Memorial Sloan Kettering Cancer Center
Hematopoietic Cell Transplantation/HCT involves receiving healthy blood-forming cells (stem cells) from a donor to replace the diseased or damaged cells in participants' bone marrow. The researchers think giving participants treatment with fludarabine and dexamethasone, drugs that lower the activity of the body's immune system (immune suppression), before standard conditioning therapy and HCT may help prevent serious side effects, including graft failure and GvHD. In this study, depending on how participants' body responds to the fludarabine and dexamethasone, the study doctor may decide participants should receive another drug, called cyclophosphamide, instead of fludarabine. In addition, depending on the results of participants' routine blood tests, participants may receive the drugs bortezomib and rituximab, which also help with immune suppression.
Inclusion Criteria: * Age ≥ 2 and ≤ 50 years * Suitable haploidentical donor. * Performance score ≥ 70% by Karnofsky Performance Scale or 0 to 1 by ECOG (age \> 16 years), or Lansky Play-Performance Scale ≥ 70% (age ≤ 16 years). * Adequate major organ system function as demonstrated by: * For patients ≥ 18 years of age: * eGFR ≥ 50 mL/min by Cockcroft-Gault formula Formula: ((140 - Age) x Weight (kg)) / (72 x Serum Creatinine (mg/dL) Female Adjustment: Multiply result by 0.85 * For patients \< 18 years of age: * Serum creatinine clearance: glomerular filtration rate \[GFR\]) must be…
PK-guided fludarabine dosing will be used for each of the 2 cycles, using the InsightRx DoseMeRx platform.
Cyclophosphamide will be administered Post-Transplant
Tacrolimus will be administered beginning on day +5
Mycophenolate mofetil (MMF) will be administered three times daily starting on day +5.
The dose and schedule of ATG will be determined according to the nomogram in Appendix A
Standard Regimen: Dexamethasone on days -68 to -64 and days -40 to -36.
Bortezomib on days -71, -68, -65, -61, -43, -40, -37, and -33
Rituximab on days -71, -58, -43, and -30.