Fludarabine Based RIC for Bone Marrow Failure Syndromes
Bone Marrow Failure Syndromes
About this trial
This is an interventional treatment trial for Bone Marrow Failure Syndromes focused on measuring Acquired aplastic anemia, Inherited bone marrow failure
Eligibility Criteria
Patients 0-22 years with acquired aplastic anemia or a diagnosed inherited bone marrow failure syndrome, and a fully Human leukocyte antigen (HLA)-matched (10/10) related donor.
Inclusion Criteria:
Patient:
- Ages 0-22 years at time of enrollment
Diseases:
Patients with severe or very severe acquired AA, defined by:
- Bone marrow biopsy demonstrating cellularity of <25% (at least 2 weeks from last dose of G-CSF), in addition to 2 of the following: absolute neutrophil count (ANC) <500/µL, platelets < 20,000/µL and absolute reticulocytes <40,000/µL
- Negative evaluation for inherited bone marrow failure conditions and negative evaluation for dysplasia or cytogenetic abnormalities associated with myelodysplastic syndromes
- Patients with concurrent paroxysmal nocturnal hemoglobinuria (PNH) clones are eligible, as long as they meet criteria for severe or very severe aplastic anemia as defined above
Patients with clinically diagnosed and/or genetically proven iBMF syndromes, resulting in chronic red blood cell or platelet-transfusion dependence and/or an absolute neutrophil count <500/µL. These disorders include, but are not limited to:
- Fanconi Anemia
- Dyskeratosis Congenita
- Severe Congenital Neutropenia
- Diamond-Blackfan Anemia
- Congenital Dyserythropoietic/Sideroblastic Anemias
- Congenital Amegakaryocytic Thrombocytopenia
- Shwachman-Diamond Syndrome
- Lansky or Karnofsky performance >60
- HLA matched related donor available.
- No active untreated infection
- Females of childbearing potential must have negative pregnancy test.
Organ Function:
- Serum creatinine <1.5xupper limit of normal for age Hepatic: Transaminases <5x normal
- Cardiac shortening fraction >27%
- Bilirubin <2.5x normal (unless elevation due to Gilberts disease).
Donor Selection Criteria:
- Donor selection will comply with U.S. Food and Drug Administration's Code of Federal Regulations
- Fully HLA-matched related donor.
- Donor must be at least 6 months of age
- Donor suitable for bone marrow collection and meets eligibility for donation, including fulfilling infectious disease criteria as per SOP, including HIV, Hepatitis B, Hepatitis C Polymerase chain reaction (PCR) negative.
- If subject has confirmed iBMF syndrome, donor must be evaluated for this disorder and testing must be negative
- Children's Hospital of Philadelphia (CHOP) bone marrow transplant (BMT) procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases.
- Donor evaluation and collection procedure as per CHOP Standard Operating Procedures (SOP)
Exclusion Criteria:
- Uncontrolled bacterial, viral or fungal infections
- HLA matched related donor unable to donate bone marrow.
- No eligible fully HLA-matched related donor
- Pregnant females
- Patients with a clinical diagnosis of Myelodysplastic syndrome (MDS) defined by combination of bone marrow dysplasia and classic cytogenetic lesion (Monosomy 7, Trisomy 8 eg.), with or without excess blasts.
- Patients with PNH without underlying bone marrow aplasia
Sites / Locations
- Children's Hospital of PhiladelphiaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Acquired Aplastic Anemia (AA)
Inherited Bone Marrow Failure Syndrome + Trilineage Aplasia
Inherited Bone Marrow Failure Syndrome no Trilineage Aplasia
Patients with severe or very severe acquired aplastic anemia (AA). Patients will receive a matched related donor bone marrow transplant following reduced intensity conditioning (RIC) including thymoglobulin (ATG), fludarabine and dose-reduced cyclophosphamide.
Patients with inherited bone marrow failure (iBMF) syndromes with trilineage aplasia includes those with diagnoses of Fanconi Anemia, Dyskeratosis Congenita, and related conditions. Patients will receive a matched related donor bone marrow transplant following conditioning with fludarabine, cyclophosphamide, thymoglobulin.
Patients with inherited bone marrow failure (iBMF) syndromes without trilineage aplasia includes those with diagnoses of Severe Congenital Neutropenia, Diamond-Blackfan Anemia, and related conditions. Patients will receive a matched related donor bone marrow transplant following conditioning with thymoglobulin, busulfan and fludarabine.