Bone Marrow Transplantation, Hemoglobinopathies, SCALLOP

NCT00578344 | Terminated Results DMC

• 2 other identifiers: H-16447-SCALLOPSCALLOP
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Sickle Cell Disease; Hemoglobin SC

Keywords

Sickle Cell Disease; SCD; Hemoglobin SS; Hemoglobin SC; Hemoglobin Sb0/+; HLA genotype; Severe anemia; Transfusion therapy

Outcome Measures

Primary Outcomes (3)

• Number of Participants Evaluated for Evidence of Recovery of Organ Function Measured Via MRI or PET Scan.

  Assess Number of participants that recovered organ function diagnosed with sickle cell disease (SCD) or sickle hemoglobin variants after undergoing allogeneic SCT/BMT from HLA genotype identical donors.

  One year

• Number of Participants With Pre and Post Transplant PET Scan to Assess Organ Recovery Based on Rate of Acquisition.

  Number of participants that did or did not have pre- and post- PET scans.

  One year

• Number of Participants With Immune Response to Immunization After BMT in Participants With SCD, Hemoglobin SC, or Hemoglobin Sb0/+.

  Vaccine response will be measured via a humoral immunity panel evaluating streptococcus pneumonia IgG antibodies (microgram/mL). Panels are obtained pre and 1+ month post vaccination. Standard recommendations define a normal responder as having \>4 fold increase in antibody level in 50-70% of the serotypes found in the vaccine.

  up to 12 months

Study Arms (1)

Allogeneic BMT/SCT Transplant

EXPERIMENTAL

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; Biological: Campath 1H; Drug: Cyclophosphamide and MESNA

Interventions

Busulfan DRUG

Starting Day -9 / Busulfan 4.0 mg/kg/day IV divided into four doses daily for four days; total dose = 16 mg/kg.

Also known as: Myleran

Allogeneic BMT/SCT Transplant

Campath 1H BIOLOGICAL

Day -5 through Day -2; Campath-1H dosed as per institutional guidelines.

Allogeneic BMT/SCT Transplant

Cyclophosphamide and MESNA DRUG

Day -5 through Day -2; Cyclophosphamide 50 mg/kg + MESNA.

Also known as: CTX

Allogeneic BMT/SCT Transplant

Eligibility Criteria

• Age: Up to 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with a related HLA genotype identical donor and hemoglobin SS, hemoglobin SC, or hemoglobin Sb0/+ and at least one of the following conditions:
• 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;
• Frequent painful vaso-occlusive episodes which significantly interfere with normal life activities and which necessitate chronic transfusion therapy;
• Recurrent SCD chest syndrome events, which necessitate chronic transfusion therapy;
• Severe anemia which prevents acceptable quality of life and necessitates chronic transfusion therapy;
• Any of the above symptoms in which the patient is not undergoing chronic transfusion therapy;
• The patient is undergoing chronic transfusion therapy for symptoms other than those listed and which significantly interferes with normal life activities;
• Failed hydroxyurea therapy;
• Indication of pulmonary hypertension on 2 separate echocardiogram examinations;
• Patients who plan to return to resource poor areas/countries.
• Between the ages of birth and 40 years.
• Women of childbearing potential must have a negative pregnancy test.

You may not qualify if:

• Patient with biopsy proven chronic active hepatitis or fibrosis with portal bridging.
• Patient with SCD chronic lung disease \> stage 3 (see Appendix 1).
• Patient with severe renal dysfunction defined as creatinine clearance \< 40 mL/min/1.73 M\^2.
• Patient with severe cardiac dysfunction defined as echocardiogram shortening fraction \< 25% or NYHA class III or IV.
• Patient with HIV infection.
• Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate bone marrow transplantation.
• Patient or patient's guardian(s) unable to understand the nature and risks inherent in the BMT process.
• Pregnant/lactating women and those unwilling to use acceptable contraception will be excluded.
• 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.

Sponsors & Collaborators

• Tami D. John: lead
• Baylor College of Medicine: collaborator
• The Methodist Hospital Research Institute: collaborator

Study Sites (2)

Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Hemoglobin SC Disease; Anemia

Interventions

Busulfan; Alemtuzumab; Cyclophosphamide; Mesna

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Sulfhydryl Compounds

Results Point of Contact

• Title: Dr. Tami D. John
• Organization: Baylor College of Medicine/Texas Children's Hospital

tdjohn@texaschildrens.org

832-824-4723

Study Officials

• Tami John, MD

  Baylor College of Medicine - Texas Children's Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, Pediatrics-Hema & Oncology

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 21, 2007
• Study Start: July 1, 2005
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: July 31, 2020
• Results First Posted: July 31, 2020

Record last verified: 2020-07

Locations

US (2)