Stem Cell Transplant for Hemoglobinopathy

NCT ID: NCT00176852

Last Updated: 2020-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-06-30
• Study Completion Date: 2020-01-31

Brief 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.

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.

Conditions

Sickle Cell Disease; Thalassemia; Severe Congenital Neutropenia; Diamond-Blackfan Anemia; Shwachman-Diamond Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RIC Bu/Flu (A) (discontinued)

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.

Group Type: OTHER

Busulfan, Fludarabine, ATG, TLI

Intervention Type: DRUG

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

MA Bu/Cy (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.

Group Type: EXPERIMENTAL

Busulfan, Cyclophosphamide, ATG, GCSF

Intervention Type: DRUG

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

Intervention Type: RADIATION

300 cGY Day -1

Stem cell infusion

Intervention Type: PROCEDURE

Given Day 0

RIC Cy/Flu/TBI (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.

Group Type: EXPERIMENTAL

Campath, Fludarabine, Cyclophosphamide

Intervention Type: DRUG

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

Intervention Type: RADIATION

300 cGY Day -1

Stem cell infusion

Intervention Type: PROCEDURE

Given Day 0

Interventions

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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Total Body Irradiation

300 cGY Day -1

Intervention Type: RADIATION

Stem cell infusion

Given Day 0

Intervention Type: PROCEDURE

Other Intervention Names

Busulfex; Fludara; ATG; Total lymphoid Irradiation; Busulfex; Cytoxan; antithymocyte globulin; granulocyte colony-stimulating factor; Fludara; alemtuzumab; Cytoxan; TBI; bone marrow transplant

Eligibility 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

• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Marrow Donor Program

OTHER

Sponsor Role: collaborator

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angela Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

0206M26241

Identifier Type: OTHER

Identifier Source: secondary_id

MT2002-07

Identifier Type: -

Identifier Source: org_study_id

NCT00005897

Identifier Type: -

Identifier Source: nct_alias