Severe Aplastic AnemiaNCT01129323
Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia
A study testing Cyclophosphamide, Fludarabine, Rabbit ATG in people with Severe Aplastic Anemia, run by City of Hope Medical Center.
Trial summary
The purpose of this study is to evaluate the effectiveness of allogeneic transplant after a reduced-intensity preparative regimen for patient, to evaluate survival, and to evaluate the side effects of this treatment. The patient will be in the study for two years for treatment and active monitoring. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Severe Aplastic Anemia
- What is being tested?
- Cyclophosphamide, Fludarabine, Rabbit ATG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2009to Sep 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 21 years old or younger
- Male or female recipients must have histopathologically confirmed diagnosis of severe aplastic anemia. Diagnostic Criteria for Server Aplastic Anemia will be based on the definitions set forth by the international Aplastic Anemia Study Group
- At least two of the following:
- Absolute neutrophil count <0.5 x 109/L Platelet count <20 x 109 /L Anemia with corrected reticulocyte count <1%
- AND
- Bone marrow cellularity <25%, or bone marrow cellularity <50% with fewer than 30% hematopoietic cell
- Availability of an HLA identical sibling
Who cannot join
- Active and uncontrolled infection
- HIV-1 infection
- Pregnancy or breastfeeding.
- DLCO <40% predicted
- Left Ventricular Ejection Fraction < 40%
- Performance scale Karnofsky <=40% or Lansky<=40% for patients <16 years old
About this study
The purpose of this study is to evaluate the effectiveness of allogeneic transplant after a reduced-intensity preparative regimen for patient, to evaluate survival, and to evaluate the side effects of this treatment. The patient will be in the study for two years for treatment and active monitoring. After treatment and active monitoring are over, the patient's medical condition will be followed indefinitely.
Read the detailed description
Aplastic Anemia is a blood disorder where bone marrow does not produce enough cells for blood. Patients with aplastic anemia have lower counts of all three blood cell types (RBC, WBC, and Platelet). Severe cases of aplastic anemia that are untreated can lead to death from bleeding and overwhelming infection.
For patients with Severe Aplastic Anemia (SAA), allogeneic hematopoietic stem cell transplant (HSCT) from an HLA-identical sibling is an accepted treatment for restoring normal bone marrow function. Preparative regimens for allogeneic HSCT are designed to give the highest tolerated doses of chemotherapy, with or without total body irradiation (TBI), in order to fully "ablate" or destroy the patient host's bone marrow so that the transplanted cells from the HLA-identical sibling can engraft in the patient host.
While allogeneic HSCT has been proven to be a curative form of therapy for SAA, it is also associated with high transplant-related morbidity (side effects) and possible mortality (death). One of the toxic side effects from high-dose chemotherapy and TBI are believed to be a major contributing factor to "Graft-versus-Host Disease" (GVHD).
Preliminary studies have shown that a reduced intensity (non-myeloablative) allogeneic HSCT may be just as effective in treating SAA. Low-dose chemotherapy is used instead of high-dose chemotherapy and TBI. Some smaller studies have indicated that reduced intensity preparative regimens using Fludarabine and Cyclophosphamide allowed engraftment in the matched sibling donor setting with an acceptable level of toxic side effects in subjects with a variety of hematologic cancers. Additional studies that followed showed that a reduced intensity preparative regimen that included fludarabine, cyclophosphamide and antithymocyte globulin, allowed engraftment of donor stem cells in subjects with SAA with acceptable engraftment rates and a decrease in the severity of GVHD.
This study is designed to evaluate the effectiveness of allogeneic transplant after a reduced-intensity preparative regimen, to evaluate survival, and to evaluate the side effects including GVHD of this treatment. Patients will be in the study for two years for treatment and active monitoring. All patients will be followed until death.
- Conditions
- Severe Aplastic Anemia
- Being tested
- Cyclophosphamide, Fludarabine, Rabbit ATG
- Keywords
- Anemia, Severe, Aplastic, Reduced-Intensity, Allogeneic, Stem, Cell, Transplantation
- Medical subject headings
- Anemia, Aplastic, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclophosphamide, Fludarabine, Rabbit ATGDrug
Fludarabine 30mg/m2/dose IV and cyclophosphamide 10mg/kg/dose IV are given once per day from day -5 to -2. rATG 1.5 mg/kg/dose IV is given from day -4 to -1.
| Study group | Role | What they receive |
|---|---|---|
| Reduced-Intensity Preparative Regimen for Allogeneic SCT | Experimental | Patient in this arm will receive maximally tolerated (reduced) doses of cytotoxic therapy with the goals of suppressing the immune system, and ablate host hematopoiesis to ensure engraftment of the donor's hematopoietic system. Receives: Drug: Cyclophosphamide, Fludarabine, Rabbit ATG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Engraftment rate
Measured: Day 42 after allogeneic transplant
Secondary outcomes (6)
Relapse
Measured: Days 180, 365 and yearly post transplant
Development of Graft vs. Host Disease
Measured: Days 180, 365 and yearly post transplant
Evaluation of the occurrence of secondary malignancies
Measured: Days 180, 365 and yearly post transplant
Overall survival
Measured: Days 180, 365 and yearly post transplant
Evaluation of treatment feasibility
Measured: Days 180, 365 and yearly post transplant
Evaluation of toxicities
Measured: Days 180, 365 and yearly post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2010 (estimated)
- Study startNov 2009
- Primary completionSep 2011
Why it stopped: This study did not accrue any subjects and due to this will be closed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anna Pawlowska, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01129323
- Sponsor's protocol ID
- 07081
- Status last verified
- Mar 2012
- First submitted
- 21 Apr 2010
- Last updated
- 27 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia
- ClinicalTrials.gov ID
- NCT01129323
- Acronym / sponsor ID
- 07081
- Conditions
- Severe Aplastic Anemia
- Keywords
- Anemia, Severe, Aplastic, Reduced-Intensity, Allogeneic, Stem, Cell, Transplantation
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: This study did not accrue any subjects and due to this will be closed.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Study start
- Nov 2009
- Primary completion
- Sep 2011 (actual)
- First posted
- 24 May 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the effectiveness of allogeneic transplant after a reduced-intensity preparative regimen for patient, to evaluate survival, and to evaluate the side effects of this treatment. The patient will be in the study for two years for treatment and active monitoring. After treatment and active monitoring are over, the patient's medical condition will be followed indefinitely.
Detailed description
Aplastic Anemia is a blood disorder where bone marrow does not produce enough cells for blood. Patients with aplastic anemia have lower counts of all three blood cell types (RBC, WBC, and Platelet). Severe cases of aplastic anemia that are untreated can lead to death from bleeding and overwhelming infection.
For patients with Severe Aplastic Anemia (SAA), allogeneic hematopoietic stem cell transplant (HSCT) from an HLA-identical sibling is an accepted treatment for restoring normal bone marrow function. Preparative regimens for allogeneic HSCT are designed to give the highest tolerated doses of chemotherapy, with or without total body irradiation (TBI), in order to fully "ablate" or destroy the patient host's bone marrow so that the transplanted cells from the HLA-identical sibling can engraft in the patient host.
While allogeneic HSCT has been proven to be a curative form of therapy for SAA, it is also associated with high transplant-related morbidity (side effects) and possible mortality (death). One of the toxic side effects from high-dose chemotherapy and TBI are believed to be a major contributing factor to "Graft-versus-Host Disease" (GVHD).
Preliminary studies have shown that a reduced intensity (non-myeloablative) allogeneic HSCT may be just as effective in treating SAA. Low-dose chemotherapy is used instead of high-dose chemotherapy and TBI. Some smaller studies have indicated that reduced intensity preparative regimens using Fludarabine and Cyclophosphamide allowed engraftment in the matched sibling donor setting with an acceptable level of toxic side effects in subjects with a variety of hematologic cancers. Additional studies that followed showed that a reduced intensity preparative regimen that included fludarabine, cyclophosphamide and antithymocyte globulin, allowed engraftment of donor stem cells in subjects with SAA with acceptable engraftment rates and a decrease in the severity of GVHD.
This study is designed to evaluate the effectiveness of allogeneic transplant after a reduced-intensity preparative regimen, to evaluate survival, and to evaluate the side effects including GVHD of this treatment. Patients will be in the study for two years for treatment and active monitoring. All patients will be followed until death.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Reduced-Intensity Preparative Regimen for Allogeneic SCT | Experimental | Drug: Cyclophosphamide, Fludarabine, Rabbit ATGPatient in this arm will receive maximally tolerated (reduced) doses of cytotoxic therapy with the goals of suppressing the immune system, and ablate host hematopoiesis to ensure engraftment of the donor's hematopoietic system. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- 21 years old or younger
- Male or female recipients must have histopathologically confirmed diagnosis of severe aplastic anemia. Diagnostic Criteria for Server Aplastic Anemia will be based on the definitions set forth by the international Aplastic Anemia Study Group
- At least two of the following:
- Absolute neutrophil count <0.5 x 109/L Platelet count <20 x 109 /L Anemia with corrected reticulocyte count <1%
- AND
Key exclusion criteria (6 listed)
- Active and uncontrolled infection
- HIV-1 infection
- Pregnancy or breastfeeding.
- DLCO <40% predicted
- Left Ventricular Ejection Fraction < 40%
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 |
|---|---|---|
| Cyclophosphamide, Fludarabine, Rabbit ATGFludarabine 30mg/m2/dose IV and cyclophosphamide 10mg/kg/dose IV are given once per day from day -5 to -2. rATG 1.5 mg/kg/dose IV is given from day -4 to -1. | Drug | Reduced-Intensity Preparative Regimen for Allogeneic SCT |
Primary outcome
Engraftment rate
Time frame: Day 42 after allogeneic transplant
6 secondary outcomes
Relapse
Time frame: Days 180, 365 and yearly post transplant
Development of Graft vs. Host Disease
Time frame: Days 180, 365 and yearly post transplant
Evaluation of the occurrence of secondary malignancies
Time frame: Days 180, 365 and yearly post transplant
Overall survival
Time frame: Days 180, 365 and yearly post transplant
Evaluation of treatment feasibility
Time frame: Days 180, 365 and yearly post transplant
Evaluation of toxicities
Time frame: Days 180, 365 and yearly post transplant
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2012.
Related trials for Severe Aplastic Anemia
RecruitingPhase 2
Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes Using G-CSF Mobilized CD34+ Selected Hematopoietic Precursor Cells Co-Infused With a Reduced Dose of Non-Mobilized Donor T-cells
Severe Aplastic Anemia, MDS (Myelodysplastic Syndrome)
RecruitingPhase 1/2
A Phase 1/2 Study to Evaluate the Safety and Efficacy of Dibotatug (DR-01) in Adults With Bone Marrow Failure Syndromes
Bone Marrow Failure Syndromes, Aplastic Anemias
Active, not recruitingPhase 2
Standard Immunosuppressive Therapy Combined With Romiplostim N01 as First-line Treatment for Severe Aplastic Anemia
Aplastic Anemia, TPO Receptor Agonists
RecruitingObservational study
Natural History of Acquired and Inherited Bone Marrow Failure Syndromes
Severe Aplastic Anemia, Telomere Biology Disorders
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
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.
Anna Pawlowska, MD principal investigator
City of Hope Medical Center
Questions about this trial
What is this clinical trial studying?
A study testing Cyclophosphamide, Fludarabine, Rabbit ATG in people with Severe Aplastic Anemia, run by City of Hope Medical Center.
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 7 inclusion and 6 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: withdrawn, as of the sponsor's last update on 27 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Engraftment rate (time frame: Day 42 after allogeneic 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 Mar 2012.