MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) Clinical Trial

— MASS  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02427178
• Other study ID #: AAAI1718
• Secondary ID: U54NS078059
• Status: Withdrawn
• Phase: Phase 1
• Start date: March 2015
• Est. completion date: June 2023

Study information

• Verified date: July 2022
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT02363881

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2023
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)

Intervention

Biological:
• Hematopoietic Allogeneic Stem Cells
HLA 10/10 matched allogeneic bone marrow cells will be infused into recipient (patient).

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Michio Hirano, MD	Cornell University, National Institute of Neurological Disorders and Stroke (NINDS)

References & Publications (4)

Halter J, Schüpbach W, Casali C, Elhasid R, Fay K, Hammans S, Illa I, Kappeler L, Krähenbühl S, Lehmann T, Mandel H, Marti R, Mattle H, Orchard K, Savage D, Sue CM, Valcarcel D, Gratwohl A, Hirano M. Allogeneic hematopoietic SCT as treatment option for patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a consensus conference proposal for a standardized approach. Bone Marrow Transplant. 2011 Mar;46(3):330-337. doi: 10.1038/bmt.2010.100. Epub 2010 May 3. — View Citation

Hirano M, Nishino I, Nishigaki Y, Martí R. Thymidine phosphorylase gene mutations cause mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Intern Med. 2006;45(19):1103. Epub 2006 Nov 1. — View Citation

Martí R, López LC, Hirano M. Assessment of thymidine phosphorylase function: measurement of plasma thymidine (and deoxyuridine) and thymidine phosphorylase activity. Methods Mol Biol. 2012;837:121-33. doi: 10.1007/978-1-61779-504-6_8. — View Citation

Valentino ML, Martí R, Tadesse S, López LC, Manes JL, Lyzak J, Hahn A, Carelli V, Hirano M. Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). FEBS Lett. 2007 Jul 24;581(18):3410-4. Epub 2007 Jun 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	neutrophil count (cells/L)	engraftment success	42 days
Secondary	number of patient survival days	is the patient al	100 days
Secondary	chimerism percentage	percent of donor cell chimerism at 100 days	100 days
Secondary	micromole/l dUrd	level of deoxyuridine	100 days
Secondary	micromole Thd	level of thymidine	100 days