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

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ClinicalTrials.gov Identifier: NCT03434704
Recruitment Status : Recruiting
First Posted : February 15, 2018
Last Update Posted : September 9, 2019
Sponsor:
Information provided by (Responsible Party):
Ciceri Fabio, IRCCS San Raffaele

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.


Condition or disease Intervention/treatment Phase
Transplant-Related Hematologic Malignancy Leukemia, Acute Myelodysplastic Syndromes Graft Vs Host Disease Fungal Infection Drug: Conditioning treatment "Thiotepa-Treosulfan-Fludarabine" Procedure: PBSC graft Drug: GvHD prophylaxis Drug: Primary antifungal prophylaxis Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 82 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : June 18, 2018
Estimated Primary Completion Date : March 15, 2020
Estimated Study Completion Date : September 15, 2022


Arm Intervention/treatment
Experimental: Single Arm Treatment
Conditioning treatment "Thiotepa-Treosulfan-Fludarabine"; PBSC graft; GvHD prophylaxis; Primary antifungal prophylaxis.
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.
Other Name: TTF

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.


Drug: 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.




Primary Outcome Measures :
  1. Graft-versus-host disease-free, relapse-free survival (GRFS) [ Time Frame: 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 Outcome Measures :
  1. Efficacy of antifungal prophylaxis strategy [ Time Frame: 85 days after transplantation ]
    The rate of proven, probable and possible invasive fungal diseases documented within the first 85 days after transplantation



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03434704


Contacts
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Contact: Fabio Ciceri, MD 0039022643 ext 4289 ciceri.clinicaltrials@hsr.it

Locations
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Italy
Ospedale San Raffaele Recruiting
Milano, Lombardia, Italy, 20132
Contact: Fabio Ciceri, MD    0039022643 ext 4289    ciceri.clinicaltrials@hsr.it   
Sub-Investigator: Raffaella Greco, MD         
Sub-Investigator: Jacopo Peccatori, MD         
Sub-Investigator: Maria Teresa Lupo Stanghellini, MD         
Sub-Investigator: Andrea Assanelli, MD         
Sub-Investigator: Consuelo Corti, MD         
Sponsors and Collaborators
Ciceri Fabio

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Responsible Party: Ciceri Fabio, MD, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT03434704     History of Changes
Other Study ID Numbers: 2017-004423-78
First Posted: February 15, 2018    Key Record Dates
Last Update Posted: September 9, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mycoses
Leukemia
Preleukemia
Myelodysplastic Syndromes
Graft vs Host Disease
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Immune System Diseases
Miconazole
Posaconazole
Antifungal Agents
Fludarabine
Fludarabine phosphate
Thiotepa
Treosulfan
Busulfan
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Infective Agents