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Epidermolysis BullosaPhase 2NCT02582775

MT2015-20: Biochemical Correction of Severe EB by Allo HSCT and Serial Donor MSCs

A Phase 2 study testing Thymoglobulin, Cyclophosphamide and Fludarabine in people with Epidermolysis Bullosa, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

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

This is a single-institution, phase II study to determine the event-free survival at 1 year post allogeneic transplant and serial mesenchymal stem cell (MSC) infusions from a related donor (HLA identical, mismatched or haploidentical) or matched unrelated donor for the biochemical correction of severe epidermolysis… Read more about this study

Who is it for?
Ages Up to 25 years
Conditions the study is for
Epidermolysis Bullosa
What is being tested?
Thymoglobulin, Cyclophosphamide and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteUnited States
Study dates
Mar 2016to 26 Jul 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Diagnosis of severe form of EB characterized by collagen, laminin, integrin, keratin or plakin deficiency (by immunofluorescence staining with protein specific antibodies or Western blotting and by mutation analysis).
  • Adequate organ function within 4 weeks of study registration defined as:
  • Renal: glomerular filtration rate within normal range for age
  • Hepatic: Hepatic: bilirubin, AST/ALT, ALP < 5 x upper limit of normal
  • Pulmonary: adequate pulmonary function in the opinion of the enrolling investigator
  • Cardiac: left ventricular ejection fraction ≥ 45%, normal EKG or approved by Cardiology for transplant
Show all 9Show fewer
  • Sexually active participants must agree to use adequate birth control for the during the study period (from before the start of the preparative chemotherapy through 1 year post-transplant)
  • Available donor per section 5: targeted MFI < 1,000 (MFI exceeding 1000 must be approved by the PI and treatment team.)
  • Voluntary written consent - adult or parent (with information sheet for minors, if applicable) prior to any research related procedures or treatment

Who cannot join

  • beta 3 laminin JEB mutants
  • Active untreated systemic infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days)
  • History of HIV infection
  • Evidence of squamous cell carcinoma
  • Pregnant or breast feeding. Females of child-bearing potential must have a negative pregnancy test prior to study registration as the agents administered in this study are Pregnancy Category C and D.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Minnesota Masonic Cancer Center and Medical Center

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: MT2015-20: Biochemical Correction of Severe Epidermolysis Bullosa by Allogeneic Cell Transplantation and Serial Donor Mesenchymal Cell Infusions

This is a single-institution, phase II study to determine the event-free survival at 1 year post allogeneic transplant and serial mesenchymal stem cell (MSC) infusions from a related donor (HLA identical, mismatched or haploidentical) or matched unrelated donor for the biochemical correction of severe epidermolysis bullosa (EB).

Being tested
Thymoglobulin, Cyclophosphamide, Fludarabine, Total Body Irradiation, Bone marrow infusion
Medical subject headings
Epidermolysis Bullosa

What participants receive

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

  • ThymoglobulinDrug

    Also called ATG, anti-thymocyte globulin

    0.5 mg/kg IV over 6 hours on day -9 and 2 mg/kg IV over 4 hours on day -8 and day -7 with premeds and solumedrol through day -2

  • CyclophosphamideDrug

    Also called Cytoxan

    14.5 mg/kg IV over 1 hour day -6 and -5 50 mg/kg IV over 2 hours with mesna 40 mg/kg IV day +2 and +3

  • FludarabineDrug

    Also called fludarabine phosphate, Fludara

    30 mg/m2 IV over 60 minutes days -6 through day -2

  • Total Body IrradiationRadiation

    Also called TBI

    See arm description for dosing.

  • Bone marrow infusionProcedure or surgery

    Also called HCT

    Bone marrow infusion on Day 0

  • TacrolimusDrug

    Also called Prograf

    Day +5 through day +100 with goals of 5-10 ug/L (not used for HLA-identical related donors). When used in non-MSD recipients, tapered over 6-8 weeks starting at day +100.

  • Mycophenolate MofetilDrug

    Also called MMF

    15 mg/kg IV q8h (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams. Day +5 through day 35

  • Donor mesenchymal stem cell infusionsBiological

    Day 60, 100 and 180 (collected during donor BM harvest for graft)

  • BusulfanDrug

    busulfan IV over 3 hours on days -3 and -2 for HLA-mismatched BM recipients only (Arms F and G)

Study groups in NCT02582775
Study groupRoleWhat they receive
RDEB: HCT plus MSC Arm BExperimentalRecessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
Receives: Drug: Thymoglobulin; Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total Body Irradiation; Procedure: Bone marrow infusion; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Biological: Donor mesenchymal stem cell infusions
JEB: HCT plus MSC Arm BExperimentalJunctional epidermolysis bullosa (JEB) patient treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (300 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
Receives: Drug: Thymoglobulin; Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total Body Irradiation; Procedure: Bone marrow infusion; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Biological: Donor mesenchymal stem cell infusions
RDEB: HCT Plus MSC Arm EExperimentalRecessive dominant epidermolysis bullosa (RDEB) patients treated per study regimen on a post-transplant cyclophosphamide allogeneic hematopoietic cell transplant (HCT) platform conditioned with reduced intensity chemotherapy and low dose total body irradiation (400 cGy), followed post-HCT by serial infusions of donor-derived mesenchymal stromal cells (MSC).
Receives: Drug: Thymoglobulin; Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total Body Irradiation; Procedure: Bone marrow infusion; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Biological: Donor mesenchymal stem cell infusions
HCT with 300 cGy of TBI Arm AExperimentalEpidermolysis bullosa patients treated per study regimen with chemotherapy and stem cell transplant without mesenchymal stem cell infusions.
Receives: Drug: Thymoglobulin; Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total Body Irradiation; Procedure: Bone marrow infusion; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Biological: Donor mesenchymal stem cell infusions
Re-Transplant Arm CExperimentalEpidermolysis bullosa patients treated regardless of original transplant arm with re-transplant using 300 cGy of TBI.
Receives: Drug: Thymoglobulin; Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total Body Irradiation; Procedure: Bone marrow infusion; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Biological: Donor mesenchymal stem cell infusions
HCT Arm DExperimentalHLA-matched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGY BID of TBI (400 cGy total).
Receives: Drug: Thymoglobulin; Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total Body Irradiation; Procedure: Bone marrow infusion; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Biological: Donor mesenchymal stem cell infusions
HCT Alone Arm FExperimentalHLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant alone using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
Receives: Drug: Thymoglobulin; Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total Body Irradiation; Procedure: Bone marrow infusion; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Biological: Donor mesenchymal stem cell infusions; Drug: Busulfan
HCT plus MSC Arm GExperimentalHLA-mismatched epidermolysis bullosa patients treated with hematopoietic cell transplant plus serial MSC infusions using 200 cGy BID of TBI (400 cGy total) + addition of low dose busulfan for recipients of HLA-mismatched bone marrow
Receives: Drug: Thymoglobulin; Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total Body Irradiation; Procedure: Bone marrow infusion; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Biological: Donor mesenchymal stem cell infusions; Drug: Busulfan

What is being measured

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

  1. Event-free Survival

    An event defined as death or a 50% increase in a patient's IScoreEB from baseline

    Measured: 1 year post-transplant

Secondary outcomes (7)
  1. Change of a Patient's iscorEB

    iscorEB surveys are a validated, standard of care tool used to assess disease status in patients with Epidermolysis Bullosa. Measure changes in quality of life (QOL) through pain, itching, and general QOL IScorEB questionnaire. Scores can range from 16 to 112. The QOLS scores are summed so that a higher score indicates higher quality of life.

    Measured: 1 year post-transplant

  2. Transplant-related Mortality

    Cumulative incidence will be used to estimate the probability of relapse treating non-relapse death as a competing risk and transplant-related mortality conversely treating relapse as a competing risk.

    Measured: 180 days post-transplant

  3. Average Change in Quality of Life

    Measured by the Lansky or Karnofsky score (10-100). Higher scores indicate a better outcome. Midpoint of change in scores used to indicate median.

    Measured: 1 year post-transplant

  4. Average Change in Quality of Life

    Measured by the Lansky or Karnofsky score (10-100). The Karnofsky Performance Scale is an assessment tool intended to gauge a patient's functional status and ability to carry out activities of daily living. Higher scores indicate a better outcome. Midpoint of change in scores used to indicate median.

    Measured: 2 years post-transplant

  5. Lymphoid Chimerism

    Median hematopoietic cells that are of donor origin per participant.

    Measured: Day 28, 60, 100, 180, and year 1 and 2 post-transplant

  6. Myeloid Chimerism

    Median hematopoietic cells that are of donor origin per participant.

    Measured: Day 28, 60, 100, 180, and year 1 and 2 post-transplant

  7. Average Change of a Patient's iscorEB

    iscorEB surveys are a validated, standard of care tool used to assess disease status in patients with Epidermolysis Bullosa. Measure percent of changes in quality of life (QOL) through pain, itching, and general QOL IScorEB questionnaire. Scores can range from 16 to 112. The QOLS scores are summed so that a higher score indicates higher quality of life.

    Measured: 2 year post-transplant

Timeline

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

  1. First posted21 Oct 2015 (estimated)
  2. Study startMar 2016
  3. Primary completion15 Nov 2022
  4. Study completion26 Jul 2023

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02582775
Sponsor's protocol ID
2015LS076
Status last verified
Aug 2024
First submitted
16 Oct 2015
Last updated
19 Sep 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Ebens CL, McGrath JA, Tamai K, Hovnanian A, Wagner JE, Riddle MJ, Keene DR, DeFor TE, Tryon R, Chen M, Woodley DT, Hook K, Tolar J. Bone marrow transplant with post-transplant cyclophosphamide for recessive dystrophic epidermolysis bullosa expands the related donor pool and permits tolerance of nonhaematopoietic cellular grafts. Br J Dermatol. 2019 Dec;181(6):1238-1246. doi: 10.1111/bjd.17858. Epub 2019 Jun 28.

    PubMed 30843184

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Thymoglobulin, Cyclophosphamide and Fludarabine in people with Epidermolysis Bullosa, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

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 9 inclusion and 5 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 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Event-free Survival (time frame: 1 year 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 NCT02582775, 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 19 Sep 2024.

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