Monoclonal Antibody Conditioning for Allogeneic Stem Cell Transplantation of Patients With Inherited Metabolic Storage Diseases - Full Text View

Sponsors and Collaborators:	Baylor College of Medicine Texas Children's Hospital The Methodist Hospital System
Information provided by:	Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00056979

Purpose

This study treats patients with an inherited disease that prevents the body from making a specific protein or enzyme needed for the body's metabolism. Lack of this enzyme causes accumulation of harmful or toxic substances in the body, which leads to deterioration and failure of organs such as the brain or the heart. This disease can be fatal.

Some patients with inherited metabolic storage disease may benefit from an allogeneic stem cell transplant ('allogeneic' means that the stem cells come from another person). Stem cells are created in the bone marrow. They mature into different types of blood cells that are needed including red blood cells, white blood cells, and platelets. Stem cells, when transplanted, can make a new blood system. Donor stem cells can make the protein or enzyme patients with this disease cells cannot. The donor cells may prevent further accumulation of toxic substances. It is hoped that the donor cells can prevent or stop the disease from progressing.

This research study uses a new pre-treatment combination of two drugs, Anti-CD45 and CAMPATH-1H. Anti-CD45 and CAMPATH-1H are antibodies against certain types of blood cells. CAMPATH-1H is particularly important because it stays active in the body for a long time after infusion, which means it may work longer at preventing GVHD symptoms. In addition to antibodies, patients will receive Fludarabine, which is a chemotherapy drug. Fludarabine kills bone marrow cells and is given to reduce the bone marrow cells so that donor stem cells may 'take.'

Condition	Intervention	Phase
Inherited Metabolic Storage Diseases	Drug: CAMPATH-1H Drug: Anti-CD45 Drug: FK506 Drug: Fludarabine	Phase I Phase II

MedlinePlus related topics: Metabolic Disorders

Drug Information available for: Fludarabine Fludarabine monophosphate Tacrolimus Alemtuzumab Immunoglobulins Globulin, Immune Campath Tacrolimus anhydrous

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Anti-CD45 (YTH-24 & YTH 54) and ANTI-CD52 (CAMPATH-1H) Monoclonal Antibody Conditioning Regimen for Allogeneic Stem Cell Transplantation of Patients With Inherited Metabolic Storage Diseases

Further study details as provided by Baylor College of Medicine:

Estimated Enrollment:	27
Study Start Date:	June 2002

Detailed Description:

Fludarabine will be given as a daily IV (intravenous, by vein) infusion for a total of 5 days. CAMPATH-1H will be given as a daily 4-hour IV (intravenous, by vein) infusion for three days. Anti-CD45 will be given as a daily 6-hour IV infusion over the next 4 days. Then patients will have a one-day rest period before receiving the stem cell transplant. To help prevent the body from rejecting the transplant, patients will also receive the drug FK506, starting two days before the transplant and continuing for three months. If there is no GVHD, the amount of FK506 patients are taking will be reduced by 20% every 2 weeks until this medication is stopped.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

Patients with inherited metabolic storage diseases of all ages are eligible.
Diagnosis of inherited metabolic storage disease confirmed by standard biochemical and genetic studies in consultation with the Department of Genetics at the Baylor College of Medicine
Inherited metabolic storage diseases which may be stabilized or improved by stem cell transplantation include: Hurler, Hunter, Maroteaux-Lamy, Sly, Wolman, Gaucher, Farber, Nieman-Pick, Mannosidosis, Aspartylglucosaminuria, Fucosidosis, Neuronal Ceroid-Lipofuscinosis, Metachromatic Leukodystrophy, Globoid Cell Leukodystrophy, and Adrenoleukodystrophy
Availability of an HLA matched or mismatched (up to one haplotype) donor who is not an obligate carrier for the inherited condition or an unrelated HLA matched stem cell donor. Fully matched is defined as 6/6 match by high resolution DR based DNA typing.
Female patients of childbearing age must have a negative pregnancy test and be willing to use an effective means of birth control.

Exclusion criteria:

Patients with a life expectancy (<6 weeks) limited by diseases other than inherited metabolic storage disease
Patients with advanced inherited metabolic storage disease, which has not been stabilized or improved by hematopoietic stem cell transplantation.
Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram (i.e., shortening fraction <25%)
Patients with severe renal disease (Creatinine >2 x normal for age)
Patients with known allergy to rat serum products
Patients with a Karnofsky or Lansky score <50%.
Patients with a severe infection that on evaluation by the Principal Investigator precludes ablative chemotherapy or successful transplantation
Patients with severe personality disorder or mental illness or neuropsychological evaluation indicating too much damage for the transplant to be of benefit.
Patients with documented HIV positivity.
Patients with grade III-IV liver toxicity not related to metabolic storage disease.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00056979

Locations

United States, Texas
The Methodist Hospital
Houston, Texas, United States
Texas Children's Hospital
Houston, Texas, United States

Sponsors and Collaborators

Baylor College of Medicine

Texas Children's Hospital

The Methodist Hospital System

Investigators

Study Chair:

Malcolm K Brenner, MD

Baylor College of Medicine

More Information

Study ID Numbers:	H11909, MAID
Study First Received:	March 26, 2003
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00056979
Health Authority:	United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:

Metabolic diseases

Study placed in the following topic categories:

Antibodies, Monoclonal
Antibodies
Metabolic Diseases
Alemtuzumab
Tacrolimus

Fludarabine
Fludarabine monophosphate
Metabolic disorder
Immunoglobulins

Additional relevant MeSH terms:

Immunologic Factors
Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009