NCT03434704

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jun 2018

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 9, 2018

Completed
6 days until next milestone

First Posted

Study publicly available on registry

February 15, 2018

Completed
4 months until next milestone

Study Start

First participant enrolled

June 18, 2018

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 13, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 13, 2019

Completed
Last Updated

July 19, 2022

Status Verified

July 1, 2022

Enrollment Period

1.3 years

First QC Date

February 9, 2018

Last Update Submit

July 18, 2022

Conditions

Transplant-Related Hematologic MalignancyLeukemia, AcuteMyelodysplastic SyndromesGraft Vs Host DiseaseFungal Infection

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • Efficacy of antifungal prophylaxis strategy

    85 days after transplantation

Study Arms (1)

Single Arm Treatment

EXPERIMENTAL

Conditioning treatment "Thiotepa-Treosulfan-Fludarabine"; PBSC graft; GvHD prophylaxis; Primary antifungal prophylaxis.

Drug: Conditioning treatment "Thiotepa-Treosulfan-Fludarabine"Procedure: PBSC graftDrug: GvHD prophylaxisDrug: Primary antifungal prophylaxis

Interventions

Conditioning treatment "Thiotepa-Treosulfan-Fludarabine"DRUG

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.

Also known as: TTF
Single Arm Treatment
PBSC graftPROCEDURE

(target 4-8 × 106 CD34+ cells/kg patient body weight)

Single Arm Treatment
GvHD prophylaxisDRUG

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.

Single Arm Treatment
Primary antifungal prophylaxisDRUG

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.

Single Arm Treatment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

Location

MeSH Terms

Conditions

LeukemiaMyelodysplastic SyndromesGraft vs Host DiseaseMycoses

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow DiseasesImmune System DiseasesBacterial Infections and MycosesInfections

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

February 9, 2018

First Posted

February 15, 2018

Study Start

June 18, 2018

Primary Completion

October 13, 2019

Study Completion

October 13, 2019

Last Updated

July 19, 2022

Record last verified: 2022-07

Locations

IT(1)