Aplastic AnemiaNCT00427336
Purine Analog-Based Conditioning in Patients With Severe Aplastic Anemia
A study testing Fludarabine, Cyclophosphamide and Antithymocyte Globulin in people with Aplastic Anemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 70 years
- Conditions the study is for
- Aplastic Anemia
- What is being tested?
- Fludarabine, Cyclophosphamide and Antithymocyte Globulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2000to Aug 2009
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Life expectancy of less than 8 weeks. Inability to provide informed consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
U.T.M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Purine Analog-Based Conditioning for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia
Primary Objectives:
- 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).
- To determine the engraftment kinetics and degree of chimerism that can be achieved with this strategy.
Read the 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.
- Conditions
- Aplastic Anemia
- Being tested
- Fludarabine, Cyclophosphamide, Antithymocyte Globulin
- Keywords
- Severe Aplastic Anemia, Bone Marrow Failure, Stem Cell Transplantation, Fludarabine, Cyclophosphamide, Antithymocyte Globulin, SAA, ATG, Cytoxan, Neosar, Fludarabine Phosphate, Thymoglobulin
- Medical subject headings
- Anemia, Aplastic, Bone Marrow Failure Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Also called Fludarabine Phosphate, Fludara
30 mg/m^2 by vein daily over 30 minutes
CyclophosphamideDrug
Also called Cytoxan, Neosar
300 mg/m^2 by vein daily over 2 hours
Antithymocyte GlobulinDrug
Also called ATG, Thymoglobulin
3.75 mg/kg by vein daily over 4 hours
| Study group | Role | What they receive |
|---|---|---|
| Fludarabine + Cyclophosphamide + ATG | Experimental | 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 Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Antithymocyte Globulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Engraftment Response
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%)
Measured: First 100 days post transplant.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2007 (estimated)
- Study startDec 2000
- Primary completionAug 2009
- Study completionAug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paolo Anderlini, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00427336
- Sponsor's protocol ID
- IDP00-266
- Status last verified
- Sep 2011
- First submitted
- 25 Jan 2007
- Last updated
- 27 Oct 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Purine Analog-Based Conditioning for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia
- ClinicalTrials.gov ID
- NCT00427336
- Acronym / sponsor ID
- IDP00-266
- Conditions
- Aplastic Anemia
- Keywords
- Severe Aplastic Anemia, Bone Marrow Failure, Stem Cell Transplantation, Fludarabine, Cyclophosphamide, Antithymocyte Globulin, SAA, ATG
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Dec 2000
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 29 Jan 2007 (estimated)
- Results
- Posted 27 Oct 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objectives:
- 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).
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fludarabine + Cyclophosphamide + ATG | Experimental | Drug: Fludarabine, Drug: Cyclophosphamide, Drug: Antithymocyte GlobulinFludarabine 30 mg/m^2/day by vein (IV), Cyclophosphamide IV 300 mg/m^2/day, ATG (Antithymocyte Globulin) IV 3.75 mg/kg/day |
Who may qualify
- Ages
- Up to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (1 listed)
- Life expectancy of less than 8 weeks. Inability to provide informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FludarabineAlso: Fludarabine Phosphate, Fludara30 mg/m^2 by vein daily over 30 minutes | Drug | Fludarabine + Cyclophosphamide + ATG |
| CyclophosphamideAlso: Cytoxan, Neosar300 mg/m^2 by vein daily over 2 hours | Drug | Fludarabine + Cyclophosphamide + ATG |
| Antithymocyte GlobulinAlso: ATG, Thymoglobulin3.75 mg/kg by vein daily over 4 hours | Drug | Fludarabine + Cyclophosphamide + ATG |
Primary outcome
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%)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The University of Texas M.D.Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paolo Anderlini, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fludarabine, Cyclophosphamide and Antithymocyte Globulin in people with Aplastic Anemia, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Oct 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Engraftment Response (time frame: First 100 days post transplant.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2011.