Graft versus host disease MedDRA version: 18.0 Level: PT Classification code 10053239 Term: Prophylaxis against graft versus host disease System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Trade Name: Rapamune
Product Name: Sirolimus
Product Code: EU/1/01/171/007
Pharmaceutical Form: Coated tablet
INN or Proposed INN: SIROLIMUS
CAS Number: 53123-88-9
Trade Name: Rapamune
Product Name:
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
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 determine which of 2 Graft versus host disease prophylaxis regimens results in a reduction of acute grades II-IV GVHD ;Secondary Objective: 1. Compare non-relapse mortality in the 2 arms. 2. Compare survival and progression-free survival in the 2 arms;Primary end point(s): The goal of the current protocol is to compare in a phase III randomized trial, the effectiveness of 2 GVHD prophylaxis regimens in preventing acute grades II-IV GVHD. Each of the combinations will use CSP every 12 hours through day 96 then tapered off by day 150. Arm 1 (similar to the former unrelated donor nonmyeloablative protocol 1938 Arm 2) will be the “reference arm” in which MMF is given three times a day until day 30 then dropped to twice a day until day 40 with a taper from day 150 through day 180. In Arm 2, sirolimus will be given until day 150 with a taper though day 180. In Arm 2, in addition to CSP and sirolimus, MMF will be given three times a day until day 30, dropped to twice a day and then discontinued on day 40. The current protocol’s primary objective is to reduce the incidence of acute GVHD after unrelated nonmyeloablative HCT. | — |
Countries
Denmark, Germany
Outcome results
None listed