TBI Dose De-escalation for Fanconi Anemia

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00352976
• Date of registration: 14/07/2006
• Prospective Registration: No
• Primary sponsor: Masonic Cancer Center, University of Minnesota
• Public title: TBI Dose De-escalation for Fanconi Anemia
• Scientific title: Total Body Irradiation Dose De-escalation Study in Patients With Fanconi Anemia Undergoing Alternate Donor Hematopoietic Cell Transplantation
• Date of first enrolment: May 18, 2006
• Target sample size: 88
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00352976
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2/Phase 3

Countries of recruitment

United States

Contacts

• Name: Margaret L MacMillan, M.D.
• Affiliation: University of Minnesota Medical Center

Key inclusion & exclusion 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).



Age minimum: N/A
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Fanconi Anemia

Intervention(s)

Procedure: Total Body Irradiation

Drug: Fludarabine

Drug: Sirolimus

Drug: Cyclophosphamide

Procedure: Bone Marrow Transplantation

Drug: Mycophenolate Mofetil

Primary Outcome(s)

Incidence of neutrophil recovery (absolute neutrophil count =500/µL for three consecutive days) . [Time Frame: by day 42]

Secondary Outcome(s)

Immune reconstitution . [Time Frame: at 100 days, 6 month and one year]

Incidence of acute graft-versus-host disease (GVHD) [Time Frame: at 100 days.]

Incidence of grade =3 regimen related toxicity . [Time Frame: at day 100]

Incidence of infections . [Time Frame: at 100 days, 6 months and one year]

Incidence of secondary graft failure at 100 days. [Time Frame: 100 days]

Incidence of chronic GVHD . [Time Frame: at one year]

Probability of survival . [Time Frame: at one year]

Secondary ID(s)

MT2006-05

0605M85788

Source(s) of Monetary Support

Please refer to primary and secondary sponsors