Clinical trial NCT02427178: MNGIE Allogeneic Hematopoietic Stem Cell Transplant Safety Study
Official title: MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) AHSCT (Allogeneic Hematopoietic Stem Cell Transplant) Safety Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE)
Keywords: Allogeneic Hematopoietic Stem Cell Transplantation
MNGIE
Stem Cell transplant
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Cornell University
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2015-04-27
Enrollment: 0
Sex: ALL
Minimum age (years): 5
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: neutrophil count (cells/L)
timeFrame: 42 days
Secondary outcomes:
measure: number of patient survival days
timeFrame: 100 days
measure: chimerism percentage
timeFrame: 100 days
measure: micromole/l dUrd
timeFrame: 100 days
measure: micromole Thd
timeFrame: 100 days
Other outcomes:
Locations:
Study officials:
affiliation: Columbia University
name: Michio Hirano, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.