Trial record 1 of 1 for:    NCT00176852
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Stem Cell Transplant for Hemoglobinopathy

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Collaborator:
National Marrow Donor Program
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00176852
First received: September 12, 2005
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

This study tests the clinical outcomes of one of two preparative regimens (determined by available donor source) in patients with non-malignant hemoglobinopathies. The researchers hypothesize that these regimens will have a positive effect on post transplant engraftment and the incidence of graft-versus-host-disease.

Regimen A2 has replaced Regimen A in this study. Two patients were treated on Regimen A but did not have evidence of initial engraftment thus triggering the stopping rule for that arm of this study.


Condition Intervention Phase
Sickle Cell Disease
Thalassemia
Severe Congenital Neutropenia
Diamond-Blackfan Anemia
Shwachman-Diamond Syndrome
Drug: Busulfan, Fludarabine, ATG, TLI
Drug: Busulfan, Cyclophosphamide, ATG, GCSF
Drug: Campath, Fludarabine, Cyclophosphamide
Radiation: Total Body Irradiation
Procedure: Stem cell infusion
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathy Using a Preparative Regimen to Achieve Stable Mixed Chimerism

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Grade 3-5 Regimen Related Toxicity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine the incidence of chimerism at 100 days, 6 months and 1 year. [ Time Frame: 100 days, 6 months and 1 year ] [ Designated as safety issue: No ]
  • Determine the incidence of grade 2-4 and 3-4 acute GVHD at 100 days. [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Determine the incidence of chronic GVHD at 6 months and 1 year. [ Time Frame: 6 months and 1 year. ] [ Designated as safety issue: Yes ]
  • Compare the quality of life (QOL) at 1, 2 and 5 years with the pre-transplant assessment. [ Time Frame: 1, 2 and 5 years ] [ Designated as safety issue: No ]
  • Determine overall and disease free survival at 100 days and 1 year. [ Time Frame: 100 days and 1 year ] [ Designated as safety issue: No ]
  • Determine physical characteristics and biologic effects of mixed populations of donor and host red blood cells [ Time Frame: During study ] [ Designated as safety issue: No ]
  • Determine the concentration of Campath in the serum [ Time Frame: Day 0 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: December 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Full Conditioning (discontinued / A)
Full Preparative Regimen for subjects with matched donors using Busulfan on Day -8 and -7, Fludarabine on Day -6 through -2, antithymocyte globulin (ATG) on Day -2 through -1, total lymphoid radiation (TLI) on Day -1, stem cell infusion on Day 0.
Drug: Busulfan, Fludarabine, ATG, TLI
Busulfan 0.8 mg/kg/dose intravenous (IV) Days -8 and -7 Fludarabine 35 mg/m2 IV Days -6 through -2 Antithymocyte globulin (ATG) 30 mg/kg IV Days -2 and -1 Total lymphoid radiation 300 cGy
Other Names:
  • Busulfex
  • Fludara
  • ATG
  • Total lymphoid Irradiation
Experimental: Busulfan Conditioning (B)
Myeloablative Preparative Regimen for subjects with HLA identical sibling donors consists of Busulfan on day -9 through -6, Cyclophosphamide on day -5 through -2, ATG on day -3 through -1, stem cell infusion on Day 0 and Granulocyte Colony Stimulating Factor on day -3 until ANC >2500 x 2 days.
Drug: Busulfan, Cyclophosphamide, ATG, GCSF
Busulfan 0.8 mg/kg/dose intravenous (IV) Days -9 through -6 Cyclophosphamide 50 mg/kg IV Days -5 through -2 ATG 30 mg/kg IV Day -1 GCSF 5 mcg/kg/day IV until ANC >2500 x 2 days.
Other Names:
  • Busulfex
  • Cytoxan
  • antithymocyte globulin
  • granulocyte colony-stimulating factor
Radiation: Total Body Irradiation
300 cGY Day -1
Other Name: TBI
Procedure: Stem cell infusion
Given Day 0
Other Name: bone marrow transplant
Experimental: Campath and TBI conditioning (A2)
Patients with sickle cell disease or thalassemia who do not have an HLA-identical sibling donor or who has pre-existing organ dysfunction making myeloablative condition ineligible will receive Campath on day -10 through -6, Cyclophosphamide on day -7, Fludarabine on day -6 through -2, total body irradiation (TBI) on day -1, stem cell infusion on Day 0.
Drug: Campath, Fludarabine, Cyclophosphamide
Receives Campath-1H 0.2 mg/kg Days -10 through -6, Fludarabine 35 mg/m2 intravenous (IV) Days -6 through -2, total body irradiation (TBI) 300 cGy Day -1.
Other Names:
  • Fludara
  • alemtuzumab
  • Cytoxan
Radiation: Total Body Irradiation
300 cGY Day -1
Other Name: TBI
Procedure: Stem cell infusion
Given Day 0
Other Name: bone marrow transplant

Detailed Description:

Prior to transplantation, subjects will receive either:

Cyclophosphamide, Fludarabine, Campath, Total body irradiation (TBI)

Or

Busulfan, Cyclophosphamide, antithymocyte globulin (ATG), granulocyte colony-stimulating factor (GSCF)

These drugs (and the radiation) are being given to help the new stem cells take and grow. On the day of transplantation, subjects will receive stem cells transfused via intravenous (IV) catheter.

After stem cell transplantation, subjects will be given cyclosporine-A and mycophenolate (MMF)/or Methylprednisone/or Methotrexate to reduce the risk of graft-versus-host disease, the complication that occurs when the donor's stem cells react against the patient.

  Eligibility

Ages Eligible for Study:   up to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with Sickle Cell Disease/Thalassemia (SCD/THAL) 0-50 years of age with an acceptable stem cell donor and disease characteristic defined by the following:

    • Stroke, central nervous system (CNS) hemorrhage or a neurologic event lasting longer than 24 hours, or abnormal cerebral magnetic resonance imaging (MRI) or cerebral arteriogram or MRI angiographic study and impaired neuropsychological testing
    • Acute chest syndrome with a history of recurrent hospitalizations or exchange transfusions
    • Recurrent vaso-occlusive pain 3 or more episodes per year for 3 years or more years or recurrent priapism,
    • Impaired neuropsychological function and abnormal cerebral MRI scan
    • Stage I or II sickle lung disease,
    • Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate [GFR] 30-50% of the predicted normal value)
    • Bilateral proliferative retinopathy and major visual impairment in at least one eye
    • Osteonecrosis of multiple joints with documented destructive changes
    • Requirement for chronic transfusions but with red blood cell (RBC) alloimmunization >2 antibodies during long term transfusion therapy
  • Patients with transfusion dependent alpha- or beta-thalassemia 0-35 years of age with an acceptable stem cell donor as defined in the criteria in section above.
  • Patients with other non-malignant hematologic disorders that are transfusion-dependent or involve other potentially life-threatening cytopenias (including but not limited to Severe Congenital Neutropenia, Diamond-Blackfan Anemia and Shwachman-Diamond Syndrome) who are 0-35 years of age with an acceptable stem cell donor
  • Second Transplants

    • Patients with sickle cell disease or thalassemia who have failed to engraft or have autologous recovery after a myeloablative SCT regimen or non-myeloablative regimen are eligible for this protocol.
    • Regimen A2 will be utilized for patients with sickle cell disease or thalassemia who do not have an HLA-identical sibling donor or for any patient who has pre-existing organ dysfunction making them ineligible for a myeloablative preparative regimen.
    • Regimen B will be utilized for patients with sickle cell disease or thalassemia who have an HLA-identical sibling donor.
    • Patients must meet above criteria.
    • If the patient has received prior radiation therapy, eligibility to receive additional radiation therapy must be determined by Dr. Dusenbery
    • If first transplant was a non-myeloablative regimen, the second transplant can occur at any time
    • If the first transplant was a myeloablative regimen, then the second transplant must be > 6 months from the first transplant

Exclusion Criteria:

  • Patients with one or more of the following:
  • Karnofsky or Lansky performance score <70
  • Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
  • Stage III-IV lung disease
  • GFR<30% predicted
  • Pregnant or lactating females
  • Active serious infection whereby patient has been on intravenous antibiotics for one week prior to study entry. Any patient with AIDS or ARC or HIV seropositivity
  • Psychologically incapable of undergoing bone marrow transplant (BMT) with associated strict isolation or documented history of medical non-compliance
  • Patients not able to receive total lymphocytic irradiation (TLI) due to prior radiation therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00176852

Contacts
Contact: Timothy Krepski, RN 612-273-2800 tkrepsk1@fairview.org

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Tim Krepski, RN    612-273-2800    tkrepsk1@fairiview.org   
Principal Investigator: Angela Smith, MD         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
National Marrow Donor Program
Investigators
Principal Investigator: Angela Smith, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00176852     History of Changes
Obsolete Identifiers: NCT00005897
Other Study ID Numbers: MT2002-07, 0206M26241
Study First Received: September 12, 2005
Last Updated: May 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:
high risk hemoglobinopathy
stem cell transplant
donor lymphocyte infusion
transfusion dependent
stem cell donor
cord blood
marrow
transfusion dependent non-malignant hematologic disorders

Additional relevant MeSH terms:
Anemia
Anemia, Sickle Cell
Hemoglobinopathies
Neutropenia
Thalassemia
Bone Marrow Diseases
Lipomatosis
Exocrine Pancreatic Insufficiency
Anemia, Diamond-Blackfan
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Genetic Diseases, Inborn
Agranulocytosis
Leukopenia
Leukocyte Disorders
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Pancreatic Diseases
Digestive System Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Red-Cell Aplasia, Pure
Antilymphocyte Serum
Busulfan
Cyclophosphamide
Fludarabine phosphate
Lenograstim
Fludarabine

ClinicalTrials.gov processed this record on August 01, 2014