Haploidentical Stem Cell Transplant for Patients With Sickle Cell Disease and Prior Stroke or Abnormal Transcranial Ultrasound - Full Text View

Sponsor:	St. Jude Children's Research Hospital
Information provided by:	St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:	NCT00152113

Purpose

Sickle cell disease is a life-long blood condition that can cause damage to the brain and other organs of the body. Children may develop severe, debilitating clinical states, with stroke or abnormal blood flow to the brain. Treatment generally includes chronic blood transfusions which may cause iron overload, potentially leading to severe and sometimes fatal complications.

Hematopoietic stem cell transplant using cells obtained from a sibling or an unrelated volunteer donor who is a perfect HLA "match" (same tissue type) for the recipient has shown to help, and possibly cure, sickle cell disease. Unfortunately, only about 10-20% of sickle cell patients have a HLA matched sibling donor, and the likelihood of locating an appropriate HLA matched unrelated donor through the various donor registries is limited.

Stem cells from partially HLA matched family members (also called haploidentical transplant) is an option currently being explored for this patient population. This type of transplant has been used and found to be successful in some patients, mostly those with cancers of the blood. However, there can be significant complications with haploidentical transplant, primarily infection, failure of the graft to grow (graft failure), and a disorder called graft-versus-host disease. In addition, few patients with sickle cell disease have undergone this procedure. Therefore, the risks and benefits of haploidentical transplants for patients with sickle cell disorder are not as well established as those using an HLA identical sibling or unrelated donor.

The primary objective of this study is to assess the safety of haploidentical stem cell transplantation for children and adolescents with severe sickle cell disease and stroke or abnormal transcranial Doppler ultrasound requiring chronic transfusion therapy. The treatment plan will be considered safe if there is not excessive toxicity. Toxicity for this protocol is defined as graft failure/graft rejection, severe acute GVHD, or regimen related death within 100 days after the last cellular product administered.

Of note, the protocol was closed to accrual in September 2007 as we had met the stopping rules related to graft integrity (graft failure and graft rejection). Participants currently enrolled continue to be followed per protocol.

Condition	Intervention	Phase
Sickle Cell Disease	Procedure: Hematopoietic Stem Cell Transplantation Device: CliniMACS Drug: See intervention description	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title:	Hematopoietic Stem Cell Transplantation for Patients With Sickle Cell Disease and Prior Stroke or Abnormal Transcranial Doppler Ultrasound Using Reduced-Intensity Conditioning and T-Cell Depleted HSC From Partially Matched Family Donors

Resource links provided by NLM:

Genetics Home Reference related topics: sickle cell disease

MedlinePlus related topics: Anemia Blood Transfusion and Donation Sickle Cell Anemia Ultrasound

U.S. FDA Resources

Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:

To assess the safety of haploidentical stem cell transplantation for children and adolescents with severe sickle cell disease and stroke or abnormal transcranial Doppler ultrasound requiring chronic transfusion therapy. [ Time Frame: September 2007 ] [ Designated as safety issue: Yes ]

Enrollment:	5
Study Start Date:	April 2005
Study Completion Date:	January 2009
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1	Procedure: Hematopoietic Stem Cell Transplantation Allogeneic stem cell transplant Haploidentical stem cell transplant Mismatched family member donor stem cell transplant T cell selection CD34 enrichment Device: CliniMACS Drug: See intervention description Hydroxyurea and azathioprine were administered for a 3 month period prior to the initiation of the transplant procedure in an effort to help prevent rejection of the donor product. Approximately 10 days prior to the transplant procedure, all participants received the same preparative regimen consisting of Busulfan, cyclophosphamide, low-dose thiotepa, and OKT3. MMF was administered for GVHD prophylaxis. Two separate infusions of donor stem cells were administered with fixed doses of CD3 and CD34 cells. These haploidentical stem cells were processed using the investigational CliniMACS device.

Arms

Assigned Interventions

1

Procedure: Hematopoietic Stem Cell Transplantation

Allogeneic stem cell transplant Haploidentical stem cell transplant Mismatched family member donor stem cell transplant T cell selection CD34 enrichment

Device: CliniMACS Drug: See intervention description

Hydroxyurea and azathioprine were administered for a 3 month period prior to the initiation of the transplant procedure in an effort to help prevent rejection of the donor product. Approximately 10 days prior to the transplant procedure, all participants received the same preparative regimen consisting of Busulfan, cyclophosphamide, low-dose thiotepa, and OKT3. MMF was administered for GVHD prophylaxis. Two separate infusions of donor stem cells were administered with fixed doses of CD3 and CD34 cells. These haploidentical stem cells were processed using the investigational CliniMACS device.

Detailed Description:

Secondary objectives for this protocol include the following:

To estimate 1-year overall and event free survival after transplantation. An event is defined as toxicity (graft failure, death, grade III/IV acute GHVD), or a sickle-related event (stroke, acute chest syndrome, pain crisis).
To obtain preliminary information regarding donor engraftment among different cell subsets, including unsorted mononuclear cell, and lymphoid fractions during the first year after transplant.
To observe the rate of acute and chronic GVHD during the first year after transplant.
To assess the proportion of research participants who experience poor graft integrity and therefore require additional donor stem cells or lymphocytes.
To document the effect of stem cell transplant on the central nervous system as defined by radiological imaging and neuropsychological testing.
To investigate immune reconstitution after transplantation

Eligibility

Ages Eligible for Study:	2 Years to 16 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Hemoglobin SS or S-Beta Thalassemia Sickle Cell Disease.
Partially-matched family member with hemoglobin AA (normal) or hemoglobin AS (sickle trait) phenotype.
Stroke (persistent neurologic deficit lasting > 24 hours and present on MRI) or abnormal transcranial Doppler (TCD) ultrasonography requiring chronic transfusion therapy. A TCD is deemed abnormal when the velocity is greater than or equal to 200 cm/sec. Chronic transfusion therapy is defined as "packed red blood cell transfusions administered approximately every 3-5 weeks to decrease the percentage of sickle hemoglobin (Hemoglobin S) to prevent complications of sickle cell disease. This is used most commonly to treat/prevent stroke, acute chest syndrome, and/or pain crises.

Exclusion criteria

Karnofsky or Lansky score < 60%
Acute hepatitis or evidence of moderate or severe portal fibrosis on biopsy. (Biopsy will be obtained if patient on chronic transfusion therapy > 6 months or ferritin > 1000 ng/ml) International normalized ratio (INR) less than 2 times normal. ALT and AST less than 3 times the upper limit of normal.
Severe renal impairment (as evidenced by GFR < 30% predicted normal)
Ejection fraction or shortening fraction below lower limit of normal for age.
Pregnancy
Lactating and pregnant females are excluded
Positive HLA crossmatch with donor.
No sickle cell chronic lung disease > Stage 2

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00152113

Locations

United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105

Sponsors and Collaborators

St. Jude Children's Research Hospital

Investigators

Principal Investigator:

Wing Leung, M.D.

St. Jude Children's Research Hospital

More Information

Additional Information:

St. Jude Children's Research Hospital This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	St. Jude Children's Research Hospital ( Wing Leung, MD / Principal Investigator )
Study ID Numbers:	SCDHAP
Study First Received:	September 7, 2005
Last Updated:	February 3, 2009
ClinicalTrials.gov Identifier:	NCT00152113 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:

Sickle Cell Anemia
Stem Cell Transplantation
Haploidentical stem cell transplant
T cell depletion
CliniMACS device

Additional relevant MeSH terms:

Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies

Anemia
Anemia, Hemolytic
Anemia, Sickle Cell

ClinicalTrials.gov processed this record on February 08, 2010