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Completed

NCT Number: NCT02582775

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

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).

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Key information

Conditions

Epidermolysis Bullosa Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Skin Abnormalities Skin Diseases Skin Diseases, Genetic Skin Diseases, Vesiculobullous Skin and Connective Tissue Diseases

Age range

Up to 25 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Minnesota Masonic Cancer Center and Medical Center

Minneapolis, Minnesota, 55455, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • 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

Exclusion criteria

  • 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.

Treatment and study plan

Thymoglobulin

Drug

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

Other names: ATG, anti-thymocyte globulin

Cyclophosphamide

Drug

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

Other names: Cytoxan

Fludarabine

Drug

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

Other names: fludarabine phosphate, Fludara

Total Body Irradiation

Radiation

See arm description for dosing.

Other names: TBI

Bone marrow infusion

Procedure

Bone marrow infusion on Day 0

Other names: HCT

Tacrolimus

Drug

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.

Other names: Prograf

Mycophenolate mofetil

Drug

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

Other names: MMF

Donor mesenchymal stem cell infusions

Biological

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

busulfan

Drug

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

Primary outcomes

  1. Event-free Survival

    Time frame: 1 year post-transplant

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

Secondary outcomes

  1. Change of a Patient's iscorEB

    Time frame: 1 year post-transplant

    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.

  2. Transplant-related Mortality

    Time frame: 180 days post-transplant

    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.

  3. Average Change in Quality of Life

    Time frame: 1 year post-transplant

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

  4. Average Change in Quality of Life

    Time frame: 2 years post-transplant

    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.

  5. Lymphoid Chimerism

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

    Median hematopoietic cells that are of donor origin per participant.

  6. Myeloid Chimerism

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

    Median hematopoietic cells that are of donor origin per participant.

  7. Average Change of a Patient's iscorEB

    Time frame: 2 year post-transplant

    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.

Sponsors and collaborators

Lead sponsor

Masonic Cancer Center, University of Minnesota

Other

Registry information

Official study title

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

Important dates

Study start
2016
Primary completion
2022
Study completion
2023
First posted
Oct 21, 2015
Registry last updated
Sep 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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