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Hematologic MalignanciesPhase 1/2PTC-UC-MSCNCT02032446

Umbilical Cord Derived Mesenchymal Stromal Cells For The Treatment of Severe Steroid-resistant Graft Versus Host Disease

A Phase 1/2 study testing UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC) in people with Hematologic Malignancies, run by A.O. Ospedale Papa Giovanni XXIII at 8 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

MESENCHYMAL STROMAL CELLS (MSC) have shown promising albeit not always consistent therapeutic effects in the treatment of severe steroid-resistant acute Graf versus Host Disease. Read more about this study

Who is it for?
Ages Up to 70 years
Conditions the study is for
Hematologic Malignancies
What is being tested?
UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
8 sitesItaly
Study dates
Sep 2013to Sep 2019
Phase
Phase 1/2
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 Up to 70 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients are required to meet the following inclusion criteria:
  • Patients with steroid refractory grade III-IV classic acute graft versus host disease (GvHD)occurring within 100 days after transplant or induced by donor lymphocyte infusions (DLI) or T-cell add back. Steroid refractory graft versus host disease (GvHD)is defined according to Pidala and Anasetti10 as follows: a) progression of at least 1 overall grade within 3 days of optimal steroid treatment; b) failure to demonstrate any overall grade improvement over 5 to 7 days; c) incomplete response by 14 days of 2 mg/kg/day of steroid therapy.
  • Patients with persistent, recurrent, or late acute graft versus host disease (GvHD) (features of acute graft versus host disease occurring beyond 100 days, often during withdrawal of immune suppression).
  • Patients with an overlap syndrome in which diagnostic or distinctive features of chronic graft versus host disease (GvHD) and acute graft versus host disease (GvHD) appear together79.

Who cannot join

  • 1. Inability to obtain written informed consent

Trial locations and contacts

8 sites in 1 country.

ALESSANDRO RAMBALDI, MD contact

035.2673681 ext. 0039

arambaldi@asst-pg23.it

8 sites in 1 country

Italy8 sites, 6 recruiting

  • A O Papa Giovanni XXIII

    Bergamo, 24127

    Maria Luisa Ferrari, Study coordinator, 035.2673681 ext. 0039, mlferrari@asst-pg23.it

    Alessandra Algarotti, MD

    Recruiting

  • Ao S Croce E Carle

    Cuneo, 12100

    NICOLA MORANDINI, MD, +3901716424478, MORANDININ@GMAIL.COM

    Recruiting

  • AO Careggi

    Florence, 50134

    Riccardo Saccardi, MD, 0557947672, riccardo.saccardi@aou.unifi.it

    Not yet recruiting

  • IRCCS G Gaslini

    Genova, 16147

    Edoardo Lanino, MD, 01056362405, edoardolanino@gaslini.org

    Not yet recruiting

  • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

    Milan, 20122

    Active, not recruiting

  • Clinica Pediatrica San Gerardo

    Monza, 20900

    Active, not recruiting

  • Azienda Ospedaliero-Universitaria Di Udine

    Udine, 33100

    RENATO FANIN, MD, +39.0432559662, RENATO.FANIN@UNIUD.IT

    Not yet recruiting

  • Ospedale San Bortolo

    Vicenza, 36100

    ROBERTO RAIMONDI, MD, +39.0444753518, RAIMONDI@HEMATO.VEN.IT

    Recruiting

Other trials in Italy

About this study

Official title: UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC) FOR THE TREATMENT OF SEVERE (GRADE III-IV) STEROID-RESISTANT GRAFT VERSUS HOST DISEASE (GvHD): A PHASE I/II TRIAL

MESENCHYMAL STROMAL CELLS (MSC) have shown promising albeit not always consistent therapeutic effects in the treatment of severe steroid-resistant acute Graf versus Host Disease. Remarkably, in all reported clinical studies the toxicity of Mesenchymal stromal cells administration has been found consistently negligible. The investigators believe that Umbilical Cord (UC) derived Mesenchymal stromal cells may represent a stronger immunosuppressive tool for such clinical emergency and no data suggest any change in the safety profile of these cells. For this reason, and in the best interest of the patient, the investigators plan to test the safety and activity of Umbilical Cord Mesenchymal stromal cells when given sequentially to another partially effective treatment of steroid resistant acute graf versus host disease such as Pentostatin.

Being tested
UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC)
Medical subject headings
Hematologic Neoplasms

What participants receive

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

  • UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC)Biological

    pentostatin, dose 1 mg/m2

    § MSC doses:

    1. 3 patients → 3 infusions of 1x106 cells /kg
    2. 3 patients → 3 infusions of 2x106 cells /kg
    3. 3 patients → 3 infusions of 3x106 cells /kg
Study groups in NCT02032446
Study groupRoleWhat they receive
Umbilical Cord Mesenchymal stromal cells (UC-MSC)ExperimentalPentostatin will be given by intravenous infusion at a dose of 1 mg/m2 for 3 consecutive days. Thereafter, three Umbilical Cord Mesenchymal stromal cells (UC-MSC) infusions will be given at weekly interval starting from day 5. We will follow a dose escalating programme with progressively increasing doses of cells until the maximally tolerated dose (MTD) is achieved. The dose escalating design will be characterised by the administration of 1x106 /kg UC-MSC per dose per three doses for the first three patients (total up to 3x106/kg). The second three patients will receive 2x106/kg UC-MSC per dose per three doses (total up to 6x106/kg). The third three patients will receive 3x106/kg UC-MSC per dose per three doses (total up to 9x106 cells/kg). Since three dosages of cells are programmed for each group of 3 patients, a minimum of 9 patients should be studied, unless unacceptable acute infusion related toxicity is observed.
Receives: Biological: UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC)

What is being measured

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

  1. vital parameters

    Following infusion of UC-MSC, the patient will be monitored for acute infusion-related toxicity. Any toxicity will be treated at the discretion of the attending physician. Infusional toxicity is defined as any alteration of the vital parameters of the patient if they have appeared acutely and may be directly correlated to the UC-MSC infusion

    Measured: one year

Secondary outcomes (1)

  1. assessed of acute graft versus host disease (GvHD)

    graft versus host disease will be assessed at day +7, +9, +12, +14, +16, +19, +21, +28, + 35, +42 e +49 and after 6 months and 1 year from the last UC-MSC infusion. Efficacy on acute graft versus host disease is defined as complete or partial resolution of acute GvHD evaluated according to conventional staging and grading score systems.The efficacy will be evaluated at day +30 after the third UC-MSC infusion or, if less, at day +30 after the last UC-MSC infusion.

    Measured: one year

Timeline

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

  1. First posted10 Jan 2014 (estimated)
  2. Study startSep 2013
  3. Primary completionSep 2016
  4. Study completionSep 2019 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02032446
Sponsor's protocol ID
EudraCT 2012-000582-21
Acronym
PTC-UC-MSC
Status last verified
Jan 2019
First submitted
4 Nov 2013
Last updated
18 Jan 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: interim analysis

Publications

  • Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O; Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008 May 10;371(9624):1579-86. doi: 10.1016/S0140-6736(08)60690-X.

    PubMed 18468541

  • Capelli C, Gotti E, Morigi M, Rota C, Weng L, Dazzi F, Spinelli O, Cazzaniga G, Trezzi R, Gianatti A, Rambaldi A, Golay J, Introna M. Minimally manipulated whole human umbilical cord is a rich source of clinical-grade human mesenchymal stromal cells expanded in human platelet lysate. Cytotherapy. 2011 Aug;13(7):786-801. doi: 10.3109/14653249.2011.563294. Epub 2011 Mar 18.

    PubMed 21417678

  • Lucchini G, Introna M, Dander E, Rovelli A, Balduzzi A, Bonanomi S, Salvade A, Capelli C, Belotti D, Gaipa G, Perseghin P, Vinci P, Lanino E, Chiusolo P, Orofino MG, Marktel S, Golay J, Rambaldi A, Biondi A, D'Amico G, Biagi E. Platelet-lysate-expanded mesenchymal stromal cells as a salvage therapy for severe resistant graft-versus-host disease in a pediatric population. Biol Blood Marrow Transplant. 2010 Sep;16(9):1293-301. doi: 10.1016/j.bbmt.2010.03.017. Epub 2010 Mar 27.

    PubMed 20350611

  • Ringden O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lonnies H, Marschall HU, Dlugosz A, Szakos A, Hassan Z, Omazic B, Aschan J, Barkholt L, Le Blanc K. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation. 2006 May 27;81(10):1390-7. doi: 10.1097/01.tp.0000214462.63943.14.

    PubMed 16732175

  • von Bonin M, Stolzel F, Goedecke A, Richter K, Wuschek N, Holig K, Platzbecker U, Illmer T, Schaich M, Schetelig J, Kiani A, Ordemann R, Ehninger G, Schmitz M, Bornhauser M. Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant. 2009 Feb;43(3):245-51. doi: 10.1038/bmt.2008.316. Epub 2008 Sep 29.

    PubMed 18820709

  • Perez-Simon JA, Lopez-Villar O, Andreu EJ, Rifon J, Muntion S, Diez Campelo M, Sanchez-Guijo FM, Martinez C, Valcarcel D, Canizo CD. Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial. Haematologica. 2011 Jul;96(7):1072-6. doi: 10.3324/haematol.2010.038356. Epub 2011 Mar 10.

    PubMed 21393326

  • Weiss ML, Anderson C, Medicetty S, Seshareddy KB, Weiss RJ, VanderWerff I, Troyer D, McIntosh KR. Immune properties of human umbilical cord Wharton's jelly-derived cells. Stem Cells. 2008 Nov;26(11):2865-74. doi: 10.1634/stemcells.2007-1028. Epub 2008 Aug 14.

    PubMed 18703664

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing UMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC) in people with Hematologic Malignancies, run by A.O. Ospedale Papa Giovanni XXIII at 8 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 4 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: status not confirmed, as of the sponsor's last update on 18 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Results are not available in the source record.

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

Contact ALESSANDRO RAMBALDI, MD (035.2673681 ext. 0039, arambaldi@asst-pg23.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

vital parameters (time frame: one year). 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 NCT02032446, which also lists 7 linked publications.

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 18 Jan 2019.

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