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.

Phase 2

Recruiting

• Conditions: Acquired Amegakaryocytic Thrombocytopenia; Acquired Pure Red Cell Aplasia; Severe Aplastic Anemia; Paroxysmal Nocturnal Hemoglobinuria
• Interventions: Drug: Rituximab; Drug: Rabbit ATG; Drug: Cyclophosphamide; Drug: Fludarabine; Radiation: Total Body Irradiation; Biological: Cell Infusion; Drug: Post-Transplant G-CSF; Drug: Tacrolimus; Drug: Mycophenolate Mofetil

• Registration Number: NCT06412497
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

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 pharmacoki...

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2024-05-09
• Study First Submitted QC: 2024-05-09
• Study First Posted: 2024-05-14
• Status Verified: 2024-06
• Study Start: 2024-06-05
• Last Update Submitted: 2024-06-06
• Last Update Posted: 2024-06-10
• Primary Completion: 2035-05-01
• Study Completion: 2036-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B: Clonal hematopoiesis	Fludarabine	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.
Arm B: Clonal hematopoiesis	Total Body Irradiation	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.
Arm B: Clonal hematopoiesis	Cell Infusion	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.
Arm B: Clonal hematopoiesis	Rabbit ATG	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.
Arm A: No clonal hematopoiesis	Total Body Irradiation	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.
Arm A: No clonal hematopoiesis	Post-Transplant G-CSF	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.
Arm A: No clonal hematopoiesis	Cell Infusion	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.
Arm B: Clonal hematopoiesis	Post-Transplant G-CSF	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.
Arm A: No clonal hematopoiesis	Rabbit ATG	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.
Arm A: No clonal hematopoiesis	Rituximab	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.
Arm A: No clonal hematopoiesis	Fludarabine	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.
Arm A: No clonal hematopoiesis	Cyclophosphamide	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.
Arm A: No clonal hematopoiesis	Tacrolimus	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.
Arm A: No clonal hematopoiesis	Mycophenolate Mofetil	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.
Arm B: Clonal hematopoiesis	Rituximab	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.
Arm B: Clonal hematopoiesis	Cyclophosphamide	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.
Arm B: Clonal hematopoiesis	Tacrolimus	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.
Arm B: Clonal hematopoiesis	Mycophenolate Mofetil	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.

Primary Outcome Measures

Name	Time	Method
Incidence of chronic GvHD-free, failure-free survival (GFFS)	1 year post HCT	Incidence of chronic GvHD-free, failure-free survival (GFFS) 1 year post HCT
Incidence of chronic GvHD-free survival	1 year post HCT	Incidence of chronic GvHD-free survival at 1 year post HCT
Incidence of grade 3-4 acute GvHD	1 year post HCT	Incidence of grade 3-4 acute graft-versus host disease (GvHD) at 1 year post HCT.

Secondary Outcome Measures

Name	Time	Method
Incidence of neutrophil recovery	Day 42 post HCT	Incidence of neutrophil recovery at day 42 post HCT
Incidence of platelet recovery	6 months post HCT	Incidence of platelet recovery at 6 months post HCT
Incidence of grade 3-4 acute GvHD	100 days post HCT	Incidence of grade 3-4 acute GvHD at 100 days post HCT
Overall survival	1 and 2 years post HCT	Overall survival at 1 and 2 years
Incidence of chronic GvHD-free survival	2 years post HCT	Incidence of chronic GvHD-free survival at 2 years post HCT
Incidence of failure-free survival (GFFS)	2 years post HCT	Incidence of chronic GvHD-free, failure-free survival (GFFS) 2 years post HC
Incidence of any chronic GvHD	1 year post HCT	Incidence of any chronic GvHD at 1 year post HCT

Trial Locations

Locations (1)

University of Minnesota Masonic Cancer Center; 🇺🇸 Minneapolis, Minnesota, United States