Sirolimus & Mycophenolate Mofetil as GVHD Prophylaxis in Myeloablative, Matched Related Donor HCT
Leukemia, Lymphoma, Non-Hodgkin, Hematologic Diseases
About this trial
This is an interventional treatment trial for Leukemia
Eligibility Criteria
Inclusion Criteria: Disease Categories: (one of the following) AML, age 2 - 60 years beyond 2nd remission or relapsed/refractory disease AML, age 51-60 years of age, in first or subsequent remission or relapsed/refractory disease AML with multilineage dysplasia ALL, age 2 - 60 years beyond 2nd remission or relapsed/refractory disease ALL, age 51 - 60 years in first or subsequent remission or relapsed/refractory disease CML Beyond 2nd chronic phase or in blast crisis MDS; Includes World Health Organization classifications of refractory anemia with excess blasts-1 (RAEB-1), RAEB-2 and therapy-related MDS Myeloproliferative disorders; MDS with poor long-term survival including myeloid metaplasia and myelofibrosis High risk NHL in first remission Relapsed or refractory NHL HL beyond first remission Males and females of any ethnic background 2 - 60 years of age Karnofsky Performance Status ≥ 70% or Lansky performance status > 70% for patients < 16 years of age. Matched related donor identified: 6/6 HLA-A, B and DRB1 Willingness to take oral medications during the transplantation period Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Prior myeloablative allogeneic or autologous HCT HIV infection Pregnant Lactating females Evidence of uncontrolled active infection Organ Dysfunction: Serum creatinine > 1.5 mg/dL or 24 hour creatinine clearance < 50 ml/min Direct bilirubin, ALT or AST > 2 x ULN In adults DLCO < 60% predicted and in children room air oxygen saturation < 92% In adults, left ventricular ejection fraction < 45% and in children, shortening fraction < 26% Fasting Cholesterol > 300 mg/dL or Triglycerides > 300 mg/dL while on lipid-lowering agents. Patients receiving investigational drugs unless cleared by the PI. Patients with prior malignancies except basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent > 5 years will be allowed. Cancer treated with curative intent ≤ 5 years will not be allowed with PI approval.
Sites / Locations
- Stanford University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Regimen Treatment 1
Regimen Treatment 2
Regimen Treatment 3
For subjects 18-60 years old with lymphoma: (BCNU+ VP-16 +CY) BCNU 15 mg / kg (maximum dose 550 mg/m² actual body weight) on day -6. VP 60 mg / kg on day 4 and CY 100 mg / kg on day -2. Followed by Sirolimus and MMF as prophylaxis
For subjects 18-50 years old with AML, ALL or CML: (VP-16 +CY+ FBI) Patients aged 18-50 years with AML, ALL or CML: FTBI 1320 cGy delivered in 11 120 cGy fractions over 4 days on days -8 through -5. VP 60 mg / kg on day -4 and CY 60 mg / kg on day -2. Followed by Sirolimus and MMF as prophylaxis
For subjects 51-60 years with MDS, AML or ALL or 18-60 with MDS, secondary AML pr non-CML myeloproliferative disease: (BU+ VP-16 +CY) BU 1 mg/kg every 6 hours X 14 doses on days -9 through -6 with target concentration at steady state of X 800 ng / ml based on first dose pharmacokinetics. VP 60 mg / kg on day -5 and CY 45 mg / kg per day -2 days on day -3 and day -2. Followed by Sirolimus and MMF as prophylaxis