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Myeloid MalignanciesPhase 2GITMO-PHYLOSNCT03270748

Post Transplant High-Dose Cy as GvHD Prophylaxis in 1 HLA Mismatched Unrelated HSCT for Myeloid Malignancies

A Phase 2 study testing GvHD prophylaxis in people with Myeloid Malignancies, run by Gruppo Italiano Trapianto di Midollo Osseo at 33 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The experimental treatment consists in the application of a therapeutic strategy with post Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving 1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Stem Cell Transplantation for Myeloid Malignancies. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Myeloid Malignancies
What is being tested?
GvHD prophylaxis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
33 sitesItaly
Study dates
15 Jan 2020to 20 Nov 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Acute myeloid leukemia in complete remission Myelodysplastic syndrome Indication for allo-HCT No available HLA identical sibling donor or HLA matched unrelated donor Activation of an alternative donor search Presence of a 1 antigen/allele mismatched (7/8 HLA matched) unrelated donor ECOG performance status <2 Written and signed informed consent

Who cannot join

  • left ventricular ejection fraction < 40% FEV1, FVC, DLCO <50% of predicted LFT > 5 times the upper limit of normal creatinine clearance < 40 ml/min Previous allogeneic Hemopoietic Stem Cell Transplantation

Trial locations and contacts

33 sites in 1 country.

33 sites in 1 country

Italy33 sites

  • Azienda Ospedaliera SS Antonio e Biagio

    Alessandria

  • Ospedali Riuniti

    Ancona

  • Ospedale Moscati

    Avellino

  • Policlinico di Bari-Ematologia con trapianti

    Bari

  • Divisione di Ematologia - Ospedali Papa Giovanni XXIII

    Bergamo

  • Ospedale San Orsola

    Bologna

  • Ospedale Regionale Generale- Divisione Ematologia

    Bolzano

  • ASST Spedali Civili

    Brescia

  • Ospedale Binaghi

    Cagliari

  • S.C. Ematologia - Azienda Ospedaliera S. Croce e Carle

    Cuneo

  • Ematologia e Centro Trapianti Midollo Osseo - Ospedale IRCCS Casa Sollievo della Sofferenza

    Foggia

  • AOU-IRCCS San Martino-IST

    Genova

  • Osp. Card. Panico

    Lecce

  • AOU Integrata

    Mestre

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

    Milan

  • Ospedale Niguarda Ca' Grande

    Milan

  • Divisione Ematologia - Azienda Ospedaliera Universitaria - Policlinico -

    Modena

  • ASST Ospedale S. Gerardo de' i Tintori - Università degli Studi di Milano

    Monza

  • A.O.U. Policlinico Federico II

    Naples

  • Azienda ospedaliera Universitaria di Parma

    Parma

  • Fondazione IRCCS San Matteo

    Pavia, 27100

  • Ospedale G. Da Saliceto di Piacenza

    Piacenza

  • Azienda Ospedaliero Universitaria Pisana

    Pisa

  • Centro Unico Regionale Trapianti di Midollo Osseo - Ospedale Bianchi-Melacino-Morelli

    Reggio Calabria

  • A.O. San Camillo Forlanini

    Roma

  • Divisione di Ematologia - Istituto di Semeiotica Medica - Policlinico A. Gemelli

    Roma

  • Policlinico Umberto I

    Roma

  • Az. Ospedaliera Universitaria Senese - Divisione Ematologia e Trapianti

    Siena

  • Ospedale Moscati

    Taranto

  • A.O.U. Citta della Salute e della Scienza

    Torino

  • Ospedale Gonzaga

    Torino

  • A.O. Santa Maria della Misericordia

    Udine

  • Ospedale S. Bortolo-Divisione Ematologia

    Vicenza

Other trials in Italy

About this study

Official title: Post Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving 1-Antigen/Allele HLA Mismatched (7/8 Matched) Unrelated Hemopoietic Stem Cell Transplantation for Myeloid Malignancies

The experimental treatment consists in the application of a therapeutic strategy with post Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving 1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Stem Cell Transplantation for Myeloid Malignancies.

Read the detailed description

The experimental treatment consists in the application of a therapeutic strategy with post Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving 1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Stem Cell Transplantation for Myeloid Malignancies Allogeneic hematopoietic stem cell transplantation is a potentially curative therapy for a variety of hematologic malignancies due to two separate components: chemo/radiotherapy administered before the transplant (conditioning regimen) and the presence of immunocompetent cells in the graft, capable of inducing a "graft-versus-malignancy effect" also known as "GvL" effect. However, this immune-reaction usually carries the risk of detrimental effects seen as a multi-organ syndrome known as graft-versus-host disease (GvHD), which remains the most feared complication of Allogeneic hematopoietic stem cell transplantation. GvHD may be given to disparities between donor and recipient in presence of gene mismatches in the Major Histocompatibility Complex, also known as Human Leucocyte Antigen (HLA) system, or in any minor histocompatibility antigen. Thus, GvHD is obviously more common (and possibly more severe) in patients transplanted from HLA-mismatched donors as compared with those receiving grafts from HLA-matched donors.

A major limitation of allo-HSCT is the availability of a donor given that only a small percentage of patients has a HLA identical family donor. For the majority of patients (approximately 70%) who lack a HLA-identical sibling, alternative donors include HLA-matched unrelated donors and cord blood units. The chance of identifying a suitable marrow unrelated donor (MUD) in the international voluntary donor registries is limited by the frequency of a certain HLA genotype in the general population.

One of the alternative options in such cases is the use of a HLA-mismatched unrelated donor (MMUD). HLA-mismatching is defined as the presence of unshared antigens/alleles in recipient-donor pairs for HLA-A, -B, -C or DRB1 loci.

Patients undergoing MUD or MMUD transplants usually receive an intensified three-drug immunosuppressive regimen: anti-thymocyte globulin in addition to the standard platform of a calcineurine-inhibitor and an anti-metabolite.

The effect of HLA mismatches on clinical outcomes has been investigated in several studies. Single HLA mismatches at HLA-A, -B, -C, or -DRB1 locus (7/8 HLA-matched) were associated with lower overall survival and disease free survival, higher non-relapse mortality, and higher incidence of acute GvHD as compared with 8/8 HLA-matched pairs.

Many clinical trials suggest that high-dose Cy administrated after allogeneic HSCT didn't cause prolonged aplasia due toxicity on donor stem cells; could prevent rejection due to HLA-disparity and could be effective in preventing GvHD, allowing adequate immune-reconstitution.

With this study the investigators plan to investigate if post-transplant high-dose Cy, with a calcineurine inhibitor and mycophenolate, could reduce acute GvHD rates and infectious complications improving clinical outcomes of MMUD transplants in patients with acute myeloid leukemia and myelodysplastic syndrome.

Being tested
GvHD prophylaxis
Keywords
Allogeneic hematopoietic stem cell transplantation, acute graft-versus-host disease, Unrelated donors, Post-transplant cyclophosphamide, Myeloid Malignancies, unrelated hematopoietic cell transplantation, GITMO

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GvHD prophylaxisDrug

    Cyclophosphamide 50 mg/kg intravenously day+3 and +4 (total dose:100 mg/kg).

Study groups in NCT03270748
Study groupRoleWhat they receive
ExperimentalExperimentalExperimental: Experimental The experimental consists in the application of a therapeutic strategy: post Transplant High-Dose Cyclophosphamide as GvHD Prophylaxis in Patients Receiving 1-Antigen/Allele HLA Mismatched (7/8 matched) Unrelated Hemopoietic Stem Cell Transplantation for Myeloid Malignancies Therapeutic intervention, namely conditioning regimen and GVHD prophylaxis, are based on standard current regimens: Busulfan 0,8 mg/kg 4 times per day during 2 h infusions for 4 consecutive days (from day -6 through day -3) Fludarabine 40 mg/m2 per day for 4 days (from day -6 through day -3); GvHD prophylaxis: Cyclosporine or Tacrolimus beginning day+5 up to at least 100 days. Micofenolate 15mg/kg twice a day from day +5 to +35.
Receives: Drug: GvHD prophylaxis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. incidence of acute GvHD

    cumulative incidence of acute GvHD (grade II-IV) at 100 days post Unrelated Hemopoietic Stem Cell Transplantation

    Measured: day +100 post-transplant

Secondary outcomes (8)

  1. Overall survival

    is defined as the time from transplant to the date of death due to any cause or to the last date the patient was known to be alive (censored observation) or to the date of the data cut-off for final analysis

    Measured: 1 year post transplantation

  2. GRFS (GvHD free, relapse free survival)

    are defined as occurrence of grade III-IV acute GvHD, chronic GvHD requiring systemic immunosuppressive treatment, disease relapse, or death from any cause

    Measured: first 12 months after transplantation

  3. chronic graft-versus-host disease

    Cumulative incidence and severity of chronic graft-versus-host disease (by NIH criteria)

    Measured: 3 years from transplantation

  4. Graft failure

    failure a) Primary graft failure is defined as < 5% donor chimerism. Secondary graft failure (graft rejection) is defined as initial recovery followed by neutropenia with <5% donor chimerism. b) Rate of graft rejection and graft failure

    Measured: day +100 and 1 year after transplantation

  5. Haematopoietic Recovery

    Time to reach an absolute neutrophil count > 0.5 109/L from day of HSCT. Neutrophil recovery end-point will be defined as the first of 3 consecutive days with an absolute neutrophil count > 0.5 x109/L. Time to reach platelet engraftment, defined as the number of days after HSCT (Day 0) for patients to maintain an un-transfused platelet count of > 20.0 x 109/L.

    Measured: participants will be followed for the duration of hospital stay, an expected average of 30 days

  6. Non Relapse Mortality

    The cumulative incidence of Non Relapse Mortality is defined as death due to any other cause than progression of malignancy after allogeneic stem cell transplantation. Cumulative incidence

    Measured: at 100 days, at 180days and at 1 year from transplantation

  7. Relapse and Residual Disease

    Testing for recurrent malignancy in the blood, marrow or other sites will be used to assess relapse after transplantation. For the purpose of this study, relapse is defined by either morphological or cytogenetic evidence of acute myeloid leukemia or myelodisplastic syndrome consistent with pre-transplant features. Molecular relapse will be defined where available as any evidence of a pre-transplant defined abnormality using conventional cytogenetics or FISH techniques or cytofluorimetric analysis or molecular probes

    Measured: at 1 year from transplantation

  8. Incidence of infectious complications and kinetics of immune-reconstitution

    the rate of proven and probable invasive fungal infections and viral reactivation/disease (CMV, HHV6,Adenovirus, EBV). Immune-reconstitution will be evaluated with lymphocyte sub-populations counts (CD3+, CD4+, CD8+, CD16+, CD20+) and IgG, IgA, IgM titer

    Measured: one year after transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Sep 2017
  2. Study start15 Jan 2020
  3. Primary completion20 Nov 2022
  4. Study completion20 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03270748
Sponsor's protocol ID
GITMO-PHYLOS
Acronym
GITMO-PHYLOS
Status last verified
Mar 2023
First submitted
24 Aug 2017
Last updated
10 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Raiola AM, Bruno B, Risitano AM, Mosna F, Cavattoni IM, Onida F, Saporiti G, Patriarca F, Battista ML, Pavone V, Mele A, Chiusolo P, Sica S, Loteta B, di Grazia C, Carella AM, Salvatore D, Morello E, Leoni A, Giaccone L, Bernasconi P, Terruzzi E, Mordini N, Borghero C, Zallio F, Luppi M, Grassi A, Olivieri A, Piras E, Sacchi N, Ciccone G, Castiglione A, Degrandi E, Angelucci E, Martino M, Bonifazi F. Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial. Blood Adv. 2025 Apr 22;9(8):1966-1975. doi: 10.1182/bloodadvances.2024015173.

    PubMed 39928954

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GvHD prophylaxis in people with Myeloid Malignancies, run by Gruppo Italiano Trapianto di Midollo Osseo at 33 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

incidence of acute GvHD (time frame: day +100 post-transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03270748, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2023.

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