What's the purpose of this trial?
A phase II trial of a reduced intensity conditioned (RIC) allogeneic hematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy) for idiopathic severe aplastic anemia (SAA), paroxysmal nocturnal hemoglobinuria (PNH), acquired pure red cell aplasia (aPRCA), or acquired amegakaryocytic thrombocytopenia (aAT) utilizing population pharmacokinetic (popPK)-guided individual dosing of pre-transplant conditioning and differential dosing of low dose total body irradiation based on age, presence of myelodysplasia and/or clonal hematopoiesis.
This trial is currently open and accepting patients.
What will happen during the trial?
You may be able to join this trial if you:
The following criteria is a partial list of reasons why patients may be
eligible to participate in this clinical trial. Further evaluation with a medical professional is
required.
Inclusion Criteria:
* Idiopathic Severe Aplastic Anemia (SAA), characterized by one of the following:
1. Refractory cytopenia(s), with 1+ of the following:
1. Platelets \<20,000/uL or transfusion dependent
2. Absolute neutrophil count \<500/uL without hematopoietic growth factor support
3. Absolute reticulocyte count \<60,000/uL AND bone marrow cellularity \<50% (with \< 30% residual hematopoietic cells)
2. Early myelodysplastic features (bone marrow (BM) blasts \<5%), without history of MDS/AML pre-treatment.
3. Idiopathic SAA with post-HCT graft failure (blood/marrow donor chimerism \<5%) requiring a 2nd allogeneic HCT
* Paroxysmal Nocturnal Hemoglobinuria (PNH), including AA-PNH overlap syndrome, acquired pure red cell aplasia (aPRCA), or acquired amegakaryocytic thrombocytopenia (aAT), characterized by one of the following:
1. Refractory cytopenia(s), with 1+ of the following:
1. Platelets \<20,000/uL or transfusion dependent
2. Absolute neutrophil count \<500/uL without hematopoietic growth factor support
3. Absolute reticulocyte count \<60,000/uL or red cell transfusion dependent AND Bone marrow evidence of 1 to 3-lineage aplasia OR peripheral blood PNH clone \>/= 10%
2. Early myelodysplastic features (bone marrow (BM) blasts \<5%) without history of MDS/AML pre-treatment.
3. Idiopathic PNH, aPRCA, or aAT with post-HCT graft failure (blood/marrow donor chimerism \<5%) requiring a 2nd allogeneic HCT
* Adequate organ function within 30 days of conditioning regimen
Exclusion Criteria:
* Pregnant, breastfeeding or intending to become pregnant during the study. Persons of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days of the start of treatment
* Uncontrolled infection
* Evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
* Known allergy to any of the study components
* Prior radiation therapy deemed excessive by radiation therapist for proposed low dose TBI exposure on this protocol
* Diagnosis of an inherited bone marrow failure disorder such as Fanconi anemia, Telomere biology disorder, or Schwachman-Diamond syndrome, unless reviewed by the principal investigator and deemed appropriate for this approach (e.g. GATA2 deficiency)
* Advanced myelodysplastic syndrome (MDS; BM blasts \>5%) or acute myeloid leukemia
* Psychiatric illness/social situations that, in the judgement of the enrolling Investigator, would limit compliance with study requirements
* Other illness or a medical issue that, in the judgement of the enrolling Investigator, would exclude the patient from participating in this study
Additional Trial Information
Phase 2
Enrollment: 60 patients (estimated)
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