Back to resultsPeripheral Blood Stem Cell Transplantation From Family Haploidentical Donors in Patients With Myelodysplastic Syndrome and Acute Leukemia Under Primary Prophylaxis With Posaconazole (SIR-POSA)
Primary Purpose
Transplant-Related Hematologic Malignancy, Leukemia, Acute, Myelodysplastic Syndromes
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Conditioning treatment "Thiotepa-Treosulfan-Fludarabine"
PBSC graft
GvHD prophylaxis
Primary antifungal prophylaxis
Sponsored by
About this trial
This is an interventional treatment trial for Transplant-Related Hematologic Malignancy
Eligibility Criteria
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.
Sites / Locations
- Ospedale San Raffaele
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single Arm Treatment
Arm Description
Conditioning treatment "Thiotepa-Treosulfan-Fludarabine"; PBSC graft; GvHD prophylaxis; Primary antifungal prophylaxis.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Efficacy of antifungal prophylaxis strategy
The rate of proven, probable and possible invasive fungal diseases documented within the first 85 days after transplantation
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03434704
Brief Title
Peripheral Blood Stem Cell Transplantation From Family Haploidentical Donors in Patients With Myelodysplastic Syndrome and Acute Leukemia Under Primary Prophylaxis With Posaconazole
Acronym
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.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
June 18, 2018 (Actual)
Primary Completion Date
October 13, 2019 (Actual)
Study Completion Date
October 13, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ciceri Fabio
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transplant-Related Hematologic Malignancy, Leukemia, Acute, Myelodysplastic Syndromes, Graft Vs Host Disease, Fungal Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Arm Treatment
Arm Type
Experimental
Arm Description
Conditioning treatment "Thiotepa-Treosulfan-Fludarabine"; PBSC graft; GvHD prophylaxis; Primary antifungal prophylaxis.
Intervention Type
Drug
Intervention Name(s)
Conditioning treatment "Thiotepa-Treosulfan-Fludarabine"
Other Intervention Name(s)
TTF
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
PBSC graft
Intervention Description
(target 4-8 × 106 CD34+ cells/kg patient body weight)
Intervention Type
Drug
Intervention Name(s)
GvHD prophylaxis
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Primary antifungal prophylaxis
Intervention Description
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.
Primary Outcome Measure Information:
Title
Graft-versus-host disease-free, relapse-free survival (GRFS)
Description
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 Outcome Measure Information:
Title
Efficacy of antifungal prophylaxis strategy
Description
The rate of proven, probable and possible invasive fungal diseases documented within the first 85 days after transplantation
Time Frame
85 days after transplantation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Ospedale San Raffaele
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
12. IPD Sharing Statement
Learn more about this trial
Peripheral Blood Stem Cell Transplantation From Family Haploidentical Donors in Patients With Myelodysplastic Syndrome and Acute Leukemia Under Primary Prophylaxis With Posaconazole
We'll reach out to this number within 24 hrs