Overview

This trial is active, not recruiting.

Conditions sickle cell disease, thalassemia, severe congenital neutropenia, diamond-blackfan anemia, shwachman-diamond syndrome
Treatments busulfan, fludarabine, atg, tli, busulfan, cyclophosphamide, atg, gcsf, campath, fludarabine, cyclophosphamide, total body irradiation, stem cell infusion
Phase phase 2/phase 3
Sponsor Masonic Cancer Center, University of Minnesota
Collaborator National Marrow Donor Program
Start date June 2002
End date March 2014
Trial size 30 participants
Trial identifier NCT00176852, 0206M26241, MT2002-07, NCT00005897

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Other)
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.
busulfan, fludarabine, atg, tli Busulfex
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
(Experimental)
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.
busulfan, cyclophosphamide, atg, gcsf Busulfex
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.
total body irradiation TBI
300 cGY Day -1
stem cell infusion bone marrow transplant
Given Day 0
(Experimental)
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.
campath, fludarabine, cyclophosphamide Fludara
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.
total body irradiation TBI
300 cGY Day -1
stem cell infusion bone marrow transplant
Given Day 0

Primary Outcomes

Measure
Grade 3-5 Regimen Related Toxicity
time frame: 1 year

Secondary Outcomes

Measure
Determine the incidence of chimerism at 100 days, 6 months and 1 year.
time frame: 100 days, 6 months and 1 year
Determine the incidence of grade 2-4 and 3-4 acute GVHD at 100 days.
time frame: 100 days
Determine the incidence of chronic GVHD at 6 months and 1 year.
time frame: 6 months and 1 year.
Compare the quality of life (QOL) at 1, 2 and 5 years with the pre-transplant assessment.
time frame: 1, 2 and 5 years
Determine overall and disease free survival at 100 days and 1 year.
time frame: 100 days and 1 year
Determine physical characteristics and biologic effects of mixed populations of donor and host red blood cells
time frame: During study
Determine the concentration of Campath in the serum
time frame: Day 0

Eligibility Criteria

Male or female participants up to 50 years old.

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

Additional Information

Official title Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathy Using a Preparative Regimen to Achieve Stable Mixed Chimerism
Principal investigator Angela Smith, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Masonic Cancer Center, University of Minnesota.