Clinical trial NCT06412497: MT2023-20: Hematopoietic Cell Transplant With Reduced Intensity Conditioning and Post-transplant Cyclophosphamide for Severe Aplastic Anemia and Other Forms of Acquired Bone Marrow Failure.
Official title: MT2023-20: Hematopoietic Cell Transplant With Reduced Intensity Conditioning and Post-transplant Cyclophosphamide for Severe Aplastic Anemia and Other Forms of Acquired Bone Marrow Failure.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Severe Aplastic Anemia
Acquired Amegakaryocytic Thrombocytopenia
Acquired Pure Red Cell Aplasia
Paroxysmal Nocturnal Hemoglobinuria
Keywords: HCT
RIC
SAA
PTCy
aAT
aPRCA
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2024-05-14
Enrollment: 60
Sex: ALL
Minimum age (years): 0
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of grade 3-4 acute GvHD
timeFrame: 1 year post HCT
measure: Incidence of chronic GvHD-free, failure-free survival (GFFS)
timeFrame: 1 year post HCT
measure: Incidence of chronic GvHD-free survival
timeFrame: 1 year post HCT
Secondary outcomes:
measure: Incidence of failure-free survival (GFFS)
timeFrame: 2 years post HCT
measure: Incidence of neutrophil recovery
timeFrame: Day 42 post HCT
measure: Incidence of platelet recovery
timeFrame: 6 months post HCT
measure: Incidence of grade 3-4 acute GvHD
timeFrame: 100 days post HCT
measure: Incidence of any chronic GvHD
timeFrame: 1 year post HCT
measure: Overall survival
timeFrame: 1 and 2 years post HCT
measure: Incidence of chronic GvHD-free survival
timeFrame: 2 years post HCT
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Cancer Center
state: Minnesota
Study officials:
References: