Aplastic AnemiaPhase 2NCT00987480
Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
A Phase 2 study testing Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine. and CliniMACS device in people with Aplastic Anemia and Leukemia, run by Memorial Sloan Kettering Cancer Center at 6 sites in United States.
Trial summary
This is a genetic disease (transmitted through the parents' genes) called Fanconi Anemia. Because of that genetic disease, the bone marrow has changed and now has failed, or has given rise to a preleukemia called myelodysplastic syndrome (MDS) or leukemia (acute myelogenous leukemia or AML). Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Aplastic Anemia, Leukemia, Myelodysplastic Syndrome
- What is being tested?
- Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine. and CliniMACS device
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 6 sitesUnited States
- Study dates
- 25 Sep 2009to 10 Jul 2017
- Phase
- Phase 2
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Patients must have a diagnosis of Fanconi anemia (confirmed by mitomycin C or diepoxybutane [DEB] chromosomal breakage testing at an approved laboratory).
- Hematologic Diagnosis and Status - Patients must have one of the following hematologic diagnoses:
- Severe Aplastic Anemia (SAA) with bone marrow cellularity of <25%, or Severe Isolated Single lineage Cytopenia
- AND at least one of the following features:
- Platelet count <20 x 109/L or platelet transfusion dependence*
- ANC <1000 x 109/L
Show all 37Show fewer
- Hgb <8 gm/dl or red cell transfusion dependence*
- Myelodysplastic Syndrome (MDS) (Appendix 1: MDS Classification) - MDS at any stage, based on either one of the following classifications:
- WHO Classification
- Refractory anemia and transfusion dependence*
- Any of other stages
- IPSS Classification
- Low risk (score 0) and transfusion dependence*
- Any other risk groups Score > or = to 0.5
- Acute Myelogenous Leukemia
- Patients with acute leukemia are included in this trial in remission, refractory or relapsed disease.
- Transfusion dependence will be defined as greater than ONE transfusion of platelets or red blood cells in the last year prior to evaluation on protocol.
- Donors:
- Donor choices will be determined by the investigators at each of the centers according to their own institutional criteria.
- All patients evaluated at trial sites and eligible for this trial by virtue of disease and lack of an HLA-genotypically matched related donor will be captured in the database of this trial. Patients who will be enrolled on this protocol must have one of the following donor choices:
- HLA-compatible Unrelated volunteer donors
- Patients who do not have a related HLA-matched donor but have an unrelated donor who is either matched at all A, B, C and DRB1 (8/8) loci or who is mismatched at 1/8 loci (A, B, C or DRB1) (7/8) as tested by DNA analysis (high resolution), will be eligible for entry on this protocol.
- HLA-mismatched Related donors
- Patients who do not have a related or unrelated HLA-compatible donor must have a healthy family member who is at least HLA-haplotype identical to the recipient. First degree related donors must have a normal DEB test.
- The donor must be healthy and willing and able to receive a 4-6 day course of G-CSF and undergo 1-3 daily leukaphereses.
- Related and Unrelated donors must be medically evaluated and fulfill the criteria for collection of PBSCs as per institutional guidelines.
- Patients:
- Patients and donors may be of either gender or any ethnic background.
- Patients must have a Karnofsky adult, or Lansky pediatric performance scale status > or = 70%.
- At the time of referral for transplantation, patients must have no co-existing medical problems that would significantly increase the risk of the transplant procedure.
- Patients must have adequate physical function measured by :
- Cardiac: asymptomatic or if symptomatic then 1) LVEF at rest must be > or = to 50% and must improve with exercise or 2) Shortening Fraction > or = to 29%
- Hepatic: < 5 x ULN SGOT and < 2.0 mg/dl total serum bilirubin.
- Renal: serum creatinine < or = to 1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl > 60-ml/min/1.73 m2
- Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)
- Each patient must be willing to participate as a research subject and must sign an informed consent form. Parent or legal guardians of patients who are minors will sign the informed consent form. Assents will be obtained as age appropriate.
- Female patients and donors must not be pregnant or breastfeeding at the time of signing consent. Women must be willing to undergo a pregnancy test prior to transplant and avoid becoming pregnant while on study.
Who cannot join
- Active CNS leukemic involvement
- Female patients who are pregnant (positive serum or urine HCG) or breast-feeding. Women of childbearing age must avoid becoming pregnant while on study.
- Active uncontrolled viral, bacterial or fungal infection
- Patient seropositive for HIV-I/II; HTLV -I/II
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Children's Hospital Boston
Boston, Massachusetts, 02115
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Children's Hospital of Wisconsin
Milwaukee, Wisconsin
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
The Rockefeller University
New York, New York, 10065
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
About this study
Official title: A Multicenter Phase II Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
This is a genetic disease (transmitted through the parents' genes) called Fanconi Anemia. Because of that genetic disease, the bone marrow has changed and now has failed, or has given rise to a preleukemia called myelodysplastic syndrome (MDS) or leukemia (acute myelogenous leukemia or AML).
Without treatment these complications of Fanconia anemia (FA) are fatal. The only treatment that can cure these complications is an allogeneic transplant of stem cells, meaning, giving the patient bone marrow cells from a healthy donor that can produce normal blood cells that will replace the bone marrow that is sick.
Read more
What has been given for the treatment of FA in the past is to use a combination of low doses of radiation to the whole body (total body irradiation) and low doses of the chemotherapy drugs (cyclophosphamide and fludarabine) before the transplant. However, the use of radiation can, later on, increase the chances of getting a second cancer of the skin, head or the neck. These chances of a second cancer are higher than normal in patients with FA.
The purpose of this study is to find out if the doctors can do the same thing with the same chemotherapy drugs used in the past. However physicians will use another chemotherapy drug called busulfan instead of the radiation. The goal of this study is to get rid of the short term and long term risks of the radiation. The first new part of this treatment will be to replace drugs for radiation with chemotherapy drugs.
- Conditions
- Aplastic Anemia, Leukemia, Myelodysplastic Syndrome
- Being tested
- Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine., CliniMACS device
- Keywords
- Stem Cell Transplantation, Anemia, Busulfan, Cyclophosphamide, Fludarabine, 08-031
- Medical subject headings
- Anemia, Aplastic, Leukemia, Myelodysplastic Syndromes, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.Drug
There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year.
CliniMACS deviceDevice
CD34+ T-cell depleted peripheral blood stem cell transplant
| Study group | Role | What they receive |
|---|---|---|
| chemotherapy-based cytoreductive regimen plus a CD34+ selected | Experimental | This phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. Receives: Drug: Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.; Device: CliniMACS device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Successful Neutrophil Engraftment
Measured: 2 years
The Incidence of Early Transplant Related Mortality
Measured: 2 years
The Incidence of Acute GvHD
Measured: 100 days
The Incidence of Chronic GvHD
Measured: 2 years
Secondary outcomes (2)
Overall Survival at 3 Years
Overall Survival is defined as time from date of transplant to event (death from any cause) or last follow-up.
Measured: 3 years
Disease-free Survival at 3 Years
Defined as time from date of transplant to relapse, graft rejection or graft failure, or death.
Primary non-engraftment is diagnosed when the participants fails to achieve an ANC >/= 500/ul at any time in the first 28 days post-transplant.
For participants with MDS or AML, relapse will be analyzed as to type and genetic origin of the MDS/leukemic cells. These will be defined by an increasing number of blasts in the marrow over 5% by the presence of circulating peripheral blasts, or by the presence of blasts in any extramedullary site. Cytogenetic analysis of the marrow and/or peripheral blood will also be obtained for the diagnosis of relapse.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2009 (estimated)
- Study start25 Sep 2009
- Primary completion10 Jul 2017
- Study completion10 Jul 2017
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Aplastic AnemiaStudies 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
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Boston Children's Hospital, Children's Hospital Medical Center, Cincinnati, Children's Hospital and Health System Foundation, Wisconsin, Rockefeller University, Fred Hutchinson Cancer Center
- Responsible party
- Sponsor
- Investigators
- Faird Boulad, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00987480
- Sponsor's protocol ID
- 08-031
- Status last verified
- Jun 2018
- First submitted
- 30 Sep 2009
- Last updated
- 10 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
van Hoogdalem MW, Emoto C, Fukuda T, Mizuno T, Mehta PA, Vinks AA. Population pharmacokinetic modelling of busulfan and the influence of body composition in paediatric Fanconi anaemia patients. Br J Clin Pharmacol. 2020 May;86(5):933-943. doi: 10.1111/bcp.14202. Epub 2020 Jan 23.
PubMed 31851762Mehta PA, Davies SM, Leemhuis T, Myers K, Kernan NA, Prockop SE, Scaradavou A, O'Reilly RJ, Williams DA, Lehmann L, Guinan E, Margolis D, Baker KS, Lane A, Boulad F. Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study. Blood. 2017 Apr 20;129(16):2308-2315. doi: 10.1182/blood-2016-09-743112. Epub 2017 Feb 8.
PubMed 28179273
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase II Trial of Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
- ClinicalTrials.gov ID
- NCT00987480
- Acronym / sponsor ID
- 08-031
- Conditions
- Aplastic Anemia, Leukemia, Myelodysplastic Syndrome
- Keywords
- Stem Cell Transplantation, Anemia, Busulfan, Cyclophosphamide, Fludarabine, 08-031
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Boston Children's Hospital, Children's Hospital Medical Center, Cincinnati, Children's Hospital and Health System Foundation, Wisconsin, Rockefeller University, Fred Hutchinson Cancer Center
- Study start
- 25 Sep 2009 (actual)
- Primary completion
- 10 Jul 2017 (actual)
- Study completion
- 10 Jul 2017 (actual)
- First posted
- 1 Oct 2009 (estimated)
- Results
- Posted 10 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a genetic disease (transmitted through the parents' genes) called Fanconi Anemia. Because of that genetic disease, the bone marrow has changed and now has failed, or has given rise to a preleukemia called myelodysplastic syndrome (MDS) or leukemia (acute myelogenous leukemia or AML).
Without treatment these complications of Fanconia anemia (FA) are fatal. The only treatment that can cure these complications is an allogeneic transplant of stem cells, meaning, giving the patient bone marrow cells from a healthy donor that can produce normal blood cells that will replace the bone marrow that is sick.
What has been given for the treatment of FA in the past is to use a combination of low doses of radiation to the whole body (total body irradiation) and low doses of the chemotherapy drugs (cyclophosphamide and fludarabine) before the transplant. However, the use of radiation can, later on, increase the chances of getting a second cancer of the skin, head or the neck. These chances of a second cancer are higher than normal in patients with FA.
The purpose of this study is to find out if the doctors can do the same thing with the same chemotherapy drugs used in the past. However physicians will use another chemotherapy drug called busulfan instead of the radiation. The goal of this study is to get rid of the short term and long term risks of the radiation. The first new part of this treatment will be to replace drugs for radiation with chemotherapy drugs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| chemotherapy-based cytoreductive regimen plus a CD34+ selected | Experimental | Drug: Busulfan, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine., Device: CliniMACS deviceThis phase II trial is designed to investigate the safety and efficacy of a chemotherapy-based cytoreductive regimen plus a CD34+ selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the treatment of patients with Fanconi anemia and severe hematologic disease. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (37 listed)
- Patients must have a diagnosis of Fanconi anemia (confirmed by mitomycin C or diepoxybutane [DEB] chromosomal breakage testing at an approved laboratory).
- Hematologic Diagnosis and Status - Patients must have one of the following hematologic diagnoses:
- Platelet count <20 x 109/L or platelet transfusion dependence*
- ANC <1000 x 109/L
- Hgb <8 gm/dl or red cell transfusion dependence*
Key exclusion criteria (4 listed)
- Active CNS leukemic involvement
- Female patients who are pregnant (positive serum or urine HCG) or breast-feeding. Women of childbearing age must avoid becoming pregnant while on study.
- Active uncontrolled viral, bacterial or fungal infection
- Patient seropositive for HIV-I/II; HTLV -I/II
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, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine.There are three parts in this transplant study. 1) There will be a pre-transplant - preparation - period to see if patient qualifies for the transplant study. This will be done as an outpatient and lasts 2-4 weeks. Once this is completed, there will be 2) the transplant period itself, during which the patient will be admitted and will be an inpatient. This period usually last for 4-6 weeks. Following that, there will be a 3) post transplant period, during which the patient will be watched carefully and monitored in clinic as an out patient. The post transplant period lasts from three months to one year. | Drug | chemotherapy-based cytoreductive regimen plus a CD34+ selected |
| CliniMACS deviceCD34+ T-cell depleted peripheral blood stem cell transplant | Device | chemotherapy-based cytoreductive regimen plus a CD34+ selected |
Primary outcome
Successful Neutrophil Engraftment
Time frame: 2 years
The Incidence of Early Transplant Related Mortality
Time frame: 2 years
The Incidence of Acute GvHD
Time frame: 100 days
The Incidence of Chronic GvHD
Time frame: 2 years
2 secondary outcomes
Overall Survival at 3 Years
Time frame: 3 years
Disease-free Survival at 3 Years
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31851762van Hoogdalem MW, Emoto C, Fukuda T, Mizuno T, Mehta PA, Vinks AA. Population pharmacokinetic modelling of busulfan and the influence of body composition in paediatric Fanconi anaemia patients. Br J Clin Pharmacol. 2020 May;86(5):933-943. doi: 10.1111/bcp.14202. Epub 2020 Jan 23.
- Derived from this study: PubMed 28179273Mehta PA, Davies SM, Leemhuis T, Myers K, Kernan NA, Prockop SE, Scaradavou A, O'Reilly RJ, Williams DA, Lehmann L, Guinan E, Margolis D, Baker KS, Lane A, Boulad F. Radiation-free, alternative-donor HCT for Fanconi anemia patients: results from a prospective multi-institutional study. Blood. 2017 Apr 20;129(16):2308-2315. doi: 10.1182/blood-2016-09-743112. Epub 2017 Feb 8.
- Memorial Sloan-Kettering 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.
Faird Boulad, MD principal investigator
Memorial Sloan Kettering Cancer Center
6 sites 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, fludarabine, & cyclophosphamide with immunosuppression with ATG and cyclosporine. and CliniMACS device in people with Aplastic Anemia and Leukemia, run by Memorial Sloan Kettering Cancer Center at 6 sites 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 37 inclusion and 4 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 10 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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?
Yes. Results are posted in the registry (first posted 10 Jul 2018). 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?
Successful Neutrophil Engraftment (time frame: 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00987480, which also lists 2 linked publications.
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 10 Jul 2018.