Bone Marrow Transplantation, Hemoglobinopathies, SCALLOP

This study has been terminated.
(Terminated due to no new subject enrollment during the last 3 year period.)
Sponsor:
Collaborators:
Texas Children's Hospital
The Methodist Hospital System
Information provided by (Responsible Party):
Kathryn Leung, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00578344
First received: December 19, 2007
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

Patients are being asked to participate in this study because they have severe sickle cell anemia (SCD) with or without the beta thalassemia trait. Sickle cell anemia is an illness where the red blood cells change shape and can clog up blood vessels. This keeps the body from getting the oxygen it needs. Thalassemia is when the body does not make enough hemoglobin, something that helps the oxygen get to the places it needs to go in the body. The patient may or may not need to get regular blood transfusions (getting more blood) to improve their quality of life (feel better) and prevent organ damage (problems with the brain, heart, lung, kidney, and gonad, for example.). The transfusions can also cause problems, including iron overload (too much iron in the blood), which can be fatal (patients can die) without regular deferoxamine shots. Even with the best usual treatments, people with thalassemia or SCD die sooner. There is no proven cure.

We would like to treat patients using bone marrow transplantation, a treatment that has been used for people with SCD. The transplant uses healthy "matched" bone marrow. This comes from a brother or sister who does not have sickle cell disease or severe thalassemia. If the treatment works, the sickle cell disease or thalassemia may be cured. This treatment has been used to treat patients with sickle cell disease or thalassemia. It has worked in most cases. We hope, but cannot promise, that the transplanted marrow will make healthy cells, and patients will not have sickle cell disease or severe thalassemia anymore.

We do not know what effect this treatment will have on the damage that has already been done by the disease. Finding that out is the main reason for this study. Currently, very little has been reported about organ function after bone marrow transplants in patients with sickle cell anemia.


Condition Intervention
Sickle Cell Disease
Hemoglobin SC
Drug: Busulfan
Biological: Campath 1H
Drug: Cyclophosphamide and MESNA

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Bone Marrow Transplantation From HLA Identical Related Donors for Patients With Hemoglobinopathies: Hemoglobin SS, Hemoglobin SC, or Hemoglobin SB0/+ Thalassemia

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Evaluate recovery of organ function in patients with sickle cell disease (SCD) or sickle hemoglobin variants after undergoing allogeneic SCT/BMT from HLA genotype identical donors and if they can be improved or reversed. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Evaluate the use of PET scan examination in assessing metabolic function of organs in patients with SCD, hemoglobin SC, or hemoglobin Sb0/+ after undergoing allogeneic SCT/BMT from HLA genotype identical donors. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Evaluate response to immunization after BMT in patients with SCD, hemoglobin SC, or hemoglobin Sb0/+. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: July 2005
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allogeneic BMT/SCT Transplant

Busulfan, Campath 1H, Cyclophosphamide and MESNA:

Bone marrow infusion with pre-meds as per SOPs to take place on Day 0.

Bone marrow dose: To ensure the probability for bone marrow engraftment, 4 x 10^8 nucleated cells/kg patient weight will be the target at donor bone marrow harvest.

Drug: Busulfan
Starting Day -9 / Busulfan 4.0 mg/kg/day IV divided into four doses daily for four days; total dose = 16 mg/kg.
Other Name: Myleran
Biological: Campath 1H
Day -5 through Day -2; Campath-1H dosed as per institutional guidelines.
Drug: Cyclophosphamide and MESNA
Day -5 through Day -2; Cyclophosphamide 50 mg/kg + MESNA.
Other Name: CTX

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with a related HLA genotype identical donor and hemoglobin SS, hemoglobin SC, or hemoglobin Sb0/+ and at least one of the following conditions:

    1. Previous central nervous system vaso-occlusive episode with or without residual neurologic findings, or has an abnormal transcranial doppler exam without neurologic findings, or abnormal MRI/MRA of the brain with or without neurologic findings;
    2. Frequent painful vaso-occlusive episodes which significantly interfere with normal life activities and which necessitate chronic transfusion therapy;
    3. Recurrent SCD chest syndrome events, which necessitate chronic transfusion therapy;
    4. Severe anemia which prevents acceptable quality of life and necessitates chronic transfusion therapy;
    5. Any of the above symptoms in which the patient is not undergoing chronic transfusion therapy;
    6. The patient is undergoing chronic transfusion therapy for symptoms other than those listed and which significantly interferes with normal life activities;
    7. Failed hydroxyurea therapy;
    8. Indication of pulmonary hypertension on 2 separate echocardiogram examinations;
    9. Patients who plan to return to resource poor areas/countries.
  2. Between the ages of birth and 40 years.
  3. Women of childbearing potential must have a negative pregnancy test.

EXCLUSION CRITERIA:

  1. Patient with biopsy proven chronic active hepatitis or fibrosis with portal bridging.
  2. Patient with SCD chronic lung disease > stage 3 (see Appendix 1).
  3. Patient with severe renal dysfunction defined as creatinine clearance < 40 mL/min/1.73 M^2.
  4. Patient with severe cardiac dysfunction defined as echocardiogram shortening fraction < 25% or NYHA class III or IV.
  5. Patient with HIV infection.
  6. Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate bone marrow transplantation.
  7. Patient or patient's guardian(s) unable to understand the nature and risks inherent in the BMT process.
  8. Pregnant/lactating women and those unwilling to use acceptable contraception will be excluded.
  9. Patient or patient's guardian who have not signed an informed consent.

NOTE: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigator's discretion after approval by the CAGT Protocol Review Committee and the FDA reviewer.

  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: NCT00578344

Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Methodist Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Investigators
Principal Investigator: Kathryn Suet Wa Leung, MD Baylor College of Medicine/Texas Children's Hospital
  More Information

No publications provided

Responsible Party: Kathryn Leung, Assistant Professor, Center for Cell and Gene Therapy, Baylor College of Medicine, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00578344     History of Changes
Other Study ID Numbers: H-16447-SCALLOP, SCALLOP
Study First Received: December 19, 2007
Last Updated: April 22, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
Sickle Cell Disease
SCD
Hemoglobin SS
Hemoglobin SC
Hemoglobin Sb0/+
HLA genotype
Severe anemia
Transfusion therapy

Additional relevant MeSH terms:
Anemia, Sickle Cell
Hemoglobin SC Disease
Hemoglobinopathies
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Genetic Diseases, Inborn
Mesna
Busulfan
Cyclophosphamide
Alemtuzumab
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014