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

Myelodysplastic Syndromes Clinical Trial

— SIR-POSA  

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03434704
• Other study ID #: 2017-004423-78
• Status: Completed
• Phase: Phase 2
• Start date: June 18, 2018
• Est. completion date: October 13, 2019

Study information

• Verified date: July 2022
• Source: IRCCS San Raffaele
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 13, 2019
• Est. primary completion date: October 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fungal Infection
• Graft Vs Host Disease
• Hematologic Neoplasms
• Leukemia
• Leukemia, Acute
• Mycoses
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome
• Transplant-Related Hematologic Malignancy

Intervention

Drug:
• Conditioning 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.

Procedure:
• PBSC graft
(target 4-8 × 106 CD34+ cells/kg patient body weight)

Drug:
• GvHD 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.
• Primary 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.

Locations

Country	Name	City	State
Italy	Ospedale San Raffaele	Milano	Lombardia

Sponsors (1)

Lead Sponsor	Collaborator
Ciceri Fabio

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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