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.

Browse trials for

• Anemia, Aplastic 343
• Hemoglobinuria, Paroxysmal 188

Keywords

• HCT
• RIC
• SAA
• PTCy
• aAT
• aPRCA

Anemia, Aplastic

343 studies on the registry are indexed under Anemia, Aplastic; 99 are open to participants now.

This study's planned enrollment of 60 is above the median of 39 across 268 interventional studies indexed under Anemia, Aplastic.

Lead sponsor

Masonic Cancer Center, University of Minnesota is the lead sponsor of 284 studies on the registry; 34 are open to participants now.

Of its 39 completed or terminated interventional studies of FDA-regulated products, 28 (72%) have results posted.

Study arms

• Experimental
  Arm A: No clonal hematopoiesis

  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

• Experimental
  Arm B: Clonal hematopoiesis

  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

• DrugRituximab

  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.

• DrugRabbit ATG

  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

• DrugCyclophosphamide

  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.

• DrugFludarabine

  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.

• RadiationTotal Body Irradiation

  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

• BiologicalCell Infusion

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

• DrugPost-Transplant G-CSF

  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

• DrugTacrolimus

  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.

• DrugMycophenolate Mofetil

  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

Primary outcomes

1. Incidence of grade 3-4 acute GvHD

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

   Time frame: 1 year post HCT

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

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

   Time frame: 1 year post HCT

3. Incidence of chronic GvHD-free survival

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

   Time frame: 1 year post HCT

Secondary outcomes

1. Incidence of failure-free survival (GFFS)

   Incidence of chronic GvHD-free, failure-free survival (GFFS) 2 years post HC

   Time frame: 2 years post HCT

2. Incidence of neutrophil recovery

   Incidence of neutrophil recovery at day 42 post HCT

   Time frame: Day 42 post HCT

3. Incidence of platelet recovery

   Incidence of platelet recovery at 6 months post HCT

   Time frame: 6 months post HCT

4. Incidence of grade 3-4 acute GvHD

   Incidence of grade 3-4 acute GvHD at 100 days post HCT

   Time frame: 100 days post HCT

5. Incidence of any chronic GvHD

   Incidence of any chronic GvHD at 1 year post HCT

   Time frame: 1 year post HCT

6. Overall survival

   Overall survival at 1 and 2 years

   Time frame: 1 and 2 years post HCT

7. Incidence of chronic GvHD-free survival

   Incidence of chronic GvHD-free survival at 2 years post HCT

   Time frame: 2 years post HCT