Transplant-Related Hematologic Malignancy, Leukemia, Acute, Myelodysplastic Syndromes, Graft Vs Host Disease, Fungal Infection
Conditions
Brief summary
SIR-POSA is a phase II trial of peripheral blood stem cell (PBSC) transplantation from a partially compatible family (Haplo) donor in patients with a blood tumor (myelodysplastic syndrome (MDS) and acute leukemia) treated for the prevention of primary fungal infections with posaconazole. The aim is evaluate the composite end-point graft-versus-host disease-free, relapse-free survival (GRFS) in these patients and evaluate the feasibility and efficacy of posaconazole oral tablets as primary antifungal prophylaxis.
Interventions
DRUGConditioning treatment Thiotepa-Treosulfan-Fludarabine
Thiotepa iv 5 mg/kg/bid (total dose TD 10 mg/kg) day -3,-2; Treosulfan iv 14g/mq/day (TD 42 g/mq) as a single daily dose day -6, -5, -4; Fludarabine iv 30 mg/m2 (TD 150 mg/m2) day -6, -5, -4, -3, -2. Thiotepa TD 5 mg/kg and treosulfan TD 36 g/mq dose reduction according to age \> 65 years.
PROCEDUREPBSC graft
(target 4-8 × 106 CD34+ cells/kg patient body weight)
DRUGGvHD prophylaxis
Sirolimus orally, monitored two times a week to maintain a target therapeutic plasma level of 8-15 ng/ml from day +5. Mycophenolate 15 mg/kg bid i.v. or per os day +5 through +28. Cyclophosphamide 50 mg/kg i.v. day +3+4. Mesna: \>80% of the cyclophosphamide dose in 3 divided doses from day +3 daily through day +5.
DRUGPrimary antifungal prophylaxis
Posaconazole delayed-release tablet \[available in 100 mg tablets\]: 300 mg twice daily on the first day followed by a maintenance dose of 300 mg once a day, starting on the day 0 to day 85.
Sponsors
Ciceri Fabio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of myelodysplastic syndromes or acute leukemia * Activation of an alternative donor search by the Italian Bone Marrow Donor Registry (IBMDR) with absence of a 10/10 Human Leukocyte Antigens (HLA) matched unrelated donor * Age \>18 * Unavailability of a HLA-matched related donor (MRD) * Performance status : Eastern Cooperative Oncology Group (ECOG) \<3 * Written and signed informed consent * Life expectancy not severely limited by concomitant illness.
Exclusion criteria
* Women of child-bearing potential who do not agree to abstinence or, if sexually active, do not agree to the use of highly effective method of birth control such as condoms, implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), vasectomised partner on treatment and for at least 6 months thereafter. * Pregnant or nursing (lactating) women. * Known allergies, hypersensitivity, or intolerance to any experimental drugs. * Any active, uncontrolled infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Graft-versus-host disease-free, relapse-free survival (GRFS) | 2 years | GRFS events is defined as the first event among grade III-IV acute Graft vs. Host Disease (GVHD), severe chronic GVHD, relapse and death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of antifungal prophylaxis strategy | 85 days after transplantation | The rate of proven, probable and possible invasive fungal diseases documented within the first 85 days after transplantation |
Countries
Italy
Outcome results
None listed