Stem Cell Transplant for Hemoglobinopathy

Masonic Cancer Center, University of Minnesota22 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Sickle Cell Disease Thalassemia

Interventions

Busulfan, Fludarabine, ATG, TLIDRUG

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

Busulfan, Cyclophosphamide, ATG, GCSFDRUG

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.

Campath, Fludarabine, CyclophosphamideDRUG

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 IrradiationRADIATION

300 cGY Day -1

Stem cell infusionPROCEDURE

Given Day 0

Eligibility

Sex: ALLMax age: 50 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Number of Patients Who Experienced Grade 3-5 Treatment Related Toxicity

In general, grade 3 equates to moderate, grade 4 to severe and grade 5 to death.

Time frame: 1 year

Secondary Outcomes

The Incidence of Chimerism at 100 Days

The number of patients whose blood and/or bone marrow contains \> 10% donor cells.

Time frame: 100 days

The Incidence of Chimerism at 6 Months

The number of patients whose blood and/or bone marrow contains \> 10% donor cells.

Time frame: 6 months

The Incidence of Chimerism at 1 Year

The number of patients whose blood and/or bone marrow contains \> 10% donor cells.

Time frame: 1 year

The Incidence of Grade 2-4 Acute Graft Versus Host Disease (Acute GVHD)

The number of patients who experienced grades 2-4 Acute GVHD. Acute GVHD is when the donated bone marrow or peripheral blood stem cells view the recipient's body as foreign, and the donated cells/bone marrow attack the body. Grades 2-4 equate to mild to severe disease. Symptoms typically appear within weeks after transplant.

Time frame: 100 days

The Incidence of Grade 3-4 Acute Graft Versus Host Disease (Acute GVHD)

The number of patients who experienced grades 3-4 Acute GVHD. Acute GVHD is when the donated bone marrow or peripheral blood stem cells view the recipient's body as foreign, and the donated cells/bone marrow attack the body. IGrades 3-4 equate to moderate to severe disease. Symptoms typically appear within weeks after transplant.

Time frame: 100 days

The Incidence of Chronic Graft Versus Host Disease (Chronic GVHD)

The number of patients who experienced Chronic GVHD. Chronic GVHD is when the donated bone marrow or peripheral blood stem cells view the recipient's body as foreign, and the donated cells/bone marrow attack the body. Chronic GVHD can appear at any time after allogeneic transplant or several years after transplant.

Time frame: 6 months

The Incidence of Chronic Graft Versus Host Disease (Chronic GVHD)

Time frame: 1 year

Change in the Patient's Quality of Life as Compared to the Pre-Transplant Assessment

The measure for quality of life used in this study is the Karnofsky Performance Score. The Karnofsky Performance Score runs from 100 to 0, where 100 is "perfect" health and 0 is death.

Time frame: pre-transplant

Change in the Patient's Quality of Life as Compared to the Pre-Transplant Assessment

The measure for quality of life used in this study is the Karnofsky Performance Score. The Karnofsky Performance Score runs from 100 to 0, where 100 is "perfect" health and 0 is death.

Time frame: 1 year

Change in the Patient's Quality of Life as Compared to the Pre-Transplant Assessment

The measure for quality of life used in this study is the Karnofsky Performance Score. The Karnofsky Performance Score runs from 100 to 0, where 100 is "perfect" health and 0 is death.

Time frame: 2 years

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

Overall Survival

Number of patients alive 100 days after transplant.

Time frame: 100 days

Overall Survival

Number of patients alive 1 year after transplant.

Time frame: 1 year

Disease Free Survival

Number of patients alive without disease 100 days after transplant.

Time frame: 100 days

Disease Free Survival

Number of patients alive without disease 1 year after transplant.

Time frame: 1 year

Stem Cell Transplant for Hemoglobinopathy

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes