Peripheral Blood Stem Cell Transplantation From Family Haploidentical Donors in Patients With Myelodysplastic Syndrome and Acute Leukemia Under Primary Prophylaxis With Posaconazole

Ciceri Fabio10 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Interventions

Conditioning treatment "Thiotepa-Treosulfan-Fludarabine"DRUG

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.

PBSC graftPROCEDURE

(target 4-8 × 106 CD34+ cells/kg patient body weight)

GvHD prophylaxisDRUG

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.

Primary antifungal prophylaxisDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Graft-versus-host disease-free, relapse-free survival (GRFS)

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

Time frame: 2 years

Secondary Outcomes

Efficacy of antifungal prophylaxis strategy

The rate of proven, probable and possible invasive fungal diseases documented within the first 85 days after transplantation

Time frame: 85 days after transplantation