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.

University of Minnesota (UMN)

Status and phase: Enrolling; Phase 2

Conditions: Paroxysmal Nocturnal Hemoglobinuria; Acquired Pure Red Cell Aplasia; Acquired Amegakaryocytic Thrombocytopenia; Severe Aplastic Anemia

Treatments: Drug: Rituximab; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Rabbit ATG; Radiation: Total Body Irradiation; Drug: Post-Transplant G-CSF; Drug: Fludarabine; Biological: Cell Infusion; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT06412497

2023LS101

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: Under 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Arm A: No clonal hematopoiesis

Experimental group

Description:

Participants 25 years of age and younger with no clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.

Treatment:

Drug: Cyclophosphamide

Drug: Post-Transplant G-CSF

Biological: Cell Infusion

Drug: Fludarabine

Radiation: Total Body Irradiation

Drug: Rabbit ATG

Drug: Mycophenolate Mofetil

Drug: Tacrolimus

Drug: Rituximab

Arm B: Clonal hematopoiesis

Experimental group

Description:

Participants 25-75 years old and/or with clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.

Treatment:

Drug: Cyclophosphamide

Drug: Post-Transplant G-CSF

Biological: Cell Infusion

Drug: Fludarabine

Radiation: Total Body Irradiation

Drug: Rabbit ATG

Drug: Mycophenolate Mofetil

Drug: Tacrolimus

Drug: Rituximab