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

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.

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 Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes; Fungal Infection; Graft Vs Host Disease; Leukemia, Acute; Transplant-Related Hematologic Malignancy
• Intervention / Treatment: Drug: Conditioning treatment "Thiotepa-Treosulfan-Fludarabine"; Procedure: PBSC graft; Drug: GvHD prophylaxis; Drug: Primary antifungal prophylaxis

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • Ospedale San Raffaele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ciceri Fabio

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2018
• Primary Completion (Actual): October 13, 2019
• Study Completion (Actual): October 13, 2019

Study Registration Dates

• First Submitted: February 9, 2018
• First Submitted That Met QC Criteria: February 9, 2018
• First Posted (Actual): February 15, 2018

Study Record Updates

• Last Update Posted (Actual): July 19, 2022
• Last Update Submitted That Met QC Criteria: July 18, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Disease; Bone Marrow Diseases; Hematologic Diseases; Bacterial Infections and Mycoses; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Hematologic Neoplasms; Leukemia; Preleukemia; Mycoses; Graft vs Host Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Fludarabine; Antifungal Agents; Clotrimazole; Miconazole; Thiotepa; Treosulfan
• Other Study ID Numbers: 2017-004423-78

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No