MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study

Phase 1

Withdrawn

• Conditions: Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
• Interventions: Biological: Hematopoietic Allogeneic Stem Cells

• Registration Number: NCT02427178
• Lead Sponsor: Michio Hirano, MD

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-02-10
• Study Start: 2015-03
• Study First Submitted QC: 2015-04-22
• Study First Posted: 2015-04-27
• Primary Completion: 2022-06
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-28
• Last Update Posted: 2022-08-01
• Study Completion: 2023-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open label	Hematopoietic Allogeneic Stem Cells	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.

Primary Outcome Measures

Name	Time	Method
neutrophil count (cells/L)	42 days	engraftment success

Secondary Outcome Measures

Name	Time	Method
chimerism percentage	100 days	percent of donor cell chimerism at 100 days
micromole Thd	100 days	level of thymidine
number of patient survival days	100 days	is the patient al
micromole/l dUrd	100 days	level of deoxyuridine