TBI Dose De-escalation for Fanconi Anemia

• Status: Completed
• Trial end date: 2020-10-09
• Target enrollment: 0
• Participant gender: All

Summary

This is a single arm, total body irradiation (TBI) trial. All patients will be prescribed TBI 300 cGy with the goal of evaluating secondary endpoints.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Masonic Cancer Center, University of Minnesota
• Treatments: Cyclophosphamide; Everolimus; Fludarabine; Fludarabine phosphate; Mycophenolate mofetil; Mycophenolic Acid; Sirolimus

Criteria

Inclusion Criteria:

Meeting the definition of standard risk or high risk Fanconi anemia as defined in the next two sections:

• Standard risk patients must be <18 years of age with a diagnosis of Fanconi anemia with aplastic anemia (AA), myelodysplastic syndrome without excess blasts, or high risk genotype as defined below:

• Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions:

• platelet count <20 * 10^9/L

• ANC <5 * 10^8/L

• Hemoglobin <8 g/dL

• Myelodysplastic syndrome (MDS) with multilineage dysplasia with or without chromosomal anomalies

• High risk genotype (e.g. IVS-4 or exon 14 FANCC mutations, or BRCA1 or 2 mutations)

• High risk patients must have one or more of the following high risk features:

• Advanced MDS (≥ 5% blast) or acute leukemia

• Require additional HSCT for graft failure

• History at any time of systemic fungal or gram negative infection

• Severe renal disease with a creatinine clearance <40 mL/min

• Age > 18 years

• Very high risk patients must have Advanced MDS (≥ 5% blast) or acute leukemia after initial hematopoietic stem cell transplant (HSCT)

• Patients must have an appropriate source of stem cells. Patients and donors will be typed for HLA-A, B, C and DRB1 using high resolution molecular typing.

• Adequate major organ function including:

• Cardiac: ejection fraction >45%

• Hepatic: bilirubin, AST or ALT, ALP <5 x normal

• Karnofsky performance status >70% or Lansky >50 (if < 16 years of age)

• Women of child-bearing age must be using adequate birth control and have a negative pregnancy test.

• Written consent.

Exclusion Criteria:

• Available HLA-genotypically identical related donor in standard risk patients.

• Active central nervous system (CNS) leukemia at time of study enrollment.

• History of squamous cell carcinoma of the head/neck/cervix within previous 2 years.

• Prior radiation therapy that prevents further total body irradiation (TBI).