Phase II Study of Arginine Butyrate With or Without Epoetin Alfa in Patients With Thalassemia Intermedia - Full Text View

Sponsor:	Boston University
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00006136

Purpose

OBJECTIVES: I. Determine whether arginine butyrate with or without epoetin alfa can stimulate gamma-globin chain production to a degree that decreases anemia and results in hematologic improvement in patients with thalassemia intermedia.

II. Determine whether a proportional increase in gamma-globin synthesis and mRNA and an improvement in nonalfa and alfaglobin chain imbalance by at least 10% over baseline correlate with improved hematologic response in these patients when treated with this regimen.

III. Determine whether a decrease in hemolysis, as assayed by a decrease in LDH, compared to baseline levels correlates with improved hematologic response in these patients when treated with this regimen.

IV. Determine whether any particular genotypes are more responsive than others to this therapy in these patients.

V. Determine whether baseline epoetin alfa levels, gender, and/or baseline reticulocyte counts (or percent circulating nucleated erythroblasts) correlate with improved hematologic response in these patients when treated with this regimen.

Condition	Intervention	Phase
Beta-Thalassemia	Drug: arginine butyrate Drug: epoetin alfa	Phase II

Study Type:	Interventional
Study Design:	Treatment

Resource links provided by NLM:

Genetics Home Reference related topics: beta thalassemia

MedlinePlus related topics: Thalassemia

Drug Information available for: Erythropoietin Arginine butyrate Arginine Epoetin alfa Arginine hydrochloride

U.S. FDA Resources

Further study details as provided by Office of Rare Diseases (ORD):

Estimated Enrollment:	15
Study Start Date:	March 1999

Detailed Description:

PROTOCOL OUTLINE: This is a multicenter study. Patients receive arginine butyrate IV over 6-14 hours on days 1-5 of weeks 1-4 and 7-10. Patients then receive maintenance arginine butyrate IV over 6-14 hours on days 1-4 of weeks 13, 15, 17, 19, 21, 23, and 25.

Patients who have no medical contraindications (e.g., paraspinal extramedullary hematopoiesis, hypertension, or poorly controlled congestive heart failure) may continue therapy. Patients receive arginine butyrate IV over 6-14 hours on days 1-4 of weeks 27, 29, 31, 33, 35, 37, and 39 and epoetin alfa intramuscularly (IM) or subcutaneously (SC) three times weekly on weeks 27-40.

Patients may continue to receive epoetin alfa IM or SC alone three times weekly on weeks 41-52. Patients with severe anemia (hemoglobin less than 7 g/dL) may receive epoetin alfa alone on weeks 1-12 before arginine butyrate induction therapy.

Patients who complete therapy at week 26 are followed every 2 weeks for 2 months. Patients who complete therapy at week 40 are followed monthly for 2 months.

Eligibility

Ages Eligible for Study:	3 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Diagnosis of thalassemia intermedia with hemoglobin no greater than 10 g/dL Two beta thalassemia mutations
Must have undergone prior splenectomy or have no palpable spleen

--Prior/Concurrent Therapy--

At least 3 months since prior red blood cell transfusion

--Patient Characteristics--

Performance status: SWOG 0-2
Hematopoietic: No severe iron overload or ferritin greater than 5,000 ng/mL
Hepatic: Normal hepatic function No active hepatitis
Renal: Normal renal function
Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Must be willing to have vascular access placed No viral disease No contraindication to study compliance

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006136

Locations

United States, California
Children's Hospital of Oakland
Oakland, California, United States, 94609
United States, Connecticut
Yale Comprehensive Cancer Center
New Haven, Connecticut, United States, 06520-8028
United States, Maryland
Clinical Hematology Branch
Bethesda, Maryland, United States, 20892
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
Cancer Research Center
Boston, Massachusetts, United States, 02118
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United Kingdom, England
University College London
London, England, United Kingdom, W1W 7EJ

Sponsors and Collaborators

Boston University

Investigators

Study Chair:

Susan Park Perrine

Boston University

More Information

No publications provided

Study ID Numbers:	199/15337, BUSM-4839
Study First Received:	August 3, 2000
Last Updated:	November 4, 2005
ClinicalTrials.gov Identifier:	NCT00006136 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Office of Rare Diseases (ORD):

genetic diseases and dysmorphic syndromes
hematologic disorders
rare disease
thalassemia intermedia

Additional relevant MeSH terms:

Epoetin Alfa
Antineoplastic Agents
Hematologic Diseases
Hematinics
Hematologic Agents
Anemia
Anemia, Hemolytic
Thalassemia

Pharmacologic Actions
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Beta-Thalassemia
Hemoglobinopathies
Therapeutic Uses
Arginine butyrate

ClinicalTrials.gov processed this record on November 22, 2009