A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

Summary

The purpose of this clinical trial is to compare drug combinations to learn which drugs work best to prevent graft-versus-host-disease (GVHD) in people who have received a stem cell transplant. The source of stem cells is from someone who is not related and has a different blood cell type than the study participant. The researchers will compare the new drug combination to a standard drug combination. They will also learn about the safety of each drug combination. Participants will: * Receive the standard or new drug combination after transplant * Visit the doctor's office for check-ups and tests after transplant that are routine for most transplant patients * Take surveys about physical and emotional well-being * Give blood and stool samples.

Description

Eligibility

Age range

18–66 years

Sex

All

Healthy volunteers

No

Interventions

• Drug
  Conditioning Regimen A

  Busulfan and fludarabine Recommended schedule as below: * Days -6 to -3: Busulfan ≥ 9 mg/kg total dose (IV or PO) with pharmacokinetic (PK) monitoring recommended as per institutional practice to achieve a daily area under the curve (AUC) target of 4800-5300 μM\*min47 or busulfan plasma exposure units (BPEU) 19.7-21.75 mg x h/L48. * Days -6 to -2: Flu 30 mg/m2/day (adjusted for renal function) is administered over a 30-60 minute IV infusion (maximum cumulative dose, 150 mg/m2).

• Drug
  Conditioning Regimen B

  Fludarabine and TBI The recommended fludarabine plus TBI regimen is the following: * Days -7, -6 and -5: Flu (30 mg/m2/day, maximum cumulative dose, 90 mg/m2), IV * Days -4 to -1: TBI (150 cGy administered twice daily, 1200 cGy total dose) * Radiation sources, dose rates, and shielding follow institutional practice. * Although not required, it is recommended that palifermin be used to mitigate the risk of mucosal toxicity with this regimen.

• Drug
  Conditioning Regimen C

  Fludarabine and busulfan (Flu/Bu) The recommended Flu/Bu regimen is the following: * Days -6 to -2: Flu (30 mg/m2/day, recommended total dose of 150 mg/m2, but not exceeding 180 mg/m2), IV Busulfan options * Days -5 to -4: Busulfan without PK - Busulfan 3.2 mg/kg/day IV or oral equivalent; total dose of 6.4 mg/kg IV or oral equivalent respectively * Days -5 to -4: Busulfan with PK - target doses to AUC of 4000 μMol/min or BPEU of 16.43 mg x h/L (total BPEU of 65.72 mg x h/L) or less is allowed.

• Drug
  Conditioning Regimen D

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