Purine Analog-Based Conditioning in Patients With Severe Aplastic Anemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00427336
First received: January 25, 2007
Last updated: September 20, 2011
Last verified: September 2011

January 25, 2007
September 20, 2011
December 2000
August 2009   (final data collection date for primary outcome measure)
Number of Patients With Engraftment Response [ Time Frame: First 100 days post transplant. ] [ Designated as safety issue: Yes ]
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%)
Not Provided
Complete list of historical versions of study NCT00427336 on ClinicalTrials.gov Archive Site
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Purine Analog-Based Conditioning in Patients With Severe Aplastic Anemia
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.

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.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Aplastic Anemia
  • Drug: Fludarabine
    30 mg/m^2 by vein daily over 30 minutes
    Other Names:
    • Fludarabine Phosphate
    • Fludara
  • 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
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
Interventions:
  • Drug: Fludarabine
  • Drug: Cyclophosphamide
  • Drug: Antithymocyte Globulin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
9
August 2009
August 2009   (final data collection date for primary outcome measure)

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.
Both
up to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00427336
IDP00-266
No
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
Not Provided
Principal Investigator: Paolo Anderlini, MD M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
September 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP