Allogeneic Stem Cell Transplant for Patients With Severe Aplastic Anemia

Summary

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.

Conditions

• Aplastic Anemia

Interventions

DRUG

Cytoxan

Cytoxan will be given at 50 mg/kg per dose for 4 successive days.

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.

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.

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.

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.

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.

Sponsors & Collaborators

• The Methodist Hospital Research Institute

  collaborator OTHER

• Center for Cell and Gene Therapy, Baylor College of Medicine

  collaborator OTHER

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Kathryn Leung, MD · Baylor College of Medicine

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Minute

Max Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2002-02-28

Primary Completion

2012-07-31

Completion

2012-07-31

Countries

• United States

Study Locations