Status: No Longer Recruiting
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").
In this study, we plan to perform AHSCT on at least 3 and at most 12 patients with confirmed MNGIE. We will evaluate mortality, the success of the transplant, biochemical parameters, gastrointestinal function, and nerve functions.
- Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE)
MNGIE is a rare, severe genetic disease. It usually begins to affect patients in their late teenage years. Major symptoms are gastrointestinal (difficulty swallowing, diarrhea, abdominal pain, inability to eat normal size meals), weight loss, droopy eyelids, reduced ability to move eyes, numbness, tingling, and weakness in the hands and feet due to nerve damage. The disease occurs when a person inherits two DNA mutations in the TYMP gene that produces the protein thymidine phosphorylase (TP). Low levels of TP activity, or no TP activity, cause toxic accumulations of thymidine (Thd) and deoxyuridine (dUrd). These toxic accumulations prevent the mitochondria, the energy producing parts of the cell, from producing enough energy.
The therapeutic efficacy of AHSCT is supported by preliminary results in 10 surviving, successfully transplanted MNGIE patients who have shown restoration of circulating TP activity, marked reductions of the toxic metabolites, Thd and dUrd, and time-dependent clinical improvements.
The Single Primary Aim is to confirm that primary graft failure by day 42 post-transplant and mortality from initiation of conditioning regimen through day 100 post-transplant are acceptable in a one-arm safety study of the consensus AHSCT protocol for MNGIE.
There are 5 Secondary Aims:
- To confirm that additional safety outcomes do not reach an unacceptable level through day 100 post-transplant.
- To evaluate the change in key biological and clinical outcome measures from baseline through day 100 post-transplant.
- To collect preliminary safety data through two years post-transplant.
- To evaluate the change from baseline through two years post-transplant in key biological and clinical outcome measures.
- To assess, and revise as appropriate, the recruitment, retention, patient management, and data management procedures for the planned biological allocation Phase II trial comparing AHSCT to standard of care for MNGIE patients.