Purine Analog-Based Conditioning for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia
Purine Analog-Based Conditioning in Patients With Severe Aplastic Anemia
Sponsors
Source
M.D. Anderson Cancer Center
Oversight Info
Has Dmc
No
Brief Summary
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
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.
Overall Status
Completed
Start Date
2000-12-01
Completion Date
2009-08-01
Primary Completion Date
2009-08-01
Phase
N/A
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Number of Patients With Engraftment Response |
First 100 days post transplant. |
Enrollment
9
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
30 mg/m^2 by vein daily over 30 minutes
Arm Group Label
Fludarabine + Cyclophosphamide + ATG
Other Name
Fludarabine Phosphate
Fludara
Intervention Type
Drug
Intervention Name
Description
300 mg/m^2 by vein daily over 2 hours
Arm Group Label
Fludarabine + Cyclophosphamide + ATG
Other Name
Cytoxan
Neosar
Intervention Type
Drug
Intervention Name
Description
3.75 mg/kg by vein daily over 4 hours
Arm Group Label
Fludarabine + Cyclophosphamide + ATG
Other Name
ATG
Thymoglobulin
Eligibility
Criteria
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.
Gender
All
Minimum Age
N/A
Maximum Age
70 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Paolo Anderlini, MD |
Principal Investigator |
M.D. Anderson Cancer Center |
Location
Facility |
|
U.T.M.D. Anderson Cancer Center Houston Texas 77030 United States |
Location Countries
Country
United States
Verification Date
2011-09-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Condition Browse
Number Of Arms
1
Intervention Browse
Mesh Term
Cyclophosphamide
Fludarabine phosphate
Thymoglobulin
Antilymphocyte Serum
Fludarabine
Vidarabine
Arm Group
Arm Group Label
Fludarabine + Cyclophosphamide + ATG
Arm Group Type
Experimental
Description
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
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
January 25, 2007
Study First Submitted Qc
January 26, 2007
Study First Posted
January 29, 2007
Last Update Submitted
September 20, 2011
Last Update Submitted Qc
September 20, 2011
Last Update Posted
October 27, 2011
Results First Submitted
September 20, 2011
Results First Submitted Qc
September 20, 2011
Results First Posted
October 27, 2011
ClinicalTrials.gov processed this data on August 29, 2018
Conditions
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conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.