Recruiting
Phase 2

HSCT with Chemotherapy

Sponsor:

Children's Hospital Medical Center, Cincinnati

Code:

NCT02143830

Conditions

Fanconi Anemia

Severe Marrow Failure

Myelodysplastic Syndrome (MDS)

Acute Myelogenous Leukemia (AML)

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

Busulfan

Cyclophosphamide

Fludarabine

rabbit ATG

G-CSF

Study Details

Brief 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). 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.

Conditions

Fanconi Anemia

Severe Marrow Failure

Myelodysplastic Syndrome (MDS)

Acute Myelogenous Leukemia (AML)

Study ID

NCT02143830

Start date

Apr, 2014

Status verified date

Nov, 2025

Completion date

Dec, 2028

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patients must have a diagnosis of Fanconi anemia
  • Patients must have one of the following hematologic diagnoses:

1. Severe Aplastic Anemia (SAA), with bone marrow cellularity of <25% OR Severe Isolated Single Lineage Cytopenia and at least one of the following features:

1. Platelet count <20 x 109/L or platelet transfusion dependence\*
2. ANC <1000 x 109/L
3. Hgb <8 gm/dl or red cell transfusion dependence\*
2. Myelodysplastic Syndrome (MDS) (based on WHO or IPSS Classification
3. 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:

1. 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%
2. Hepatic: < 5 x upper limit of normal (ULN) alanine transaminase (ALT) and < 2.0 mg/dl total serum bilirubin.
3. Renal: serum creatinine <1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl > 50 ml/min/1.73 m2
4. 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.

Exclusion Criteria:

  • 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

Study Design

Enrollment

70 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A: Good Risk Patients

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.

experimental: Arm B: Intermediate Risk Patients

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.

experimental: Arm C: High Risk Patients

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.

Interventions

Busulfan

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.

Cyclophosphamide

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.

Fludarabine

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 ATG

Arms A, B and C - 4 doses will be given prior to transplant to promote engraftment.

G-CSF

All patients will also receive G-CSF post-transplant to foster engraftment.

Peripheral blood stem cell

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).

Primary outcome measure

  • Graft Failure or Rejection [ Time Frame: 5 years ]

Central Contacts and Locations

Central contacts

Jamie Wilhelm

(513)803-1102Jamie.Wilhelm@cchmc.org

Sara Loveless, RN

(513)803-7656Sara.Loveless@cchmc.org

Locations

Cincinnati Children's Hospital Medical Center

Recruiting

Cincinnati, Ohio, United States, 45229

Principal Investigator:

Parinda Mehta, MD

Fred Hutchinson Cancer Research Center

Recruiting

Seattle, Washington, United States, 98109

Contacts

Sheri Ballard

206-667-4222sballard@fredhutch.org

Principal Investigator:

K. Scott Baker, MD

More Information

Sponsor

Children's Hospital Medical Center, Cincinnati

Last update posted

Nov 12, 2025

Last verified

Nov, 2025

Keywords

  • marrow aplasia
  • cytopenia
  • myelodysplasia
  • AML
  • bone marrow transplant
  • cytoreductive regimen
  • T-cell reduction

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Children's Hospital Medical Center, Cincinnati on 2025-11-12.