HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy

NCT ID: NCT02143830

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-30

Study Completion Date

2028-12-31

Brief Summary

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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

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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

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Fanconi Anemia Severe Marrow Failure Myelodysplastic Syndrome (MDS) Acute Myelogenous Leukemia (AML)

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Busulfan

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

G-CSF

Intervention Type DRUG

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

Peripheral blood stem cell

Intervention Type BIOLOGICAL

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).

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.

Group Type EXPERIMENTAL

Busulfan

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

G-CSF

Intervention Type DRUG

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

Peripheral blood stem cell

Intervention Type BIOLOGICAL

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).

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.

Group Type EXPERIMENTAL

Busulfan

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

G-CSF

Intervention Type DRUG

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

Peripheral blood stem cell

Intervention Type BIOLOGICAL

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).

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

rabbit ATG

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

Intervention Type DRUG

G-CSF

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

Intervention Type DRUG

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).

Intervention Type BIOLOGICAL

Other Intervention Names

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Myleran Busulfex IV Cytoxan Fludara thymoglobulin Granulocyte colony-stimulating factor filgrastim neupogen

Eligibility Criteria

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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
Minimum Eligible Age

3 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Parinda Mehta, MD

Role: PRINCIPAL_INVESTIGATOR

CCHMC

Locations

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Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status COMPLETED

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Jamie Wilhelm

Role: CONTACT

Phone: (513)803-1102

Email: [email protected]

Sara Loveless, RN

Role: CONTACT

Phone: (513)803-7656

Email: [email protected]

Facility Contacts

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Sheri Ballard

Role: primary

Other Identifiers

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2013-7501

Identifier Type: -

Identifier Source: org_study_id