Allogeneic Stem Cell Transplant for Patients With Severe Aplastic Anemia

This study has been terminated.
Sponsor:
Collaborators:
The Methodist Hospital System
Texas Children's Hospital
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
Kathryn Leung, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00578903
First received: December 19, 2007
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

Patients have been diagnosed with severe Aplastic Anemia that have not responded to treatment with immunosuppressive therapy (drugs that suppress the immune system, for example Steroids). The immune system is the system in the body that helps protect the body and fights bacterial, viral and fungal infections.

Research studies have shown that patients with Aplastic Anemia have improved survival (may live longer) after receiving a HLA (Human Leukocyte Antigen) identical sibling (brother and sister) stem cell transplants. Patients who do not have matched siblings can undergo immunosuppressive therapy, which has also shown to improve outcome. Unfortunately patients who do not respond to immunosuppressive therapy usually die. The best chance of survival for these patients is an HLA matched unrelated or mismatched related stem cell transplant as described below.

Stem cells are created in the bone marrow. They mature into different types of blood cells that people need including red blood cells which carry oxygen around the body, white blood cells which help fight infections, and platelets which help the blood to clot and prevent bleeding. For a matched unrelated stem cell transplant, stem cells are collected from a person (donor) who is not related to the patient but who has the same type of stem cells. For a mismatched related stem cell transplant, stem cells are collected from a donor who is related to the patient and whose stem cells are almost the same as those of the patient but not exactly. The patient then receives high dose chemotherapy. This chemotherapy kills the stem cells in the patient's bone marrow. Stem cells that have been collected from the donor are then given to the patient to replace the stem cells that have been killed.

The major problems associated with these types of stem cell transplants are graft rejection (where the patient's immune system rejects the donor stem cells) and severe graft versus host disease (GVHD), where the donors stem cell reacts against the patient's tissues in the body.


Condition Intervention Phase
Aplastic Anemia
Drug: Cytoxan
Drug: Campath
Radiation: Total Body Irradiation (TBI)
Drug: FK-506
Drug: Methotrexate
Procedure: Stem cell infusion
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Stem Cell Transplantation for Patients With Severe Aplastic Anemia, Using Matched Unrelated Donors and Mismatched Related Donors (SAA MUD)

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Number of Subjects Alive at 100 Days Post Transplant [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of Patients With Engraftment Rate at 100 Days Post Transplant [ Time Frame: 100 days post transplant ] [ Designated as safety issue: Yes ]
    Absolute neutrophil count greater than 0.5 X 109/ml for at least 3 days

  • Number of Patients With Acute GVHD at 100 Days Post Transplant [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Number of Patients With Chronic GVHD at 2 Years Post Transplant [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Number of Subjects Alive at 1 Year Post Transplant [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Number of Subjects Alive at 2 Years Post Transplant [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: February 2002
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patients

Patients with a diagnosis of severe aplastic anemia who require an allogeneic stem cell transplant but lack an Human Leukocyte Antigen (HLA) identical family member.

Cytoxan, Campath, TBI-Total Body Irradiation, FK-506, Methotrexate, Stem Cell Infusion

Drug: Cytoxan
Cytoxan will be given at 50 mg/kg per dose for 4 successive days.
Other Name: Cyclophosphamide
Drug: Campath
Campath will be given at a dose of 3 mg for patients whose weight is between 5 and 15 kg; at a dose of 5 mg for patients whose weight is between 16 and 30 kg; and at a dose of 10 mg for patients whose weight is greater than 30 kg. The last dose of Campath should be 24 hours or more before stem cell infusion.
Other Name: alemtuzumab
Radiation: Total Body Irradiation (TBI)
TBI will be given at a dose of 200 cGy for 6/6 HLA match and at a dose of 400 cGy in two fractions of 200 cGy each for 5/6 HLA matched donor.
Other Name: Irradiation
Drug: FK-506
FK-506 will be given at a dose of 0.03 mg/kg/day via continuous infusion over 24 hours from 4pm on day -2 until engraftment or when patient is able to take by mouth (PO), then 0.03 mg/kg PO every 12 hours.
Other Name: Tacrolimus
Drug: Methotrexate
Methotrexate will be administered on day +1, day +3, day +6 and day +11 at a dose of 5 mg/m2. The day +11 dose may be omitted at the discretion of the bone marrow transplant (BMT) in-patient attending physician.
Other Name: Methotrexate
Procedure: Stem cell infusion
Where possible patients will receive bone marrow. Marrow will be collected as per National Marrow Donor Program (NMDP) guidelines to provide a volume of 15-20 ml/kg of marrow and/or 2-4 X 10^8 nucleated cells/kg. In case marrow cannot be collected, peripheral blood stem cell (PBSC) will be substituted. A minimum of 5-6 X 10^6 CD 34+ cells/kg should be collected, with a target of 10 X 10^6/kg.
Other Name: Stem Cell Infusion

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of Severe Aplastic Anemia (SAA) based on bone marrow aspirate and biopsy results.
  2. Failure to respond to immunosuppressive therapy.
  3. Lack of an Human Leukocyte Antigen (HLA) identical family member.
  4. A 6/6 or 5/6 HLA matched unrelated donor or a 5/6 matched related donor available after high resolution HLA typing.
  5. Age from birth to 60 years.

Exclusion Criteria:

  1. Severe disease other than aplastic anemia that would limit the probability of survival during the graft procedure. Patients who present with active infection must be treated to maximally resolve this problem before beginning the conditioning regimen.
  2. Human immunodeficiency virus (HIV) seropositive patients
  3. Patients who have clonal cytogenetic abnormalities or a myelodysplastic syndrome.
  4. Patient greater than 60 years of age.
  5. Women who are pregnant or nursing.
  6. Patients with active hepatitis
  7. Patients with severe cardiac dysfunction defined as shortening fraction < 25%.
  8. Patients with severe renal dysfunction defined as creatinine clearance < 40 ml/mim/1.73m2.
  9. Patient with severe pulmonary dysfunction with forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) 40% of predicted or 3 standard deviations (SD) below normal.
  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: NCT00578903

Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
The Methodist Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
The Methodist Hospital System
Texas Children's Hospital
Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
Principal Investigator: Kathryn Leung, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Kathryn Leung, Principal Investigator, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00578903     History of Changes
Obsolete Identifiers: NCT00598221
Other Study ID Numbers: 10915-SAA MUD, SAA MUD
Study First Received: December 19, 2007
Results First Received: August 4, 2013
Last Updated: January 21, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
Severe Aplastic Anemia
Severe

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014