Allo HSCT Using RIC for Hematological Diseases | Aplastic Anemia and MDS International Foundation

Clinical Trial: NCT02661035

Allo HSCT Using RIC for Hematological Diseases
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This is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen followed by a related or unrelated donor stem cell infusion. The primary objective is to evaluate rates of acute graft-versus-host disease (GVHD) grades II-IV and chronic GVHD with an updated GVHD prophylaxis of tacrolimus and mycophenolate mof

Study Date: 
Tue, 03/01/2016 to Wed, 06/01/2022
Bone Marrow Disease(s): 
myelodysplastic syndromes (MDS)
Drug: Allopurinol 300 mg/day (for peds -150 mg/m^2/day), day -6 and continue through day 0 or longer if clinically indicated Other Name: Zyloprim Drug: Fludarabine 30 mg/m^2 IV over 1 hour, day -6, -5, -4, -3 and -2 Other Name: Fludara Drug: Cyclophosphamide 50 mg/kg IV over 2 hours, day -6 Other Name: Cytoxan Drug: ATG Only for patients with an unrelated donor (URD) and NO multi-agent chemotherapy 3 months prior to transplant. ATG will be administered IV every 12 hours for 6 doses on days -6, -5, and -4 according to institutional guidelines. Methylprednisolone 1 mg/kg IV administered immediately prior to each dose of ATG (6 doses). Other Name: Anti-thymocyte globulin Radiation: TBI All patients who have had previous radiation therapy or TBI will be seen by Radiation Oncology prior to entrance on the protocol for approval for additional 200 cGy of TBI. TBI may be delivered by local guidelines provided the effective dose is equivalent to what is recommended in the TBI Guidelines. The dose of TBI will be 200 cGy given in a single fraction on day -1. Other Name: Total body irradiation Drug: Tacrolimus All patients will receive tacrolimus therapy beginning on day -3. Initial dosing of tacrolimus will be 0.03 - 0.05 mg/kg/day IV; if the recipient body weight is <40 kg, dosing will be 3 times daily, and if ≥ 40 kg, twice daily or per current institutional guidelines. An attempt will be made to maintain a trough level of 5-10 ng/mL and subsequent dose modifications will be provided by the pharmacist. Once the patient can tolerate oral medications and has a reasonable oral intake, tacrolimus will be converted to an oral form based on the current IV dose providing normal renal and hepatic function and no major drug interactions. The timing of the tacrolimus taper will be at the discretion of the treating physician, but in general: Taper begins at day +100 +/- 10 days, if the patient is stably engrafted and has no active GVHD. Taper to zero by reducing dose by approximately 10% a week (rounded to nearest pill size), with a goal to discontinue by month 6 post-HCT. Other Name: Prograf Drug: MMF 3 gram/day IV/PO for patients who are ≥ 40 kg divided in 2 or 3 doses. In obese patients (>125% IBW) 15 mg/kg every 12 hours may be considered. Pediatric patient (<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours beginning day -3. MMF dosing will be monitored and altered as clinically appropriate based on institutional guidelines. Patients will be eligible for MMF dosing and pharmacokinetics studies. MMF will stop at day +30 or 7 days after engraftment, whichever day is later, if no acute GVHD. (Definition of engraftment is 1st day of 3 consecutive days of absolute neutrophil count [ANC) ≥ 0.5 x 109 /L]). If no donor engraftment, MMF will continue as long as clinically indicated. Other Name: Mycophenolate Mofetil Biological: Peripheral Blood Stem Cells On day 0, patients will receive an allogeneic transplant using PBSC which are CD34+ selected as the donor graft. The graft will be infused over 15-60 minutes after premedication with acetaminophen 650 mg PO and diphenhydramine 25 mg PO/IV with doses adjusted for pediatric patients. Biological: Related or Unrelated Bone Marrow Cells On day 0, a target dose of 3 x 10^8 nucleated cells/kg recipient weight will be collected. The graft will be infused over 15-60 minutes after premedication with acetaminophen 650 mg PO and diphenhydramine 25 mg PO/IV with doses adjusted for pediatric patients.