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.

NCT06412497 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2023LS101
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

HCT; RIC; SAA; PTCy; aAT; aPRCA

Outcome Measures

Primary Outcomes (3)

• Incidence of grade 3-4 acute GvHD

  Incidence of grade 3-4 acute graft-versus host disease (GvHD) at 1 year post HCT.

  1 year post HCT

• Incidence of chronic GvHD-free, failure-free survival (GFFS)

  Incidence of chronic GvHD-free, failure-free survival (GFFS) 1 year post HCT

  1 year post HCT

• Incidence of chronic GvHD-free survival

  Incidence of chronic GvHD-free survival at 1 year post HCT

  1 year post HCT

Secondary Outcomes (7)

• Incidence of failure-free survival (GFFS)

  2 years post HCT

• Incidence of neutrophil recovery

  Day 42 post HCT

• Incidence of platelet recovery

  6 months post HCT

• Incidence of grade 3-4 acute GvHD

  100 days post HCT

• Incidence of any chronic GvHD

  1 year post HCT

Study Arms (2)

Arm A: No clonal hematopoiesis

EXPERIMENTAL

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.

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

Arm B: Clonal hematopoiesis

EXPERIMENTAL

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.

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

Interventions

Rituximab DRUG

For patients with EBV IgG seropositivity or EBV PCR positivity on pre-transplant evaluations, Rituximab 375 mg/m2 is given IV once on day -14 (+/-2 day) in the outpatient setting. Pre-medicate 30 minutes prior to rituximab with methylprednisolone (1 mg/kg) IV, acetaminophen 15 mg/kg (maximum 650mg) IV or PO and diphenhydramine 1 mg/kg (maximum 50mg) IV or PO.

Arm A: No clonal hematopoiesis; Arm B: Clonal hematopoiesis

Rabbit ATG DRUG

Rabbit ATG will be administered at doses and days indicated above, infused through a 0.22 micrometer filter over 4-6 hours. Pre-medicate 30 minutes prior to ATG infusion with methylprednisolone 1 mg/kg IV, (max dose = 125 mg), acetaminophen 15 mg/kg dose (max dose = 650 mg) enterally and diphenhydramine 1 mg/kg/dose (max dose = 50 mg) enterally or IV.

Also known as: Thymoglobulin

Arm A: No clonal hematopoiesis; Arm B: Clonal hematopoiesis

Cyclophosphamide DRUG

Cyclophosphamide 14.5 mg/kg is be given as a 2-hour infusion on day -6. If the patient is obese (actual body weight (ABW) \>/= 125% of the ideal body weight (IBW)), cyclophosphamide should be dosed using the adjusted body weight (AdjBW): 0.5(ABW-IBW) + IBW. Uroprotection with MESNA (14.5 mg/kg/day) in IV continuous infusion will be provided per institutional guidelines. Hyperhydration is not required for 14.5 mg/kg cyclophosphamide doses. Cyclophosphamide will be administered at 50 mg/kg using ABW over 2 hours on days +3 and +4. If the patient is obese (ABW \>/= 125% of the ideal body weight (IBW)), cyclophosphamide should be dosed using the adjusted body weight (AdjBW): 0.5(ABW-IBW) + IBW. Uroprotection with MESNA (50 mg/kg/day) in IV continuous infusion as well as hyperhydration will be provided per institutional guidelines.

Arm A: No clonal hematopoiesis; Arm B: Clonal hematopoiesis

Fludarabine DRUG

For all patients, fludarabine dosing will be model-based using Bayesian methodology IV every 24 hours on days -6 to -3 with a cumulative area under the curve (cAUC) of 20 mg\*hr/L.

Arm A: No clonal hematopoiesis; Arm B: Clonal hematopoiesis

Total Body Irradiation RADIATION

For patients age \>/= 25 years, with myelodysplasia, or clonal hematopoiesis, total body irradiation will be 4 Gy, provided in two fractions on day -1. For all other patients, total body irradiation will be 2 Gy provided in a single fraction on day -1. Each dose of 2 Gy will be given at a dose rate between 1 and 1.9 Gy/minute prescribed to the midplane of the patient at the level of the umbilicus.

Also known as: TBI

Arm A: No clonal hematopoiesis; Arm B: Clonal hematopoiesis

Cell Infusion BIOLOGICAL

On day 0 the cells will be infused per cell source specific institutional guidelines.

Arm A: No clonal hematopoiesis; Arm B: Clonal hematopoiesis

Post-Transplant G-CSF DRUG

Beginning on day +5, patients will receive G-CSF SQ or IV 5 micrograms/kg once daily until post-nadir ANC \> 1500/μL for 3 consecutive days or \>3000/μL for 1 day.

Also known as: Filgrastim

Arm A: No clonal hematopoiesis; Arm B: Clonal hematopoiesis

Tacrolimus DRUG

Tacrolimus will begin on day +5 at an initial dose of 0.03 mg/kg/day IV via continuous infusion. Goal trough levels will be 10-15 ug/mL until day +14 posttransplant, then decreased to a goal of 5-10 ng/mL thereafter. In the absence of GvHD, tacrolimus will discontinue at day +180 without a taper.

Arm A: No clonal hematopoiesis; Arm B: Clonal hematopoiesis

Mycophenolate Mofetil DRUG

Mycophenolate mofetil (MMF) therapy will begin on day +5. For pediatric service patients dosing of MMF will be 15 mg/kg/dose (max = 1000 mg) three times daily. For adult service patients dosing of MMF will be 15 mg/kg/dose (max = 1500 mg) twice daily. The same dosage is used orally or intravenously. Consider dose modification and/or pharmacokinetic measurements if renal and/or hepatic impairment (GFR\<25 mL/minute corrected). Stop MMF at Day +35 or 7 days after engraftment achieved (ANC\>500 x 106 neutrophils/L x 3 days) if later than day +35. If sufficient acute GvHD is observed to require systemic therapy, MMF should be continued for 7 days after initiation of systemic therapy. Afterward, use of MMF is at the discretion of the treating physician.

Also known as: MMF

Arm A: No clonal hematopoiesis; Arm B: Clonal hematopoiesis

Eligibility Criteria

• Age: 0 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Idiopathic Severe Aplastic Anemia (SAA), characterized by one of the following:
• Refractory cytopenia(s), with 1+ of the following:
• Platelets \<20,000/uL or transfusion dependent
• Absolute neutrophil count \<500/uL without hematopoietic growth factor support
• Absolute reticulocyte count \<60,000/uL AND bone marrow cellularity \<50% (with \< 30% residual hematopoietic cells)
• Early myelodysplastic features (bone marrow (BM) blasts \<5%), without history of MDS/AML pre-treatment.
• 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:
• Refractory cytopenia(s), with 1+ of the following:
• Platelets \<20,000/uL or transfusion dependent
• Absolute neutrophil count \<500/uL without hematopoietic growth factor support
• 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%
• Early myelodysplastic features (bone marrow (BM) blasts \<5%) without history of MDS/AML pre-treatment.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Aplastic; Acquired amegakaryocytic thrombocytopenia; Hemoglobinuria, Paroxysmal

Interventions

Rituximab; thymoglobulin; Cyclophosphamide; fludarabine; Whole-Body Irradiation; Insulin Infusion Systems; Filgrastim; Tacrolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Anemia, Hemolytic; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Drug Delivery Systems; Drug Therapy; Infusion Pumps; Equipment and Supplies; Artificial Organs; Surgical Equipment; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Central Study Contacts

Christen Ebens, MD, MPH

CONTACT

612-624-1791; ebens012@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2024
• First Posted: May 14, 2024
• Study Start: June 5, 2024
• Primary Completion (Estimated): May 1, 2035
• Study Completion (Estimated): May 1, 2036
• Last Updated: June 19, 2025

Record last verified: 2025-06

Locations

US (1)