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Alkylating agents

Chemotherapy + Stem Cell Transplant for Fanconi Anemia (RAFA Trial)

Phase 2

Recruiting

Led By Parinda Mehta, MD

Research Sponsored by Children's Hospital Medical Center, Cincinnati

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have a diagnosis of Fanconi anemia

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

Must not have

Active uncontrolled viral, bacterial or fungal infection

Active CNS leukemia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new, less intense chemotherapy treatment for people with Fanconi Anemia who are getting a stem cell transplant from a related or unrelated donor.

Who is the study for?

This trial is for patients with Fanconi Anemia who need a stem cell transplant. They should have specific blood conditions like severe aplastic anemia or leukemia, and be in good physical shape with a performance status over 70%. Pregnant or breastfeeding women can't join, nor can those with HIV, active CNS leukemia, or uncontrolled infections.

What is being tested?

The study tests if lower doses of busulfan without cyclosporine reduce side effects in FA patients getting transplants from mismatched related or unrelated donors. The regimen includes busulfan, fludarabine, anti-thymocyte globulin (ATG), and cyclophosphamide.

What are the potential side effects?

Possible side effects include lowered immunity leading to infection risk; mouth sores; nausea; liver issues signaled by jaundice; heart complications; kidney dysfunction indicated by changes in urine output or swelling; and lung problems like difficulty breathing.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with Fanconi anemia.

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My heart, liver, kidneys, and lungs are functioning well.

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I am not pregnant or breastfeeding and agree to pregnancy tests and avoiding pregnancy while in the study.

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I have a severe blood disorder such as SAA, MDS, or AML.

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My donor matches me genetically but is not my sibling.

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I am mostly active and can care for myself.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any ongoing serious infections.

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I have leukemia that has spread to my brain.

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I am not pregnant or breastfeeding.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ one year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~one year

This trial's timeline: 3 weeks for screening, Varies for treatment, and one year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Graft Failure or Rejection

Secondary study objectives

Post-transplant severe morbidity and mortality

Other study objectives

Graft Versus Host Disease

Leukemic Relapse

Secondary malignancies

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Arm C: High Risk PatientsExperimental Treatment6 Interventions

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 II: Arm B: Intermediate Risk PatientsExperimental Treatment6 Interventions

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 III: Arm A: Good Risk PatientsExperimental Treatment6 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

G-CSF

2014

Completed Phase 4

~1610

Cyclophosphamide

2010

Completed Phase 4

~2310