Congenital Amegakaryocytic ThrombocytopeniaPhase 1/2NCT00305708
Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission
A Phase 1/2 study testing anti-thymocyte globulin, busulfan and fludarabine phosphate in people with Congenital Amegakaryocytic Thrombocytopenia and Diamond-blackfan Anemia, run by University of California, San Francisco at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as busulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Congenital Amegakaryocytic Thrombocytopenia, Diamond-blackfan Anemia, Fanconi Anemia
- What is being tested?
- anti-thymocyte globulin, busulfan and fludarabine phosphate
- Type of treatment
- Surgery or procedure
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2000to Jul 2004
- Phase
- Phase 1/2
- 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 Up to 17 years
- All sexes
- No healthy volunteers
- Child
DISEASE CHARACTERISTICS:
- Diagnosis of one of the following hematopoietic disorders:
- Severe aplastic anemia with marrow aplasia (i.e., absolute neutrophil count < 500/mm^3, platelet and/or red blood cell transfusion dependent), meeting 1 of the following criteria:
- Closely matched related donor
- Unresponsive to immunosuppressive therapy within 3 months after follow-up AND alternative matched unrelated donor available
- Congenital marrow failure syndrome, including any of the following:
- Primary red blood cell aplasia (Diamond-Blackfan syndrome)
- Congenital neutropenia (Kostmann's syndrome)
- Amegakaryocytic thrombocytopenia
- Hemoglobinopathy including any of the following:
- β-thalassemia major
- Sickle cell anemia
- Severe immunodeficiency disease including any of the following:
- Chediak-Higashi disease
- Wiskott-Aldrich syndrome
- Combined immunodeficiency disease (Nezelof's)
- Hyperimmunoglobulin M syndrome
- Bare lymphocyte syndrome
- Other stem cell defects (e.g., osteopetrosis)
- Chronic myelogenous leukemia in first chronic phase
- Not eligible for other ongoing phase II/III studies
- Acute myeloid leukemia in first remission
- Not eligible for other ongoing phase II/III studies
- Inborn errors of metabolism
- No severe combined immunodeficiency disorder
- Available donor, meeting 1 of the following criteria:
- Related donor matched by high resolution DNA typing at both HLA Drβ1 alleles and ≤ 1 mismatch at the 4 HLA-A and -B alleles
- Unrelated donor, meeting one of the following criteria:
- Bone marrow matched by high resolution DNA typing at both HLA Drβ1 alleles and ≤ 1 mismatch by high resolution DNA typing at the 4 HLA-A and -B alleles
- Umbilical cord blood matched at 4/6 HLA-A, -B, and Drβ1 alleles by high resolution typing with ≥ 1 Drβ1 match and ≥ 3 X 10^7 cells/kg body weight of recipient
PATIENT CHARACTERISTICS:
- See Disease Characteristics
- No active bacterial, viral, or fungal infection
- Cardiac shortening fraction ≥ 27%
- Creatinine clearance ≥ 60 mL/min
- DLCO ≥ 60% of predicted (corrected for anemia/lung volume)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSF Comprehensive Cancer Center
San Francisco, California, 94115
About this study
Official title: Bone Marrow Stem Cell Transplantation for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myeloid Leukemia in 1Remission
RATIONALE: Drugs used in chemotherapy, such as busulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. A donor peripheral blood, bone marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin before the transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of busulfan, antithymocyte globulin, and fludarabine when given together with a donor stem cell transplant in treating young patients with blood disorders, bone marrow disorders, chronic myelogenous leukemia in first chronic phase, or acute myeloid leukemia in first remission.
Read the detailed description
OBJECTIVES:
Primary
- Determine the efficacy, in terms of graft rejection at 4 weeks, of a conditioning regimen comprising busulfan, anti-thymocyte globulin, and fludarabine followed by donor stem cell transplantation (SCT) in children with stem cell defects, marrow failure syndromes, chronic myelogenous leukemia in first chronic phase, or acute myeloid leukemia in first remission.
- Determine the pharmacokinetics of busulfan in children undergoing donor SCT.
Secondary
- Determine the toxicity of this regimen in these patients.
- Determine engraftment at 3, 6, 9, and 12 months and mixed chimerism in patients treated with this regimen.
- Determine overall and disease-free survival of patients treated with this regimen.
OUTLINE: Patients receive one of the following cytoreductive regimens:
- Regimen 1 (patients with an HLA genotypic matched sibling donor): Patients receive busulfan IV over 2 hours every 6 hours on days -9 to -6, fludarabine IV on days -5 to -2, and anti-thymocyte globulin (ATG) IV over 10 hours on days -3 to -1.
- Regimen 2 (patients with an HLA closely matched related [not genotypic] or unrelated donor): Patients receive busulfan and fludarabine as in regimen 1, and ATG IV over 10 hours on days -4 to -1.
- Regimen 3 (patients with Fanconi's anemia or severe aplastic anemia with genotypic matched sibling donor): Patients receive fludarabine as in regimen 1 and ATG as in regimen 2.
- Regimen 4 (patients with Fanconi's anemia who have a closely matched related [not genotypic] or unrelated donor): Patients undergo thoracoabdominal irradiation on day -6 and receive fludarabine as in regimen 1 and ATG as in regimen 2.
All patients undergo allogeneic bone marrow, umbilical cord blood, or peripheral blood stem cell transplantation on day 0.
After the completion of study treatment, patients are followed periodically for 20 years.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
- Conditions
- Congenital Amegakaryocytic Thrombocytopenia, Diamond-blackfan Anemia, Fanconi Anemia, Leukemia, Severe Congenital Neutropenia, Thrombocytopenia
- Being tested
- anti-thymocyte globulin, busulfan, fludarabine phosphate, allogeneic bone marrow transplantation, peripheral blood stem cell transplantation
- Keywords
- thrombocytopenia, childhood acute myeloid leukemia in remission, childhood chronic myelogenous leukemia, Diamond-Blackfan anemia, congenital amegakaryocytic thrombocytopenia, Fanconi anemia, severe congenital neutropenia, chronic phase chronic myelogenous leukemia
- Medical subject headings
- Congenital amegakaryocytic thrombocytopenia, Anemia, Diamond-Blackfan, Fanconi Anemia, Leukemia, Neutropenia, Severe Congenital, Autosomal Recessive 3, Thrombocytopenia, Leukemia, Myeloid, Chronic-Phase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
busulfanDrug
allogeneic bone marrow transplantationProcedure or surgery
peripheral blood stem cell transplantationProcedure or surgery
umbilical cord blood transplantationProcedure or surgery
radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Graft rejection measured by ANC < 500 with no evidence of donor cells in blood or marrow from transplantation to week 4 post transplantation
Secondary outcomes (5)
Toxicity grades 3 or 4 assessed from conditioning through 1 year post transplantation
Engraftment at 1, 3, 6, 9, and 12 months post transplantation
Mixed chimerism at 1, 3, 6, 9, and 12 months post transplantation
Survival measured from the day of first dose of conditioning
Disease-free survival measured from the day of first dose of conditioning
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2006 (estimated)
- Study startAug 2000
- Primary completionJul 2004
- Study completionJul 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Amegakaryocytic ThrombocytopeniaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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 1/2
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Morton Cowan, University of California, San Francisco
- Investigators
- Morton J. Cowan, MD, Study chair, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00305708
- Sponsor's protocol ID
- CDR0000462443
- Other IDs
- UCSF-01152, UCSF-H411-17802-06
- Status last verified
- Nov 2012
- First submitted
- 21 Mar 2006
- Last updated
- 12 Nov 2012
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bone Marrow Stem Cell Transplantation for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myeloid Leukemia in 1Remission
- ClinicalTrials.gov ID
- NCT00305708
- Acronym / sponsor ID
- CDR0000462443
- Conditions
- Congenital Amegakaryocytic Thrombocytopenia, Diamond-blackfan Anemia, Fanconi Anemia, Leukemia, Severe Congenital Neutropenia, Thrombocytopenia
- Keywords
- thrombocytopenia, childhood acute myeloid leukemia in remission, childhood chronic myelogenous leukemia, Diamond-Blackfan anemia, congenital amegakaryocytic thrombocytopenia, Fanconi anemia, severe congenital neutropenia, chronic phase chronic myelogenous leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Aug 2000
- Primary completion
- Jul 2004 (actual)
- Study completion
- Jul 2004 (actual)
- First posted
- 22 Mar 2006 (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.
RATIONALE: Drugs used in chemotherapy, such as busulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. A donor peripheral blood, bone marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin before the transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of busulfan, antithymocyte globulin, and fludarabine when given together with a donor stem cell transplant in treating young patients with blood disorders, bone marrow disorders, chronic myelogenous leukemia in first chronic phase, or acute myeloid leukemia in first remission.
Detailed description
OBJECTIVES:
Primary
- Determine the efficacy, in terms of graft rejection at 4 weeks, of a conditioning regimen comprising busulfan, anti-thymocyte globulin, and fludarabine followed by donor stem cell transplantation (SCT) in children with stem cell defects, marrow failure syndromes, chronic myelogenous leukemia in first chronic phase, or acute myeloid leukemia in first remission.
- Determine the pharmacokinetics of busulfan in children undergoing donor SCT.
Secondary
- Determine the toxicity of this regimen in these patients.
- Determine engraftment at 3, 6, 9, and 12 months and mixed chimerism in patients treated with this regimen.
- Determine overall and disease-free survival of patients treated with this regimen.
OUTLINE: Patients receive one of the following cytoreductive regimens:
- Regimen 1 (patients with an HLA genotypic matched sibling donor): Patients receive busulfan IV over 2 hours every 6 hours on days -9 to -6, fludarabine IV on days -5 to -2, and anti-thymocyte globulin (ATG) IV over 10 hours on days -3 to -1.
- Regimen 2 (patients with an HLA closely matched related [not genotypic] or unrelated donor): Patients receive busulfan and fludarabine as in regimen 1, and ATG IV over 10 hours on days -4 to -1.
- Regimen 3 (patients with Fanconi's anemia or severe aplastic anemia with genotypic matched sibling donor): Patients receive fludarabine as in regimen 1 and ATG as in regimen 2.
- Regimen 4 (patients with Fanconi's anemia who have a closely matched related [not genotypic] or unrelated donor): Patients undergo thoracoabdominal irradiation on day -6 and receive fludarabine as in regimen 1 and ATG as in regimen 2.
All patients undergo allogeneic bone marrow, umbilical cord blood, or peripheral blood stem cell transplantation on day 0.
After the completion of study treatment, patients are followed periodically for 20 years.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
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 |
|---|---|---|
| anti-thymocyte globulin | Biological | – |
| busulfan | Drug | – |
| fludarabine phosphate | Drug | – |
| allogeneic bone marrow transplantation | Procedure or surgery | – |
| peripheral blood stem cell transplantation | Procedure or surgery | – |
| umbilical cord blood transplantation | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
Graft rejection measured by ANC < 500 with no evidence of donor cells in blood or marrow from transplantation to week 4 post transplantation
5 secondary outcomes
Toxicity grades 3 or 4 assessed from conditioning through 1 year post transplantation
Engraftment at 1, 3, 6, 9, and 12 months post transplantation
Mixed chimerism at 1, 3, 6, 9, and 12 months post transplantation
Survival measured from the day of first dose of conditioning
Disease-free survival measured from the day of first dose of conditioning
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 Nov 2012.
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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.
Morton J. Cowan, MD study chair
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing anti-thymocyte globulin, busulfan and fludarabine phosphate in people with Congenital Amegakaryocytic Thrombocytopenia and Diamond-blackfan Anemia, run by University of California, San Francisco 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?
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 Nov 2012. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Graft rejection measured by ANC < 500 with no evidence of donor cells in blood or marrow from transplantation to week 4 post transplantation. 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 Nov 2012.