None listed
Conditions
Interventions
The subjects selected for this arm will receive optimal complementary assistance (transfusions according to clinical criteria and antibiotics). In addition to this they will receive Lonafamib (SCH 66336) 200 mg twice a day (BID), orally and continuously. In case of specific toxicities, the dose of the study medication will be reduced to 150 mg BID and finally if necessary to 100 mg BID. This regimen will continue for 12 weeks (3 cycles of 4 weeks each) or until experiencing unacceptable toxicity
The subjects selected for this arm will receive optimal complementary assistance (transfusions according to clinical criteria and antibiotics). In addition to this they will receive Lonafamib Placebo twice a day (BID), orally and continuously. In case of specific toxicities, the dose can be reduced. This regimen will continue for 12 weeks (3 cycles of 4 weeks each) or until experiencing unacceptable toxicity or transformation into AML.
Sponsors
SCHERING PLOUGH RESEARCH INSTITUTE,
Eligibility
Inclusion criteria
Inclusion criteria: 1. Pathologically documented MDS, confirmed by bone marrow aspirate (BMA) performed before randomization. 2. To meet eligibility conditions in the selection: Subjects must have data on platelet transfusions and RBC, and hemoglobin and platelet values ​​available for a period of 8 weeks prior to the first day of selection. 3. To meet the eligibility conditions for randomization: Platelet transfusion and RBC data, and hemoglobin and platelet values ​​obtained during the 4-week prospective selection should confirm the results of the retrospective selection phase. 4. Age> or equal to 18 years. 5. More than 12 weeks elapsed (before Day -1) from the use of any drug in the research phase. 6. ECOG performance status from 0 to 2. 7. Laboratory parameters: serum creatinine <1.5 times the upper limit of normal. Total bilirubin <2 mg / dl, SGOT or SGPT <2.5 x the upper limit of normal, or alkaline phosphatase <4 x the upper limit of normal. 8. More than 12 weeks elapsed (before Day -1) from the administration of any chemotherapy, radiotherapy or immunotherapy. 9. More than 12 weeks elapsed (before Day -1) from the administration of any treatment for MDS / CMM. 10. More than 24 weeks elapsed (before Day ~ 1) after bone marrow or peripheral blood stem cell transplantation or treatment with donor lymphocyte infusion. 11. More than 12 weeks elapsed (before Day -1) from the administration of any treatment with Oprelvekin (Neumega) and treatment with erythropoietin / darbopoietin unless it is administered in stable doses. 12 Men and women who can procreate will have to be using an effective method of contraception. 13 The informed consent of the subject for the treatment and follow-up will be obtained and documented
Exclusion criteria
Exclusion criteria: 1. Subjects with MDS associated with chemotherapy / radiotherapy do not meet eligibility conditions. 2. Subjects in serious medical risk due to systematic non-malignant disease or with controlled active infection. 3. Subjects with nausea> grade 2 or vomiting> grade 1 or with any condition that might interfere with oral medication intake. 4. Subjects with known HIV positivity or AIDS-related disease. 5. Subjects with active mental or psychiatric illness that make the understanding of informed consent and careful clinical follow-up unlikely. 6. Pregnant or lactating women. 7. Subjects with current or previous exposure to famesyl transferase inhibitors. 8. Subjects with current treatment for MDS / CMML with the exception of optimal complementary assistance. 9. Subjects with evidence of another malignancy within 5 years.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Complete haematological panel: White cells, neutrophils, bands, monocytes, hemoglobin, hematocrit, platelets, peripheral blood blasts Measure:Efficacy of treatment: Independence of platelet transfusion during any period of 8 consecutive weeks, without worsening the requirements for RBC transfusions or hemoglobin during the same period of 8 consecutive weeks. Timepoints:Days 1, 8, 15 and 22 of each cycle | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:1) Haematological response rate: Complete haematological panel (white cells, neutrophils, bands, monocytes, hemoglobin, hematocrit, platelets, blasts in peripheral blood) and bone marrow aspirate 2) Average transfusion requirement: Complete haematological panel (White cells, neutrophils, bands, monocytes, hemoglobin, hematocrit, platelets, peripheral blood blasts) 3) Active bleeding: Clinical evaluation 4) Infections grade 3 or 4: Clinical evaluation Measure:1) Hematological response rate: Complete remission, partial remission and haematological improvement. 2) Average transfusion requirement 3) Active bleeding 4) Infections grade 3 or 4 Timepoints:Complete hematological panel: Days 1, 8, 15 and 22 of each cycle. Bone marrow aspiration: Day 1 of the first cycle and last day of the fourth cycle Clinical evaluation: Day 1 of each cycle and day 29 of the fourth cycle (end of cycle). ; Outcome name:Chemical panel: Na, K, total bilirubin, SGOT, SGPT, LDH, alkaline phosphatase, creatinine. Review of adverse effects. Measure:Treatment safety Timepoints:Chemical panel: Days 1 of each cycle and last day of the fourth cycle. Review of adverse effects: Days 1 of each cycle and last day of the fourth cycle. ; Outcome name:Pharmacokinetics: Peripheral blood samples Pharmacodynamics: Peripheral blood samples. Pharmacogenomics: Peripheral blood and bone marrow samples Measure:Pharmacokinetics, pharmacodynamics and pharmacogenomics of the study drug Timepoints:Peripheral blood samples: Day 1 of cycles 1 to 3 Bone marrow sample: Day 1 of cycles 1 to 3 | — |
Countries
Austria, Canada, China, Colombia, Czech Republic, Ecuador, El Salvador, Germany, Greece, Italy, Peru, Singapore, Spain, United States
Contacts
Public ContactJorge Timoteo
SCHERING PLOUGH DEL PERU S.A.
Outcome results
None listed