Hematologic malignancies
Conditions
Interventions
Trade Name: Fludara
Product Name: Fludara
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Fludarabine
CAS Number: 21679-14-1
Other descriptive name: Fludarabine phosphate
Co
Sponsors
Fred Hutchinson Cancer Research Center
Universitätsklinikum Tübingen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ages >50 years with hematologic malignancies treatable by unrelated HCT. 2. Ages 40% risk of TRM). This criterion can include patients with Charleson comorbidity index (CCI) score >139 (see Appendix Q). Transplants should be approved for these inclusion criteria by both the participating institutions’ patient review committees such as the Patient Care Conference (PCC) at the FHCRC and by the principal investigators at the collaborating centers. Patients £ 50 years of age who have received previous high-dose transplantation do not require patient review committee approvals. All children 5% marrow blasts (including those with transformation to AML) must receive cytotoxic chemotherapy and achieve < 5% marrow blasts at time of transplant. Are the trial subjects under 18? no Number of subjects for this
Exclusion criteria
Exclusion criteria: 1. Patients with rapidly progressive intermediate or high grade NHL. 2. CNS involvement with disease refractory to intrathecal chemotherapy. For LP requirement, see Appendix N. 3. Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment. 4. Females who are pregnant. 5. Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years. 6. Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month. 7. Organ dysfunction. a. Cardiac ejection fraction 3 mg/dL, and symptomatic biliary disease. d. Karnofsky scores < 60 (see appendix B). 8. HIV positive patients. 9. Active bacterial or fungal infections unresponsive to medical therapy. 10. All patients receiving voriconazole therapy and who are then randomized to ARM 3 must have voriconazole discontinued (because of the risk of sudden death with concurrent rapamycin therapy) and if indicated, an alternative antifungal therapy should be initiated. 11. The addition of cytotoxic agents for “cytoreduction” with the exception of Gleevec (imatinib mesylate), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or rituxan will not be allowed within three weeks of the initiation of conditioning.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine which of 3 GVHD prophylaxis regimens results in a reduction of acute grades II-IV GVHD to <40%.;Secondary Objective: 1. Reduce the incidence of non-relapse mortality from infections and GVHD before day 200 to < 15%. 2. Reduce the utilization of high-dose corticosteroids compared to protocols 1463, 1641 and 1668. 3. Compare survival and progression-free survival to that achieved under protocols 1463, 1641 and 1668.;Primary end point(s): Fifty patients will be randomized to each arm, with stratification for transplant center (FHCRC vs other), prior courses of chemotherapy (0-2 vs 3+), and age (<55 vs 55+ years). The primary endpoint for this trial will be the rate of acute grade II-IV GHVD. An arm will be declared a ‘success’ if the observed rate of acute grades II-IV GVHD is 40% or less (ie 20 or fewer patients out of 50). Such an outcome would enable one to conclude with at least 90% confidence that the true rate of GVHD was less than 50%. The probability of observing this outcome in an arm is 81%, if the true rate of GVHD for the regimen is 35%. It is hoped that a reduction in the rate of acute GVHD will both translate into reductions in the rate of day 100 non-relapse mortality (currently approximately 15%) and the use of high dose corticosteroids (currently approximately 50%); however, we would not expect to demonstrate statistically significant reductions in these endpoints. | — |
Countries
Germany
Outcome results
None listed