A Phase II open-label, randomized controlled trial evaluating the effect of early versus conventional calcineurin inhibitor and mycophenolate mofetil initiation in graft-versus-host disease (GVHD) prophylaxis on the incidence of acute grade 2-4 GVHD in patients undergoing T cell replete haploidentical stem cell transplantation using post-transplant cyclophosphamide

After the institutional ethics committee’s approval and clinical trial registration, we will begin enrollment. After a written informed consent, 120 patients planned for haploidentical stem cell transplantation at our center will be enrolled. Stratified randomization (stratified for donor age above and below 30 years and by benign versus malignant indication) will be performed using computer-generated sequences and patients will be allocated to the following groups:

Group A: Cyclosporine from day 0  and mycophenolate mofetil from day 1

Group B: Cyclosporine and mycophenolate mofetil from day +5

 The initial dose of cyclosporine will be 2.5mg/kg IV Q12H. Cyclosporine levels will be monitored and doses will be titrated as per levels to achieve a trough level of 200 to 300 ng/ml for cyclosporine. Plasma samples for GVHD biomarker analysis will be collected on day 14 and day 28 and stored.

The dose of mycophenolate mofetil (MMF) will be 15mg per kg per dose PO TID with a maximum dose of 1g TID.

The primary outcome variable will be acute grade 2-4 GVHD while the secondary outcome variables will be CRS, graft failure, time to engraftment, chronic GVHD, 1 year overall survival, peak IL-6 levels, and plasma GVHD biomarkers measured on day 14 and day 28.