Graft versus host disease MedDRA version: 18.1 Level: PT Classification code 10053239 Term: Prophylaxis against graft versus host disease System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Pharmaceutical Form:
INN or Proposed INN: Sirolimus
Pharmaceutical Form:
INN or Proposed INN: Mycophenolate mofetil
Pharmaceutical Form:
INN or Proposed INN: Ciclosporine
Sponsors
Fred Hutchinson Cancer Research Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Ages >50 years with hematologic malignancies treatable by unrelated HCT. Ages 40% risk of TRM). Ages =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1) Patients with rapidly progressive intermediate or high grade NHL. 2) Patients with a diagnosis of CMML. 3) Patients with RAEB who have not received myelosuppressive chemotherapy i.e. induction chemotherapy. 4) CNS involvement with disease refractory to intrathecal chemotherapy. 5) Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, MDS, ALL or CML. 6) Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment. 7) Females who are pregnant or breast-feeding. 8) 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. 9) Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month. 10) Organ dysfunction. a. Cardiac ejection fraction 50 years or there is a history of anthracycline exposure or history of cardiac disease. b. Pulmonary: i) DLCO < 40%, TLC <40%, FEV1 <40% and/or receiving supplementary continuous oxygen. ii) The FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules. c. Liver function abnormalities: Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension. 11) Karnofsky scores < 60 or Lansky Score <50 12) Patient has poorly controlled hypertension and on multiple antihypertensives 13) HIV positive patients. 14) Active bacterial or fungal infections unresponsive to medical therapy. 15) All patients receiving antifungal therapy voriconazole, posaconazole, or fluconazole and who are then randomized to ARM2 or ARM 3 must have sirolimus reduced. 16) The addition of cytotoxic agents for “cytoreduction” with the exception of tyrosine kinase inhibitors (such as imatinib), 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 compare the effectiveness of 2GVHD prophylaxis regimens in preventing acute grades II-IV GVHD.;Secondary Objective: 1. Compare non-relapse mortality in the two arms. 2. Compare survival and progression-free survival in the two arms. ;Primary end point(s): The primary endpoint for this trial will be the rate of acute grade II-IV GHVD at day 100 post-transplant, exclusive of GVHD that occurs as a result of alterations to immunosuppressive therapy in response to relapse or progression.;Timepoint(s) of evaluation of this end point: After 150 patients have been randomized and evaluated for 100 days post-transplant, an interim analysis for futility will be conducted. This analysis will estimate the conditional power of the study, given the data available at that time and assuming that going forward the rates of GVHD will differ by 15% between arms, with the rates for each arm centered around the pooled estimate of the rate from the combined arms. The conditional power will be estimated by Monte Carlo simulation. If the estimated conditional power is <33.3% then the trial will be stopped, otherwise the trial will continue to completion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints that will be analyzed include grade III-IV acute GVHD, chronic extensive GVHD, non-relapse mortality, relapse, and overall survival;Timepoint(s) of evaluation of this end point: After 150 patients have been randomized and evaluated for 100 days post-transplant, an interim analysis for futility will be conducted. This analysis will estimate the conditional power of the study, given the data available at that time and assuming that going forward the rates of GVHD will differ by 15% between arms, with the rates for each arm centered around the pooled estimate of the rate from the combined arms. The conditional power will be estimated by Monte Carlo simulation. If the estimated conditional power is <33.3% then the trial will be stopped, otherwise the trial will continue to completion | — |
Countries
Germany, United States
Outcome results
None listed