Fanconi AnemiaPhase 2RAFANCT02143830
HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy
A Phase 2 study testing Busulfan, Cyclophosphamide and Fludarabine in people with Fanconi Anemia and Severe Marrow Failure, run by Children's Hospital Medical Center, Cincinnati at 3 sites in United States.
Trial summary
The purpose of this study is to determine whether the use of lower doses of busulfan and the elimination of cyclosporine will further reduce transplant-related side effects for patients with Fanconi Anemia (FA). Read more about this study
- Who is it for?
- Ages 3 months and older
- Conditions the study is for
- Fanconi Anemia, Severe Marrow Failure, Myelodysplastic Syndrome (MDS)
- What is being tested?
- Busulfan, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 2014to Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 3 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have a diagnosis of Fanconi anemia
- 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
- Hgb <8 gm/dl or red cell transfusion dependence*
Show all 18Show fewer
- Myelodysplastic Syndrome (MDS) (based on WHO or IPSS Classification
- Acute Myelogenous Leukemia (untreated, in remission or with refractory or relapsed disease)
- Donors will be either human leukocyte antigen (HLA) compatible unrelated or HLA-genotypically matched related donors (no fully matched sibling donor).
- Patients and donors may be of either gender or any ethnic background.
- Patients must have a Karnofsky adult, or Lansky pediatric performance scale status > 70%.
- Patients must have adequate physical function measured by:
- Cardiac: asymptomatic or if symptomatic then 1) left ventricular ejection fraction (LVEF) at rest must be > 50% and must improve with exercise or 2) Shortening Fraction > 29%
- Hepatic: < 5 x upper limit of normal (ULN) alanine transaminase (ALT) and < 2.0 mg/dl total serum bilirubin.
- Renal: serum creatinine <1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl > 50 ml/min/1.73 m2
- Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted
- Each patient must be willing to participate as a research subject and must sign an informed consent form.
- 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 leukemia
- Female patients who are pregnant (positive serum or urine HCG) or breast-feeding.
- Active uncontrolled viral, bacterial or fungal infection
- Patient seropositive for HIV-I/II; HTLV -I/II
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 2 recruiting
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Parinda Mehta, MD
- Completed
Memorial Sloan Kettering Cancer Center
New York, New York, 10174
- Recruiting
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Sheri Ballard, 206-667-4222, sballard@fredhutch.org
K. Scott Baker, MD
About this study
Official title: A Phase II Trial of HSCT for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Risk-Adjusted Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
The purpose of this study is to determine whether the use of lower doses of busulfan and the elimination of cyclosporine will further reduce transplant-related side effects for patients with Fanconi Anemia (FA). Patients will undergo a transplant utilizing mis-matched related or matched unrelated donors following a preparative regimen of busulfan, fludarabine, anti-thymocyte globulin and cyclophosphamide.
Read the detailed description
The trial proposed is a three arm phase II treatment protocol designed to investigate the safety and efficacy of risk-adjusted 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. Candidates for this trial will include patients with Fanconi anemia presenting with severe marrow failure (transfusion dependent) or myelodysplastic syndrome, or acute myelogenous leukemia for whom an allogeneic stem cell transplant is indicated.
- Conditions
- Fanconi Anemia, Severe Marrow Failure, Myelodysplastic Syndrome (MDS), Acute Myelogenous Leukemia (AML)
- Being tested
- Busulfan, Cyclophosphamide, Fludarabine, rabbit ATG, G-CSF
- Keywords
- marrow aplasia, cytopenia, myelodysplasia, AML, bone marrow transplant, cytoreductive regimen, T-cell reduction
- Medical subject headings
- Fanconi Anemia, Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Cytopenia, Anemia, Refractory, with Excess of Blasts
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Also called Myleran, Busulfex IV
A standard dose of busulfan, associated with excellent outcomes in our previous trial will be used for young patients with marrow aplasia (arm A).
A higher dose of busulfan will be used in younger patients with MDS and AML (arm B) to maximize disease control.
A lower dose of busulfan will be used in older patients (arm C) to minimize toxicity.
CyclophosphamideDrug
Also called Cytoxan
Arms A, B and C - Cytoxan will be given as a 1-2 hour infusion for 4 days. The dose will be adjusted according to patients ideal body weight for obese patients.
FludarabineDrug
Also called Fludara
Arms A, B and C - Fludarabine will be given IV over 30 minutes daily for 4 days. The dose will be adjusted according to renal function according to Institutional guidelines.
rabbit ATGDrug
Also called thymoglobulin
Arms A, B and C - 4 doses will be given prior to transplant to promote engraftment.
G-CSFDrug
Also called Granulocyte colony-stimulating factor, filgrastim, neupogen
All patients will also receive G-CSF post-transplant to foster engraftment.
Peripheral blood stem cellBiological
The source of stem cells for all patients will be peripheral blood stem cells (PBSC) induced and mobilized by treatment of the donor with G-CSF for 4-6 days. T-cell depletion will be uniformly performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device).
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Good Risk Patients | Experimental | Patients 18 years old or younger with marrow aplasia or single lineage cytopenias will be receive intravenous busulfan (4 doses x 2 days), cyclophosphamide (4 doses x 4 days) and fludarabine (4 doses x 4 days), as used in our most current study that led to > 90% survival rates . Busulfan pharmacokinetics will not be used. All patients will receive rabbit ATG (4 doses x 4 days) prior to and granulocyte-colony stimulating factor (G-CSF) after transplant to promote engraftment. Cyclosporine will not be used for GVHD prophylaxis. The source of the stem cells for all patients will be peripheral blood stem cells mobilized by treatment of the donor with G-CSF. T-cell depletion will be performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device). Enrollment on this arm will include up to 50 patients. Receives: Drug: Busulfan; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: rabbit ATG; Drug: G-CSF; Biological: Peripheral blood stem cell |
| Arm B: Intermediate Risk Patients | Experimental | Patients 18 years old or younger with MDS or AML will receive intravenous busulfan (4 doses x 2 days), cyclophosphamide (4 doses x 4 days) and fludarabine (4 doses x 4 days). Busulfan pharmacokinetics will be used in this arm, as the dose of busulfan is higher. All patients will receive rabbit ATG (thymoglobulin) (4 doses x 4 days) prior to and G-CSF post transplant to promote engraftment. Cyclosporine will not be used for prophylaxis against GVHD. The source of the stem cells for all patients will be peripheral blood stem cells induced and mobilized by treatment of the donor. T-cell will be performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device).
The maximum number of patients enrolled in this arm will be 10. Receives: Drug: Busulfan; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: rabbit ATG; Drug: G-CSF; Biological: Peripheral blood stem cell |
| Arm C: High Risk Patients | Experimental | Patients 19 years old or older with marrow aplasia or MDS or AML will receive intravenous busulfan (4 doses x 2 days), cyclophosphamide (4 doses x 4 days) and fludarabine (4 doses x 4 days). In this study, we will test whether outcomes can be improved, yet engraftment maintained, with a slightly reduced dose of busulfan. Patients will receive rabbit ATG (4 doses x 4 days) prior to and G-CSF post transplant to promote engraftment. Cyclosporine will not be used for GVHD prophylaxis. The source of the stem cells will be peripheral blood stem cells collected from donors treated with G-CSF. T-cell depletion will be performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device). The maximum number of patients enrolled will be 10. Receives: Drug: Busulfan; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: rabbit ATG; Drug: G-CSF; Biological: Peripheral blood stem cell |
What is being measured
The primary outcome is the main question the study is designed to answer.
Graft Failure or Rejection
Primary non-engraftment is diagnosed when the patient fails to achieve an ANC >=500/mm3 at any time in the first 28 days post-transplant. If (1) after achievement of an absolute neutrophil count (ANC) >=500/mm3, the ANC declines to <500/mm3 for more than 3 consecutive days in the absence of relapse, or, (2) there is absence of donor cells in the marrow and/or blood as demonstrated by chimerism assay in the absence of relapse, a diagnosis of secondary graft failure is made. The patient is not evaluable for graft failure or rejection if recurrence of host MDS is detected concurrently.
Measured: 5 years
Secondary outcomes (1)
Post-transplant severe morbidity and mortality
The occurrence of severe post-transplant regimen-related severe morbidity (grade IV toxicity) and/or mortality will be the second endpoint of this study. In the context of the agents or agent-combination used for cytoreduction used, particular attention will be given to toxicity involving (1) the liver, (2) the lungs, (3) the oral mucosa and gastrointestinal tract, and (4) the central nervous system.
Measured: 2 years post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2014 (estimated)
- Study startApr 2014
- Primary completionDec 2026 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fanconi AnemiaStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Parinda Mehta, MD, Principal investigator, CCHMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02143830
- Sponsor's protocol ID
- 2013-7501
- Acronym
- RAFA
- Status last verified
- Nov 2025
- First submitted
- 28 Apr 2014
- Last updated
- 12 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of HSCT for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Risk-Adjusted Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
- ClinicalTrials.gov ID
- NCT02143830
- Acronym / sponsor ID
- RAFA / 2013-7501
- Conditions
- Fanconi Anemia, Severe Marrow Failure, Myelodysplastic Syndrome (MDS), Acute Myelogenous Leukemia (AML)
- Keywords
- marrow aplasia, cytopenia, myelodysplasia, AML, bone marrow transplant, cytoreductive regimen, T-cell reduction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Memorial Sloan Kettering Cancer Center, Fred Hutchinson Cancer Center
- Study start
- Apr 2014
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 21 May 2014 (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 whether the use of lower doses of busulfan and the elimination of cyclosporine will further reduce transplant-related side effects for patients with Fanconi Anemia (FA). Patients will undergo a transplant utilizing mis-matched related or matched unrelated donors following a preparative regimen of busulfan, fludarabine, anti-thymocyte globulin and cyclophosphamide.
Detailed description
The trial proposed is a three arm phase II treatment protocol designed to investigate the safety and efficacy of risk-adjusted 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. Candidates for this trial will include patients with Fanconi anemia presenting with severe marrow failure (transfusion dependent) or myelodysplastic syndrome, or acute myelogenous leukemia for whom an allogeneic stem cell transplant is indicated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: Good Risk Patients | Experimental | Drug: Busulfan, Drug: Cyclophosphamide, Drug: Fludarabine, Drug: rabbit ATG, Drug: G-CSF, Biological: Peripheral blood stem cellPatients 18 years old or younger with marrow aplasia or single lineage cytopenias will be receive intravenous busulfan (4 doses x 2 days), cyclophosphamide (4 doses x 4 days) and fludarabine (4 doses x 4 days), as used in our most current study that led to > 90% survival rates . Busulfan pharmacokinetics will not be used. All patients will receive rabbit ATG (4 doses x 4 days) prior to and granulocyte-colony stimulating factor (G-CSF) after transplant to promote engraftment. Cyclosporine will not be used for GVHD prophylaxis. The source of the stem cells for all patients will be peripheral blood stem cells mobilized by treatment of the donor with G-CSF. T-cell depletion will be performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device). Enrollment on this arm will include up to 50 patients. |
| Arm B: Intermediate Risk Patients | Experimental | Drug: Busulfan, Drug: Cyclophosphamide, Drug: Fludarabine, Drug: rabbit ATG, Drug: G-CSF, Biological: Peripheral blood stem cellPatients 18 years old or younger with MDS or AML will receive intravenous busulfan (4 doses x 2 days), cyclophosphamide (4 doses x 4 days) and fludarabine (4 doses x 4 days). Busulfan pharmacokinetics will be used in this arm, as the dose of busulfan is higher. All patients will receive rabbit ATG (thymoglobulin) (4 doses x 4 days) prior to and G-CSF post transplant to promote engraftment. Cyclosporine will not be used for prophylaxis against GVHD. The source of the stem cells for all patients will be peripheral blood stem cells induced and mobilized by treatment of the donor. T-cell will be performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device). The maximum number of patients enrolled in this arm will be 10. |
| Arm C: High Risk Patients | Experimental | Drug: Busulfan, Drug: Cyclophosphamide, Drug: Fludarabine, Drug: rabbit ATG, Drug: G-CSF, Biological: Peripheral blood stem cellPatients 19 years old or older with marrow aplasia or MDS or AML will receive intravenous busulfan (4 doses x 2 days), cyclophosphamide (4 doses x 4 days) and fludarabine (4 doses x 4 days). In this study, we will test whether outcomes can be improved, yet engraftment maintained, with a slightly reduced dose of busulfan. Patients will receive rabbit ATG (4 doses x 4 days) prior to and G-CSF post transplant to promote engraftment. Cyclosporine will not be used for GVHD prophylaxis. The source of the stem cells will be peripheral blood stem cells collected from donors treated with G-CSF. T-cell depletion will be performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device). The maximum number of patients enrolled will be 10. |
Who may qualify
- Ages
- 3 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have a diagnosis of Fanconi anemia
- Patients must have one of the following hematologic diagnoses:
- Donors will be either human leukocyte antigen (HLA) compatible unrelated or HLA-genotypically matched related donors (no fully matched sibling donor).
- Patients and donors may be of either gender or any ethnic background.
- Patients must have a Karnofsky adult, or Lansky pediatric performance scale status > 70%.
Key exclusion criteria (4 listed)
- Active CNS leukemia
- Female patients who are pregnant (positive serum or urine HCG) or breast-feeding.
- 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 |
|---|---|---|
| BusulfanAlso: Myleran, Busulfex IVA standard dose of busulfan, associated with excellent outcomes in our previous trial will be used for young patients with marrow aplasia (arm A). A higher dose of busulfan will be used in younger patients with MDS and AML (arm B) to maximize disease control. A lower dose of busulfan will be used in older patients (arm C) to minimize toxicity. | Drug | Arm A: Good Risk Patients, Arm B: Intermediate Risk Patients, Arm C: High Risk Patients |
| CyclophosphamideAlso: CytoxanArms A, B and C - Cytoxan will be given as a 1-2 hour infusion for 4 days. The dose will be adjusted according to patients ideal body weight for obese patients. | Drug | Arm A: Good Risk Patients, Arm B: Intermediate Risk Patients, Arm C: High Risk Patients |
| FludarabineAlso: FludaraArms A, B and C - Fludarabine will be given IV over 30 minutes daily for 4 days. The dose will be adjusted according to renal function according to Institutional guidelines. | Drug | Arm A: Good Risk Patients, Arm B: Intermediate Risk Patients, Arm C: High Risk Patients |
| rabbit ATGAlso: thymoglobulinArms A, B and C - 4 doses will be given prior to transplant to promote engraftment. | Drug | Arm A: Good Risk Patients, Arm B: Intermediate Risk Patients, Arm C: High Risk Patients |
| G-CSFAlso: Granulocyte colony-stimulating factor, filgrastim, neupogenAll patients will also receive G-CSF post-transplant to foster engraftment. | Drug | Arm A: Good Risk Patients, Arm B: Intermediate Risk Patients, Arm C: High Risk Patients |
| Peripheral blood stem cellThe source of stem cells for all patients will be peripheral blood stem cells (PBSC) induced and mobilized by treatment of the donor with G-CSF for 4-6 days. T-cell depletion will be uniformly performed by positive CD34 selection with the use of the Miltenyi system (CliniMACS device). | Biological | Arm A: Good Risk Patients, Arm B: Intermediate Risk Patients, Arm C: High Risk Patients |
Primary outcome
Graft Failure or Rejection
Time frame: 5 years
Primary non-engraftment is diagnosed when the patient fails to achieve an ANC >=500/mm3 at any time in the first 28 days post-transplant. If (1) after achievement of an absolute neutrophil count (ANC) >=500/mm3, the ANC declines to <500/mm3 for more than 3 consecutive days in the absence of relapse, or, (2) there is absence of donor cells in the marrow and/or blood as demonstrated by chimerism assay in the absence of relapse, a diagnosis of secondary graft failure is made. The patient is not evaluable for graft failure or rejection if recurrence of host MDS is detected concurrently.
1 secondary outcome
Post-transplant severe morbidity and mortality
Time frame: 2 years post-transplant
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2025.
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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.
Parinda Mehta, MD principal investigator
CCHMC
3 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, Cyclophosphamide and Fludarabine in people with Fanconi Anemia and Severe Marrow Failure, run by Children's Hospital Medical Center, Cincinnati at 3 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 18 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: looking for participants now, as of the sponsor's last update on 12 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jamie Wilhelm ((513)803-1102, Jamie.Wilhelm@cchmc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Graft Failure or Rejection (time frame: 5 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 Nov 2025.