Ignite Creation Date:
2024-05-05 @ 11:22 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005934
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2000-07-06
Brief Title:
5-Azacytidine and Phenylbutyrate to Treat Severe Thalassemia
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Pilot Study of 5-Azacytidine and Oral Sodium Phenylbutyrate in Severe Thalassemia
Status:
COMPLETED
Status Verified Date:
2003-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the safety and effectiveness of 5-azacytidine and phenylbutyrate for treating thalassemia major Patients with this disease have abnormal production of hemoglobin the oxygen-carrying protein in red blood cells which leads to red blood cell destruction As a result patients require frequent red cell transfusions over many years Because of these transfusions however excess iron is deposited in various body organs-such as the heart liver thyroid gland and in men the testes-impairing their function
Fetal hemoglobin-a type of hemoglobin that is produced during fetal and infant life-can substitute for adult hemoglobin and increase the levels of red cells in the body After infancy however this type of hemoglobin is no longer produced in large quantities 5-azacytidine can increase fetal hemoglobin levels but this drug can damage DNA which in turn can increase the risk of cancer This study will try to lessen the harmful effects of 5-azacytidine by using only one or two doses of it followed by long-term therapy with phenylbutyrate a drug that may be as effective as 5-azacytidine with less harmful side effects
Patients 18 years of age and older with severe thalassemia major may be eligible for this study Before beginning treatment candidates will have a medical history and physical examination blood tests chest X-ray electrocardiogram EKG bone marrow biopsy removal of a small sample of bone marrow from the hip for microscopic examination and whole-body magnetic resonance imaging MRI For the biopsy the area of the hip is anesthetized and a special needle is inserted to draw bone marrow from the hipbone For the MRI scan a strong magnetic field is used to produce images that will identify sites where the body is making red blood cells During this procedure the patient lies on a table in a narrow cylinder containing a magnetic field Earplugs are placed in the ears to muffle the loud thumping sounds the machine makes when the magnetic fields are being switched
An intravenous IV catheter flexible tube inserted into a vein is placed in a large vein of the patients neck chest or arm for infusion of 5-azacytidine at a constant rate over 4 days Patients who do not respond to this first dose of 5-azacytidine will be given the drug again after about 50 days If they do not respond to the second dose alternate treatments will have to be considered Patients who respond to 5-azacytidine will begin taking phenylbutyrate on the 14th day after 5-azacytidine was started They will take about 10 large pills 3 times a day continuing for as long as the treatment is beneficial All patients will be hospitalized for at least 6 days starting with the beginning of 5-azacytidine therapy Those who are well enough may then be discharged and continue treatment as an outpatient
Patients will be monitored with blood tests daily for 2 weeks and then will be seen weekly for about another 5 weeks Bone marrow biopsies will be repeated 6 days after treatment begins and again at 2 weeks and 7 weeks MRI will be repeated 7 weeks after treatment begins After 7 weeks patients will be seen at 3-month intervals Bone marrow biopsies will be done every 6 months for the first 3 years after treatment Patients will have red cell transfusions as needed and chelation therapy to remove excess iron
Fetal hemoglobin-a type of hemoglobin that is produced during fetal and infant life-can substitute for adult hemoglobin and increase the levels of red cells in the body After infancy however this type of hemoglobin is no longer produced in large quantities 5-azacytidine can increase fetal hemoglobin levels but this drug can damage DNA which in turn can increase the risk of cancer This study will try to lessen the harmful effects of 5-azacytidine by using only one or two doses of it followed by long-term therapy with phenylbutyrate a drug that may be as effective as 5-azacytidine with less harmful side effects
Patients 18 years of age and older with severe thalassemia major may be eligible for this study Before beginning treatment candidates will have a medical history and physical examination blood tests chest X-ray electrocardiogram EKG bone marrow biopsy removal of a small sample of bone marrow from the hip for microscopic examination and whole-body magnetic resonance imaging MRI For the biopsy the area of the hip is anesthetized and a special needle is inserted to draw bone marrow from the hipbone For the MRI scan a strong magnetic field is used to produce images that will identify sites where the body is making red blood cells During this procedure the patient lies on a table in a narrow cylinder containing a magnetic field Earplugs are placed in the ears to muffle the loud thumping sounds the machine makes when the magnetic fields are being switched
An intravenous IV catheter flexible tube inserted into a vein is placed in a large vein of the patients neck chest or arm for infusion of 5-azacytidine at a constant rate over 4 days Patients who do not respond to this first dose of 5-azacytidine will be given the drug again after about 50 days If they do not respond to the second dose alternate treatments will have to be considered Patients who respond to 5-azacytidine will begin taking phenylbutyrate on the 14th day after 5-azacytidine was started They will take about 10 large pills 3 times a day continuing for as long as the treatment is beneficial All patients will be hospitalized for at least 6 days starting with the beginning of 5-azacytidine therapy Those who are well enough may then be discharged and continue treatment as an outpatient
Patients will be monitored with blood tests daily for 2 weeks and then will be seen weekly for about another 5 weeks Bone marrow biopsies will be repeated 6 days after treatment begins and again at 2 weeks and 7 weeks MRI will be repeated 7 weeks after treatment begins After 7 weeks patients will be seen at 3-month intervals Bone marrow biopsies will be done every 6 months for the first 3 years after treatment Patients will have red cell transfusions as needed and chelation therapy to remove excess iron
Detailed Description:
Individuals with homozygous beta-thalassemia are either severely anemic or dependent on blood transfusion to sustain life Deficient synthesis of the beta chain leads to imbalanced chain synthesis with an excess of alpha globin This alpha globin precipitates causing ineffective erythropoiesis and shortened red cell survival In patients with homozygous beta-thalassemia enhanced gamma globin synthesis could partially compensate for the deficient synthesis of beta globin rendering chain synthesis more balanced and reducing the relative excess of alpha chains The purpose of this protocol is to test the hypothesis that induction therapy with 5-azacytidine followed by maintenance treatment with oral phenylbutyrate will enhance gamma globin synthesis increase red cell production and partially or substantially correct the anemia in patients with homozygous beta-thalassemia
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 00-DK-0166 | None | None | None |