Purine Analog-Based Conditioning in Patients With Severe Aplastic Anemia

September 20, 2011 updated by: M.D. Anderson Cancer Center

Purine Analog-Based Conditioning for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • U.T.M.D. Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: Fludarabine
30 mg/m^2 by vein daily over 30 minutes
Other Names:
  • Fludara
  • Fludarabine Phosphate
Drug: Cyclophosphamide
300 mg/m^2 by vein daily over 2 hours
Other Names:
  • Cytoxan
  • Neosar
Drug: Antithymocyte Globulin
3.75 mg/kg by vein daily over 4 hours
Other Names:
  • ATG
  • Thymoglobulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Engraftment Response
Time Frame: First 100 days post transplant.
Engraftment defined as (1) the first of three consecutive days of an Absolute neutrophil count (ANC) >500/mL (b) the first of seven consecutive days of an unsupported platelet count 20,000. Patient needs to survive at least 28 days to be evaluable for engraftment. Chimerism studies need to demonstrate donor-derived hematopoiesis (>90%)
First 100 days post transplant.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Investigators

  • Principal Investigator: Paolo Anderlini, MD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2000

Primary Completion (Actual)

August 1, 2009

Study Completion (Actual)

August 1, 2009

Study Registration Dates

First Submitted

January 25, 2007

First Submitted That Met QC Criteria

January 26, 2007

First Posted (Estimate)

January 29, 2007

Study Record Updates

Last Update Posted (Estimate)

October 27, 2011

Last Update Submitted That Met QC Criteria

September 20, 2011

Last Verified

September 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IDP00-266

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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