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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation From Family Haploidentical Donors in Patients With Myelodysplastic Syndrome and Acute Leukemia Under Primary Antifungal Prophylaxis With Posaconazole.

Conditions
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Transplant-Related Hematologic Malignancy, Leukemia, Acute, Myelodysplastic Syndromes, Graft Vs Host Disease, Fungal Infection

Intervention / Treatment
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* Drug: Conditioning treatment Thiotepa-Treosulfan-Fludarabine
* Procedure: PBSC graft
* Drug: GvHD prophylaxis
* Drug: Primary antifungal prophylaxis


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm Treatment<br>Conditioning treatment Thiotepa-Treosulfan-Fludarabine; PBSC graft; GvHD prophylaxis; Primary antifungal prophylaxis. | Drug: Conditioning treatment Thiotepa-Treosulfan-Fludarabine<br>* 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.<br>* Other names: TTF;Procedure: PBSC graft<br>* (target 4-8 × 106 CD34+ cells/kg patient body weight)<br>Drug: GvHD prophylaxis<br>* 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.<br>Drug: Primary antifungal prophylaxis<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of antifungal prophylaxis strategy | The rate of proven, probable and possible invasive fungal diseases documented within the first 85 days after transplantation | 85 days after transplantation |