Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of failure-free survival (GFFS) | Incidence of chronic GvHD-free, failure-free survival (GFFS) 2 years post HC | 2 years post HCT |
| Incidence of neutrophil recovery | Incidence of neutrophil recovery at day 42 post HCT |
Not provided
Inclusion Criteria:
Idiopathic Severe Aplastic Anemia (SAA), characterized by one of the following:
Refractory cytopenia(s), with 1+ of the following:
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:
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
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Meera Srikanthan, MD | Contact | (612) 626-2961 | srika038@umn.edu |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Minnesota Masonic Cancer Center | Recruiting | Minneapolis | Minnesota | 55455 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 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. |
|
|
| 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. |
|
| 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. |
|
| 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. |
|
|
| Cell Infusion | Biological | On day 0 the cells will be infused per cell source specific institutional guidelines. |
|
| 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. |
|
|
| 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. |
|
| 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. |
|
|
| Day 42 post HCT |
| Incidence of platelet recovery | Incidence of platelet recovery at 6 months post HCT | 6 months post HCT |
| Incidence of grade 3-4 acute GvHD | Incidence of grade 3-4 acute GvHD at 100 days post HCT | 100 days post HCT |
| Incidence of any chronic GvHD | Incidence of any chronic GvHD at 1 year post HCT | 1 year post HCT |
| Overall survival | Overall survival at 1 and 2 years | 1 and 2 years post HCT |
| Incidence of chronic GvHD-free survival | Incidence of chronic GvHD-free survival at 2 years post HCT | 2 years post HCT |
| ID | Term |
|---|---|
| D000741 | Anemia, Aplastic |
| C538172 | Acquired amegakaryocytic thrombocytopenia |
| D006457 | Hemoglobinuria, Paroxysmal |
| ID | Term |
|---|---|
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D000080983 | Bone Marrow Failure Disorders |
| D001855 | Bone Marrow Diseases |
| D000743 | Anemia, Hemolytic |
| D009190 | Myelodysplastic Syndromes |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069283 | Rituximab |
| C512542 | thymoglobulin |
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| D014916 | Whole-Body Irradiation |
| D007332 | Insulin Infusion Systems |
| D000069585 | Filgrastim |
| D016559 | Tacrolimus |
| D009173 | Mycophenolic Acid |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
| D016503 | Drug Delivery Systems |
| D004358 | Drug Therapy |
| D007260 | Infusion Pumps |
| D004864 | Equipment and Supplies |
| D001187 | Artificial Organs |
| D013523 | Surgical Equipment |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D001685 | Biological Factors |
| D018942 | Macrolides |
| D007783 | Lactones |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
Not provided
Not provided