MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study

Study Overview
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Brief Summary
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The purpose of this study is to find out if a stem cell transplant is safe for patients with a very rare disease. The stem cell transplant is called AHSCT (for allogeneic hematopoetic stem cell transplantation). The rare disease is called MNGIE (for Mitochondrial NeuroGastroIntestinal Encephalomyopathy). Patients with MNGIE will be transplanted with stem cells from an individual who is human leukocyte antigen (HLA) 10/10 matched. The purpose of the transplant is the production of thymidine phosphorylase.

Detailed Description
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Patients who have been identified as having MNGIE by genetic testing and/or reduced thymidine phosphorylase levels will be considered for this study. The study team physician will evaluate the condition of the patient and determine if they are eligible. An HLA matched donor is necessary for transplantation. If a suitable donor is found the transplant process can proceed. The patient receives immunosuppressive therapy ( 1 week in the hospital) with subsequent IV transfer of stem cells from the donor. The patient remains in the hospital for approximately 1 month to monitor the transplant. The patient is required to attend research visits at days 0, 100, 6m, 18m and 24 m.

Official Title
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MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) AHSCT (Allogeneic Hematopoietic Stem Cell Transplant) Safety Study

Conditions
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Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)

Intervention / Treatment
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* Biological: Hematopoietic Allogeneic Stem Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Homozygous or compound heterozygous mutations in the TYMP gene Plasma thymidine level >3micromole/L Plasma deoxyuridine >7.5 micromole/L 5 to 55 years of age Appropriate stem cell donor (HLA 10/10 matched) Karnofsky performance of at least 55 Exclusion Criteria: Severe cognitive impairment Severe psychiatric illness Moderate to severe lung disease Prior episode of peritonitis due to perforated diverticula Prior episode of intestinal pseudo-obstruction Moderate to severe hepatopathy Moderate to severe diabetes Mellitus Moderate to severe cardiomyopathy Moderate to severe nephropathy Pregnancy or planning to become pregnant during study Hypersensitivity to E.coli derived products HIV disease Positive to anti-donor HLA DP

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open label<br>Hematopoietic allogeneic stem cells will be transplanted: HLA testing will be performed on potential stem cell donors. HLA 10/10 matched donors are eligible, however there are additional criteria that will be applied to determine an acceptable donor. Patients will receive 2 X10 6 CD34 cells/kg weight. | Biological: Hematopoietic Allogeneic Stem Cells<br>* HLA 10/10 matched allogeneic bone marrow cells will be infused into recipient (patient).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| neutrophil count (cells/L) | engraftment success | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patient survival days | is the patient al | 100 days | 
| chimerism percentage | percent of donor cell chimerism at 100 days | 100 days | 
| micromole/l dUrd | level of deoxyuridine | 100 days | 
| micromole Thd | level of thymidine | 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MNGIE, Allogeneic Hematopoietic Stem Cell Transplantation, Stem Cell transplant