Stem Cell Transplant for Hemoglobinopathy

NCT00176852 | Completed Phase 2 Results DMC

• 2 other identifiers: MT2002-070206M26241
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

high risk hemoglobinopathy; stem cell transplant; donor lymphocyte infusion; transfusion dependent; stem cell donor; cord blood; marrow; transfusion dependent non-malignant hematologic disorders

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year

Secondary Outcomes (16)

• The Incidence of Chimerism at 100 Days

  100 days

• The Incidence of Chimerism at 6 Months

  6 months

• The Incidence of Chimerism at 1 Year

  1 year

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

  100 days

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

  100 days

Study Arms (3)

RIC Bu/Flu (A) (discontinued)

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.

Drug: Busulfan, Fludarabine, ATG, TLI

MA Bu/Cy (B)

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.

Drug: Busulfan, Cyclophosphamide, ATG, GCSF; Radiation: Total Body Irradiation; Procedure: Stem cell infusion

RIC Cy/Flu/TBI (A2)

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.

Drug: Campath, Fludarabine, Cyclophosphamide; Radiation: Total Body Irradiation; Procedure: Stem cell infusion

Interventions

Busulfan, Fludarabine, ATG, TLI 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

Also known as: Busulfex, Fludara, ATG, Total lymphoid Irradiation

RIC Bu/Flu (A) (discontinued)

Busulfan, Cyclophosphamide, ATG, GCSF 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.

Also known as: Busulfex, Cytoxan, antithymocyte globulin, granulocyte colony-stimulating factor

MA Bu/Cy (B)

Campath, Fludarabine, Cyclophosphamide 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.

Also known as: Fludara, alemtuzumab, Cytoxan

RIC Cy/Flu/TBI (A2)

Total Body Irradiation RADIATION

300 cGY Day -1

Also known as: TBI

MA Bu/Cy (B); RIC Cy/Flu/TBI (A2)

Stem cell infusion PROCEDURE

Given Day 0

Also known as: bone marrow transplant

MA Bu/Cy (B); RIC Cy/Flu/TBI (A2)

Eligibility Criteria

• Age: Up to 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead
• National Marrow Donor Program: collaborator

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Thalassemia; Neutropenia, Severe Congenital, Autosomal Recessive 3; Anemia, Diamond-Blackfan; Shwachman-Diamond Syndrome

Interventions

Busulfan; fludarabine; fludarabine phosphate; Cyclophosphamide; Antilymphocyte Serum; Granulocyte Colony-Stimulating Factor; Alemtuzumab; Whole-Body Irradiation; Bone Marrow Transplantation

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Red-Cell Aplasia, Pure; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Exocrine Pancreatic Insufficiency; Pancreatic Diseases; Digestive System Diseases; Lipid Metabolism, Inborn Errors; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipomatosis

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Radiotherapy; Therapeutics; Investigative Techniques; Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Angela Smith
• Organization: Masonic Cancer Center, University of Minnesota

smith719@umn.edu

612-626-2778

Study Officials

• Angela Smith, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 15, 2005
• Study Start: June 1, 2002
• Primary Completion: March 1, 2014
• Study Completion: January 1, 2020
• Last Updated: February 27, 2020
• Results First Posted: May 9, 2017

Record last verified: 2020-02

Locations

US (1)