MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study (MASS)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
• Intervention / Treatment: Biological: Hematopoietic Allogeneic Stem Cells

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 Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 55 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Open label; 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; HLA 10/10 matched allogeneic bone marrow cells will be infused into recipient (patient).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Michio Hirano, MD
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Cornell University

Publications and helpful links

General Publications

• Halter J, Schupbach W, Casali C, Elhasid R, Fay K, Hammans S, Illa I, Kappeler L, Krahenbuhl 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.
• Marti R, Lopez 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.
• Hirano M, Nishino I, Nishigaki Y, Marti R. Thymidine phosphorylase gene mutations cause mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Intern Med. 2006;45(19):1103. doi: 10.2169/internalmedicine.45.6064. Epub 2006 Nov 1. No abstract available.
• Valentino ML, Marti R, Tadesse S, Lopez 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. doi: 10.1016/j.febslet.2007.06.042. Epub 2007 Jun 27.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2015
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): June 1, 2023

Study Registration Dates

• First Submitted: February 10, 2015
• First Submitted That Met QC Criteria: April 22, 2015
• First Posted (ESTIMATE): April 27, 2015

Study Record Updates

• Last Update Posted (ACTUAL): August 1, 2022
• Last Update Submitted That Met QC Criteria: July 28, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Stem Cell transplant; Allogeneic Hematopoietic Stem Cell Transplantation; MNGIE
• Other Study ID Numbers: AAAI1718; U54NS078059 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: When applicable, we will submit a manuscript describing the results