Hematopoietic cell transplant for severe blood disorders

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.

This study is testing a new way to prepare patients with severe blood disorders for a stem cell transplant to see if it can improve their recovery and reduce complications.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 0 Years to 75 Years
• Sex: All
• Sponsor: Masonic Cancer Center, University of Minnesota (Academic / other)
• Drugs / interventions: radiation, cyclophosphamide
• Locations: 1 site (Minneapolis, Minnesota)
• Trial ID: NCT06412497 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the use of reduced intensity conditioning (RIC) followed by allogeneic hematopoietic cell transplant (HCT) and post-transplant cyclophosphamide (PTCy) for patients with severe aplastic anemia and other forms of acquired bone marrow failure. The approach includes population pharmacokinetic-guided individual dosing of pre-transplant conditioning and differential dosing of low-dose total body irradiation based on patient-specific factors such as age and presence of myelodysplasia. The study aims to improve transplant outcomes and reduce complications associated with traditional conditioning regimens.

Who should consider this trial

Good fit: Ideal candidates include individuals with idiopathic severe aplastic anemia, paroxysmal nocturnal hemoglobinuria, acquired pure red cell aplasia, or acquired amegakaryocytic thrombocytopenia who meet specific clinical criteria.

Not a fit: Patients with non-idiopathic forms of aplastic anemia or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a safer and more effective treatment option for patients with severe aplastic anemia and related conditions.

How similar studies have performed: Other studies utilizing reduced intensity conditioning and post-transplant cyclophosphamide have shown promising results, indicating potential for success in this approach.

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

Where this trial is running

Minneapolis, Minnesota

• University of Minnesota Masonic Cancer Center — Minneapolis, Minnesota, United States (Recruiting)

Study contacts

• Study coordinator: Christen Ebens, MD, MPH

Conditions Severe Aplastic Anemia; Acquired Amegakaryocytic Thrombocytopenia; Acquired Pure Red Cell Aplasia; Paroxysmal Nocturnal Hemoglobinuria; HCT; RIC; SAA; PTCy