Genetic DisordersPhase 2NCT00578435
Allogeneic Bone Marrow Transplantation for the Treatment of Genetic Disorders of Erythropoiesis
A Phase 2 study testing Busulfan, Cyclophosphamide, BMD in people with Genetic Disorders and Sickle Cell Anemia, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to determine and confirm the role of bone marrow transplantation in the treatment of disorders of the red cell and hemoglobin including sickle cell anemia, thalassemia and diamond blackfan anemia. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Genetic Disorders, Sickle Cell Anemia
- What is being tested?
- Busulfan, Cyclophosphamide, BMD
- Type of treatment
- Surgery or procedure
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 1994to Aug 2008
- Phase
- Phase 2
- 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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with severe HOMOZYGOUS SICKLE CELL ANEMIA or SICKLE/BETA THALASSEMIA
- Neurologic event (stroke or hemorrhage).
- Abnormal cerebral MRI scan and cerebral arteriogram or MRI angiographic study (MRA) and impaired neuropsychologic testing.
- Recurrent acute chest syndrome (> 2 episodes)
- Stage I-II sickle chronic lung disease
- Sickle cell nephropathy (moderate or severe proteinuria or GFR 30-50% of predicted for age.
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- Major visual impairment in at least one eye with bilateral proliferative retinopathy.
- Osteonecrosis of multiple bones
- Chronic debilitating pain secondary to vasoocclusive crisis (>= 3 episodes per year for >= 3 years) Recurrent priapism
- Allo-immunization with the development of antibodies following chronic transfusion therapy
- Patients with HOMOZYGOUS SICKLE CELL ANEMIA or SICKLE/BETA THALASSEMIA with the following criteria will be considered for accrual on this protocol
- Patients < 2 years with high WBC counts and/or >1 episode of dactylitis and/or a Hgb < 7 g/dl
- History of death from sickle cell disease in sibship of patient
- Patients with BETA-THALASSEMIA MAJOR with Lucarelli class 1 or 2 risk status i.e with only 0-2 of the following factors: hepatomegaly, portal fibrosis, or poor chelation therapy
- Patients with DIAMOND-BLACKFAN ANEMIA who have failed conventional therapy.
- Patients must have an HLA-compatible related donor. The donor must be healthy and able to undergo general anesthesia. Donors with heterozygous sickle cell anemia (hemoglobin AS) or with heterozygous thalassemia are acceptable donors.
- At the time of referral for transplantation, patients must be in good clinical condition without any evidence of infections and a Karnofsky or Lansky pediatric performance scale > 70%
- Each patient and donor must be willing to participate as a research subject and must sign an informed consent form after having been advised as to the nature and risk of the study prior to entering the protocol. Parents or legal guardians of patients who are minor will sign the consent form after being advised of the nature and risks of the study
Who cannot join
- Patients whose life expectancy is less than 8 weeks. Patients with a Karnofsky or Lansky performance score of < 70%
- Patients with severe major organ dysfunction:
- Patients with severe renal impairment. This will be determined by a creatinine clearance < 70 ml/min/1.73 m2 (or serum creatinine > 1.5 x Normal) or by a glomerular filtration rate < 30% of predicted normal for age
- Inadequate cardiac function as determined by fractional shortening < 28% on echocardiogram, and/or ejection fraction of < 50% on echocardiogram or RNCA.
- Patients with FS of 23-28% who show an increase in FS in response to stress on the supine bicycle ergometer are eligible
- Major liver dysfunction: SGOT > 3 x upper limit of normal. Hyperbilirubinemia will not be used as an exclusion criteria because of the hemolytic component of the bilirubin. Patients with active hepatitis or severe liver fibrosis will also be excluded
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- Severe residual functional neurologic impairment
- Stage III-IV sickle chronic lung disease
- Pregnant or lactating women are excluded
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
The purpose of this study is to determine and confirm the role of bone marrow transplantation in the treatment of disorders of the red cell and hemoglobin including sickle cell anemia, thalassemia and diamond blackfan anemia.
Read the detailed description
The trial proposed is a single armed phase II treatment protocol designed to examine the engraftment,toxicity and graft-versus-host disease following a novel cytoreductive regimen including cyclophosphamide and Busulfan for the treatment of patients with Severe Sickle Cell Anemia,Thalassemia, and Diamond Blackfan Anemia using stem cell transplants derived from HLA-genotypically identical siblings.
Patients will be conditioned for transplantation with cyclophosphamide (50 mg/kg/day x 4 days), and busulfan [(if < 4 years of age 1 mg/kg 4 times per day x 4 days), (if > 4 years of age 0.8 mg/kg 4 times per day x 4 days)]. Patients will receive Methotrexate \& Cyclosporin-A for prophylaxis against GvHD and GCSF to promote engraftment.
The preferred source of stem cells from related HLA-matched related donors will be unmodified bone marrow stem cells.
- Conditions
- Genetic Disorders, Sickle Cell Anemia
- Being tested
- Busulfan, Cyclophosphamide, BMD
- Keywords
- ERYTHROPOIESIS, Genetic Disorders, Sickle Cell Anemia, Thalassemia, Diamond Blackfan Anemia
- Medical subject headings
- Genetic Diseases, Inborn, Anemia, Sickle Cell, Thalassemia, Anemia, Diamond-Blackfan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Busulfan, Cyclophosphamide, BMDProcedure or surgery
Busulfan 0.8 or 1 mg/Kg/day Days 8-6 Cyclophosphamide 50 mg/Kg/day Days 2-5 BMT Day 0
What is being measured
The primary outcome is the main question the study is designed to answer.
Define the role of bone marrow transplantation for the treatment of sickle cell disease and the reversibility of sickle cell vasculopathy and organ damage, good risk thalassemia major and Diamond-Blackfan Anemia.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2007 (estimated)
- Study startJan 1994
- Primary completionAug 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Genetic DisordersStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Investigators
- Farid Boulad, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00578435
- Sponsor's protocol ID
- 94-005
- Status last verified
- Sep 2008
- First submitted
- 18 Dec 2007
- Last updated
- 12 Sep 2008
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Bone Marrow Transplantation for the Treatment of Genetic Disorders of Erythropoiesis
- ClinicalTrials.gov ID
- NCT00578435
- Acronym / sponsor ID
- 94-005
- Conditions
- Genetic Disorders, Sickle Cell Anemia
- Keywords
- ERYTHROPOIESIS, Genetic Disorders, Sickle Cell Anemia, Thalassemia, Diamond Blackfan Anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- Jan 1994
- Primary completion
- Aug 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 21 Dec 2007 (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 determine and confirm the role of bone marrow transplantation in the treatment of disorders of the red cell and hemoglobin including sickle cell anemia, thalassemia and diamond blackfan anemia.
Detailed description
The trial proposed is a single armed phase II treatment protocol designed to examine the engraftment,toxicity and graft-versus-host disease following a novel cytoreductive regimen including cyclophosphamide and Busulfan for the treatment of patients with Severe Sickle Cell Anemia,Thalassemia, and Diamond Blackfan Anemia using stem cell transplants derived from HLA-genotypically identical siblings.
Patients will be conditioned for transplantation with cyclophosphamide (50 mg/kg/day x 4 days), and busulfan [(if < 4 years of age 1 mg/kg 4 times per day x 4 days), (if > 4 years of age 0.8 mg/kg 4 times per day x 4 days)]. Patients will receive Methotrexate \& Cyclosporin-A for prophylaxis against GvHD and GCSF to promote engraftment.
The preferred source of stem cells from related HLA-matched related donors will be unmodified bone marrow stem cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- Patients with severe HOMOZYGOUS SICKLE CELL ANEMIA or SICKLE/BETA THALASSEMIA
- Neurologic event (stroke or hemorrhage).
- Abnormal cerebral MRI scan and cerebral arteriogram or MRI angiographic study (MRA) and impaired neuropsychologic testing.
- Recurrent acute chest syndrome (> 2 episodes)
- Stage I-II sickle chronic lung disease
Key exclusion criteria (9 listed)
- Patients whose life expectancy is less than 8 weeks. Patients with a Karnofsky or Lansky performance score of < 70%
- Patients with severe major organ dysfunction:
- Patients with severe renal impairment. This will be determined by a creatinine clearance < 70 ml/min/1.73 m2 (or serum creatinine > 1.5 x Normal) or by a glomerular filtration rate < 30% of predicted normal for age
- Inadequate cardiac function as determined by fractional shortening < 28% on echocardiogram, and/or ejection fraction of < 50% on echocardiogram or RNCA.
- Patients with FS of 23-28% who show an increase in FS in response to stress on the supine bicycle ergometer are eligible
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 |
|---|---|---|
| Busulfan, Cyclophosphamide, BMDBusulfan 0.8 or 1 mg/Kg/day Days 8-6 Cyclophosphamide 50 mg/Kg/day Days 2-5 BMT Day 0 | Procedure or surgery | – |
Primary outcome
Define the role of bone marrow transplantation for the treatment of sickle cell disease and the reversibility of sickle cell vasculopathy and organ damage, good risk thalassemia major and Diamond-Blackfan Anemia.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2008.
- Memorial Sloan-Kettering web siteLink 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.
Farid Boulad, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Busulfan, Cyclophosphamide, BMD in people with Genetic Disorders and Sickle Cell Anemia, run by Memorial Sloan Kettering 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 18 inclusion and 9 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 12 Sep 2008. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Define the role of bone marrow transplantation for the treatment of sickle cell disease and the reversibility of sickle cell vasculopathy and organ damage, good risk thalassemia major and Diamond-Blackfan Anemia. (time frame: 2 years). 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 12 Sep 2008.