MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study (MASS)

• ClinicalTrials.gov Identifier: NCT02427178
• Recruitment Status: Withdrawn
• First Posted: April 27, 2015
• Last Update Posted: August 1, 2022
• Sponsor: Michio Hirano, MD
• Collaborators: Cornell University; National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Michio Hirano, MD, Columbia University

Tracking Information

• First Submitted Date: February 10, 2015
• First Posted Date: April 27, 2015
• Last Update Posted Date: August 1, 2022
• Estimated Study Start Date: March 2015
• Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 22, 2015)

neutrophil count (cells/L) [ Time Frame: 42 days ]

engraftment success

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 22, 2015)

• number of patient survival days [ Time Frame: 100 days ]
  is the patient al
• chimerism percentage [ Time Frame: 100 days ]
  percent of donor cell chimerism at 100 days
• micromole/l dUrd [ Time Frame: 100 days ]
  level of deoxyuridine
• micromole Thd [ Time Frame: 100 days ]
  level of thymidine

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study
• Official Title: MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) AHSCT (Allogeneic Hematopoietic Stem Cell Transplant) Safety Study
• 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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)

Intervention

Biological: Hematopoietic Allogeneic Stem Cells

HLA 10/10 matched allogeneic bone marrow cells will be infused into recipient (patient).

Study Arms

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.

Intervention: Biological: Hematopoietic Allogeneic Stem Cells

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.

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: July 28, 2022): 0
• Original Estimated Enrollment (submitted: April 22, 2015): 12
• Estimated Study Completion Date: June 2023
• Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years to 55 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT02427178
• Other Study ID Numbers: AAAI1718; U54NS078059 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: When applicable, we will submit a manuscript describing the results

• Current Responsible Party: Michio Hirano, MD, Columbia University
• Original Responsible Party: Michio Hirano, Columbia University, Professor of Neurology
• Current Study Sponsor: Michio Hirano, MD
• Original Study Sponsor: Michio Hirano

Collaborators

• Cornell University
• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Michio Hirano, MD; Columbia University

• PRS Account: Columbia University
• Verification Date: July 2022