Purine Analog-Based Conditioning in Patients With Severe Aplastic Anemia

NCT ID: NCT00427336

Last Updated: 2011-10-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-12-31

Study Completion Date

2009-08-31

Brief Summary

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Primary Objectives:

1. To determine the feasibility and toxicity of employing purine-analog based conditioning for allogeneic donor stem cell transplantation in patients with severe aplastic anemia (AA).
2. To determine the engraftment kinetics and degree of chimerism that can be achieved with this strategy.

Detailed Description

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Before treatment starts, patients will have their bone marrow checked and will have lung, heart, and kidney tests.

Patients in this study will receive the drugs fludarabine, cyclophosphamide, and antithymocyte globulin by vein through a previously inserted plastic catheter that extends into the large chest vein. Fludarabine will be given daily for four days, cyclophosphamide will given daily for four days, and antithymocyte globulin will be given daily for four days (three days for related donor transplants).

Two days after the last dose of cyclophosphamide, donor marrow or stem cells will be infused through a catheter (thin plastic tube). Drugs will be given to lower the chance of an allergic reaction to the stem cells. Patients will also get shots of filgrastim (a drug that helps white blood cell growth) and antibiotics by mouth. The blood cell counts will fall to low levels during the first 2 weeks when patients may need transfusions of red blood cells and platelets. The chemotherapy will be given in the hospital. After the infusion of stem cells, patients will be monitored in the hospital. They will later be closely followed as outpatients and will be required to remain in the Houston area for about three months after the transplant.

Drugs (cyclosporine and methotrexate) to lower the chance of graft-versus-host disease will be given. Cyclosporine will be given as a continuous infusion starting 2 days before transplantation. Methotrexate will be given through the catheter on Days 1, 3, 6 and 11 after transplantation. Cyclosporine will be given as pills when the patient is able to swallow. Cyclosporine will be continued for no less than 6 months after transplantation after which it will be gradually stopped. The drug tacrolimus may be used instead of cyclosporine.

Blood, urine, bone marrow, and x-ray exams will be done as needed to monitor the results of bone marrow transplantation. Patients may require blood and platelet transfusions. Blood tests will be done daily while hospitalized and several times a week until the blood counts recover. Bone marrow aspiration and biopsies will be performed before the transplant, when the donated cells show signs of engraftment, and at other times during the next 1 to 3 years. They will be done to evaluate the growth of the transplant marrow, possible recurrence of malignancy, and recovery of immunity. If this treatment proves unsuccessful in more than three of the first ten patients, the study will be stopped.

This is an investigational study. The FDA has approved all of the drugs in this study for other indications. Up to 30 patients will be treated on this study. All will be enrolled at M.D. Anderson.

Conditions

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Aplastic Anemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Fludarabine + Cyclophosphamide + ATG

Fludarabine 30 mg/m\^2/day by vein (IV), Cyclophosphamide IV 300 mg/m\^2/day, ATG (Antithymocyte Globulin) IV 3.75 mg/kg/day

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

30 mg/m\^2 by vein daily over 30 minutes

Cyclophosphamide

Intervention Type DRUG

300 mg/m\^2 by vein daily over 2 hours

Antithymocyte Globulin

Intervention Type DRUG

3.75 mg/kg by vein daily over 4 hours

Interventions

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Fludarabine

30 mg/m\^2 by vein daily over 30 minutes

Intervention Type DRUG

Cyclophosphamide

300 mg/m\^2 by vein daily over 2 hours

Intervention Type DRUG

Antithymocyte Globulin

3.75 mg/kg by vein daily over 4 hours

Intervention Type DRUG

Other Intervention Names

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Fludarabine Phosphate Fludara Cytoxan Neosar ATG Thymoglobulin

Eligibility Criteria

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Inclusion Criteria

* Patients up to 70 years of age with a diagnosis of severe AA (Camitta et al., 1979) and a matched unrelated donor who are unresponsive to IS or who have relapsed after an initial response to IS. Patients with a diagnosis of SAA and an human leukocyte antigen (HLA) - compatible sibling donor are eligible only if they are 40 years of age or older (up to age 70) and regardless whether they have received IS or not. Patients with primary or secondary graft failure following autologous or allogeneic stem cell transplant are eligible.
* Patients must have a serum bilirubin of 2 mg/dl or less, serum creatinine \< 2.0 mg/dl, no symptomatic cardiac or pulmonary disease and a PS of no more than 2. Life expectancy not severely limited by concomitant illness (\> 12 weeks). Left ventricular ejection fraction \> 40%, no uncontrolled arrhythmia or symptomatic cardiac disease. Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) \> 40%. No symptomatic pulmonary disease. Negative pregnancy test.
* Patients must have an HLA-compatible related or unrelated donor willing to donate marrow or rhG-CSF-mobilized peripheral blood stem cells. In the event of transplants from matched unrelated donors, a high-resolution allele match for HLA-A, -B, -C, -DRB1 and DQB1 ("10 of 10 match") is preferred. However, a one-antigen mismatch ("micromismatch") is also considered acceptable matching ("9 of 10 match").
* Patients must sign informed consent. In the event of a pediatric patient (i.e., a minor), consent will be provided by their guardian/parent.
* Lack of clonal cytogenetic abnormalities associated with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or other hematologic malignancies.

Exclusion Criteria

* Life expectancy of less than 8 weeks. Inability to provide informed consent.
Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paolo Anderlini, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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U.T.M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://www.mdanderson.org

The University of Texas M.D.Anderson Cancer Center

Other Identifiers

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IDP00-266

Identifier Type: -

Identifier Source: org_study_id