Sirolimus & Mycophenolate Mofetil as GvHD Prophylaxis in Myeloablative, Matched Related Donor HCT
Condition: Hematologic Diseases; Acute-graft-versus-host Disease; Leukemia; Non-Hodgkin Lymphoma (NHL); Hodgkin Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Hematologic Diseases; Graft vs Host Disease
Intervention: Sirolimus; Mycophenolate mofetil (MMF); Carmustine; Etoposide; Cyclophosphamide (Cyclo, CY); FTBI
Intervention description: Immunosuppressant administered orally to:
Adults (age 14 and older), beginning on Day -3 with 12 mg loading dose, followed by 4 mg/day.
Children < 13 years or weighing 40 kg, beginning on Day -3 with 3 mg/m² loading dose, followed by 1 mg/ m², rounded to the nearest full milligram.
Daily dosage may be adjusted to maintain a target serum trough level of 3 to 12 ng/ml. Sirolimus dose tapering will begin at Day 100 in the absence of GvHD, with the goal of discontinuation by 6 months.; Immunosuppressant given intravenously (IV) at 15 mg/kg 3 times daily, starting on Day 0 ≥ 2 hr after the completion of the HSCT infusion. Dose of MMF will be based on actual body weight, but limited to 15 kg above ideal body weight. MMF dose tapering will begin at Day 100 in the absence of GvHD, with the goal of discontinuation by 6 months.; For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -6 at the lesser of 15 mg/kg or 550 mg/m².; For Carmustine + Etoposide + Cyclophosphamide cohort, chemotherapy administered IV on Day -4 at 60 mg/kg; Cyclophosphamide is a chemotherapy agent.
For FTBI + Cyclophosphamide cohort, administered IV on Day -3 and -2 at 60 mg/kg.
For Carmustine + Etoposide + Cyclophosphamide cohort, administered IV on Day -2 at 100 mg/kg; For FTBI + Cyclophosphamide cohort, administered as 1320 cGy delivered in 11 120 cGy fractions over 4 days starting on Day -7.
Intervention MeSH terms: Mycophenolic Acid; Sirolimus; Cyclophosphamide; Carmustine; Etoposide; Etoposide phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 2 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      A continuation study of sirolimus and mycophenolate mofetil (MMF) for graft-vs-host disease
      (GvHD) prophylaxis for patients undergoing matched related allogeneic hematopoietic stem cell
      transplantation (HSCT) for acute and chronic leukemia, myelodysplastic syndrome (MDS), high
      risk non-Hodgkin lymphoma (NHL), or Hodgkin lymphoma (HL)
    

Eligibility criteria:

        INCLUSION CRITERIA

          -  Acute myelogenous leukemia (AML), beyond 2nd remission or relapsed/refractory disease,
             age 2 to 60 years

          -  AML, in first or subsequent remission or relapsed/refractory disease, age 51 to 60
             years of age

          -  AML with multilineage dysplasia

          -  Acute lymphoblastic leukemia (ALL), beyond 2nd remission or relapsed/refractory
             disease, age 2 to 60 years

          -  ALL, age 51 - 60 years in first or subsequent remission or relapsed/refractory disease

          -  Chronic myeloid leukemia (CML), beyond 2nd chronic phase or in blast crisis

          -  Myelodysplastic syndrome (MDS), including World Health Organization
             (WHO)classifications of refractory anemia with excess blasts-1 (RAEB-1), RAEB-2 and
             therapy-related MDS

          -  MDS with poor long-term survival including myeloid metaplasia and myelofibrosis

          -  Myeloproliferative disorders

          -  High-risk non-Hodgkin lymphoma (NHL) in 1st emission

          -  Relapsed or refractory NHL

          -  Hodgkin lymphoma (HL) beyond first remission

          -  Males and females of any ethnic background, 2 to 60 years of age

          -  Karnofsky Performance Status (KPS) ≥ 70% or Lansky performance status > 70% for
             patients < 16 years of age.

          -  Related, matched-donor identified [6/6 human leukocyte antigen (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 hematopoietic stem cell transplant (HSCT)

          -  HIV infection

          -  Pregnant

          -  Lactating

          -  Evidence of uncontrolled active infection

          -  Serum creatinine > 1.5 mg/dL or 24-hour creatinine clearance < 50 mL/min

          -  Direct bilirubin, Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >
             2 x upper limit of normal (ULN)

          -  Carbon monoxide diffusing capacity (DlCO) < 60% predicted (adults) OR and in-room air
             oxygen saturation < 92% (children)

          -  Left ventricular ejection fraction < 45% (adults) OR shortening fraction <
             26%(children)

          -  Fasting cholesterol > 300 mg/dL or Triglycerides > 300 mg/dL while on lipid-lowering
             agents.

          -  Receiving investigational drugs unless cleared by the Principal Investigator (PI).

          -  Prior malignancies except basal cell carcinoma or treated carcinoma in-situ.

          -  Cancer treated with curative intent ≤ 5 years (EXCEPTION BY PI DISCRETION) (Cancer
             treated with curative intent > 5 years will be allowed).