may be included in both arms according to IPSS. CMML patients showing proliferative phenotype (WBC \>=13 Gpt/l) will be included in the high risk arm; * not eligible for an immediate allogeneic HSCT or conventional chemotherapy; * all previous MDS specific therapies (except supportive approaches like transfusions or antibiotics) must have been discontinued at least 4 weeks prior to study enrollment; * ECOG performance status of \<= 3 at study entry; * laboratory test results within these ranges: * Serum creatinine \<= 177 µmo/l (\<= 2.0 mg/dL); * total bilirubin \<= 3 x ULN; * AST (SGOT) and ALT (SGPT) \<= 3 x ULN; * total fasting cholesterol \<= 9.1 mmol/l (350 mg/dl); * fasting triglyceride level \<= 4.5 mmol/l (400 mg/dl); * platelets \> 25 Gpt/l without transfusion support in patients with LOW- and INT-1 Risk according to IPSS; * signed informed consent.
Exclusion criteria
* 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); * 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); * known hypersensitivity to macrolid antibiotics (because of structural similarities between this class of antibiotics and study medication); * 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; * known positive for HIV or any other uncontrolled infection; * presence of any other malignancy being not in complete remission for at least 3 years (previous chemotherapy for other malignancies is not an
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall hematological response rate using modified IWG criteria (combination of CR, PR, marrow-CR and SD with HI). | at 4 months |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival | 1 year |
| Progression-free-survival | 1 year |
| Toxicity as measured by NCI CTCAE v3.0 | 4 and 12 months |
| Overall hematological response rate using modified IWG-criteria | 1 year |
| Quality of life as measured by EORTC-QLQ30 | 4 months, 12 months |
| Rate of leukemic progression | 1 year |
Countries
Germany
Outcome results
None listed