Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00011505
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
2001-02-22
Brief Title:
Mobilization of Stem Cells With G-CSF for Collection From Patients With Diamond-Blackfan Anemia
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Investigation of G-CSF-Induced Stem Cell Mobilization Potential in Patients With Diamond-Blackfan Anemia
Status:
COMPLETED
Status Verified Date:
2006-04
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 provide information needed to develop more effective treatments for patients with Diamond-Blackfan anemia DBA Current treatments include steroids such as prednisone and blood transfusions These treatments have potential long-term risk and side effects including osteoporosis and impaired growth from steroids or iron overload from transfusions In addition as patients reach adulthood they can develop acute leukemia or bone marrow failure The only cure for DBA is bone marrow transplant a procedure that itself carries serious risks and is an option for only about 25 percent of patients
DBA is caused by a mutation error in a gene that codes for producing red blood cells from stem cells blood-forming cells produced by the bone marrow In 5 to 10 years gene transfer therapy may prove to be an effective treatment for DBA Before this treatment can be considered however more information is needed about DBA patients and how their stem cells function This study will examine 1 whether stem cells of patients with DBA respond to G-CSF the same way those of healthy people do G-CSF is a drug that causes stem cells to move from the bone marrow to the blood stream where they can be collected more easily and in larger numbers by a procedure called leukapheresis described below If G-CSF does not work well in DBA patients other collection strategies will have to be explored and 2 whether the genetic error in DBA can be corrected by gene transfer into patients stem cells
Patients with Diamond-Blackfan anemia 4 years of age and older who weigh at least 27 pounds and who are dependent on red blood cell transfusions may be eligible for this study Candidates will have a medical history taken and a physical examination and will be seen by the Clinical Centers Department of Medicine Transfusion for leukapheresis evaluation They will have a bone marrow aspiration and biopsy to confirm the diagnosis of DBA For these tests the hip area is anesthetized and a needle is used to draw bone marrow from the hipbone If needed the procedure will be done under sedation
Patients will be given G-CSF by injection under the skin for up to 6 days Blood and stem cell counts will be measured from a teaspoon of blood drawn each morning On the morning of the fifth dose the patient will undergo leukapheresis for collection of stem cells For this procedure a large catheter with a diameter no larger than that of a straw is placed in an arm vein to allow blood to flow into a cell separator machine Most children and some adults do not have veins large and strong enough for this tubing so a large intravenous line called a central line is placed into a large vein in the neck or groin This is done under sedation and with a local anesthetic While the patient lies on a bed or recliner whole blood is collected through a catheter in one arm or the central line the stem cells are separated out by spinning then the red cells platelets and plasma are returned through a second catheter in the other arm or a second opening in the central line The procedure takes about 3 to 5 hours during which the patient can watch television or videos and have family members at the bedside for company When the procedure is completed the patients participation in the protocol ends
Some of the stem cells collected by leukapheresis will be used for research and some will be frozen and stored for possible future transplantation into the patient if required
DBA is caused by a mutation error in a gene that codes for producing red blood cells from stem cells blood-forming cells produced by the bone marrow In 5 to 10 years gene transfer therapy may prove to be an effective treatment for DBA Before this treatment can be considered however more information is needed about DBA patients and how their stem cells function This study will examine 1 whether stem cells of patients with DBA respond to G-CSF the same way those of healthy people do G-CSF is a drug that causes stem cells to move from the bone marrow to the blood stream where they can be collected more easily and in larger numbers by a procedure called leukapheresis described below If G-CSF does not work well in DBA patients other collection strategies will have to be explored and 2 whether the genetic error in DBA can be corrected by gene transfer into patients stem cells
Patients with Diamond-Blackfan anemia 4 years of age and older who weigh at least 27 pounds and who are dependent on red blood cell transfusions may be eligible for this study Candidates will have a medical history taken and a physical examination and will be seen by the Clinical Centers Department of Medicine Transfusion for leukapheresis evaluation They will have a bone marrow aspiration and biopsy to confirm the diagnosis of DBA For these tests the hip area is anesthetized and a needle is used to draw bone marrow from the hipbone If needed the procedure will be done under sedation
Patients will be given G-CSF by injection under the skin for up to 6 days Blood and stem cell counts will be measured from a teaspoon of blood drawn each morning On the morning of the fifth dose the patient will undergo leukapheresis for collection of stem cells For this procedure a large catheter with a diameter no larger than that of a straw is placed in an arm vein to allow blood to flow into a cell separator machine Most children and some adults do not have veins large and strong enough for this tubing so a large intravenous line called a central line is placed into a large vein in the neck or groin This is done under sedation and with a local anesthetic While the patient lies on a bed or recliner whole blood is collected through a catheter in one arm or the central line the stem cells are separated out by spinning then the red cells platelets and plasma are returned through a second catheter in the other arm or a second opening in the central line The procedure takes about 3 to 5 hours during which the patient can watch television or videos and have family members at the bedside for company When the procedure is completed the patients participation in the protocol ends
Some of the stem cells collected by leukapheresis will be used for research and some will be frozen and stored for possible future transplantation into the patient if required
Detailed Description:
Diamond-Blackfan anemia DBA is a congenital hypoproliferative anemia that generally presents in infancy The mainstays of treatment prednisone and transfusion therapy have long-term toxicity in many patients and bone marrow transplantation with an HLA-matched donor is an option for only a minority of patients Most importantly patients with DBA have an increased risk of progression of myelodysplastic syndrome leukemia and aplastic anemia compared to the general population
The characterization of potentially mutated genes in DBA is an area of active research and at least one mutation present in about one-fourth of DBA patients may cause disease due to decreased production of a ribosomal protein This finding raises the possibility that the disease at least in some patients may be correctable by genetic therapy by which a normal copy of the mutated gene can be introduced into the stem cells which give rise to red cells
It is therefore of interest to identify any particular characteristics of DBA patients which might delay or hinder the application of gene therapy to their disease This pilot study of 15 patients is designed to evaluate 1 the CD34 cell mobilization response to administration of standard doses of granulocyte-colony stimulating factor G-CSF 2 the potential for stem cells from DBA patients to be collected by large volume leukapheresis of subjects who have been given G-CSF and 3 the ability of these G-CSF mobilized cells to be transduced with vectors being developed for gene therapy applications Outcome parameters to be monitored are the mobilization response to G-CSF the safety profile and tolerance of G-CSF and leukapheresis and the efficiency of transduction of DBA stem cells with standard gene therapy vectors Effectiveness will be gauged by historical comparison of these parameters to normal healthy age-matched volunteer
It is important to point out that there is no therapeutic intent to the majority of this protocol or direct benefit for enrolled patients We do plan however to cryopreserve the remainder of the mobilized cells collected by apheresis for possible autologous transplantation in the event of the patients progression to leukemia of bone marrow failure in the future
The characterization of potentially mutated genes in DBA is an area of active research and at least one mutation present in about one-fourth of DBA patients may cause disease due to decreased production of a ribosomal protein This finding raises the possibility that the disease at least in some patients may be correctable by genetic therapy by which a normal copy of the mutated gene can be introduced into the stem cells which give rise to red cells
It is therefore of interest to identify any particular characteristics of DBA patients which might delay or hinder the application of gene therapy to their disease This pilot study of 15 patients is designed to evaluate 1 the CD34 cell mobilization response to administration of standard doses of granulocyte-colony stimulating factor G-CSF 2 the potential for stem cells from DBA patients to be collected by large volume leukapheresis of subjects who have been given G-CSF and 3 the ability of these G-CSF mobilized cells to be transduced with vectors being developed for gene therapy applications Outcome parameters to be monitored are the mobilization response to G-CSF the safety profile and tolerance of G-CSF and leukapheresis and the efficiency of transduction of DBA stem cells with standard gene therapy vectors Effectiveness will be gauged by historical comparison of these parameters to normal healthy age-matched volunteer
It is important to point out that there is no therapeutic intent to the majority of this protocol or direct benefit for enrolled patients We do plan however to cryopreserve the remainder of the mobilized cells collected by apheresis for possible autologous transplantation in the event of the patients progression to leukemia of bone marrow failure in the future
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 |
|---|---|---|---|
| 01-H-0097 | None | None | None |