Leukemia, Lymphoma, Non-Hodgkin, Hematologic Diseases, Acute GVHD
Conditions
Brief summary
GVHD prophylaxis of sirolimus and mycophenolate mofetil for patients undergoing matched related allogeneic transplant for acute and chronic leukemia, MDS, high risk NHL and HL
Detailed description
To explore the novel combination of sirolimus and mycophenolate mofetil (MMF) as graft versus host disease (GVHD) prevention in HLA matched related donor blood or marrow transplantation (BMT). This study will report the toxicities associated with this drug combination and also explore possible correlations between specific blood cell types and antibody production during this therapy.
Interventions
DRUGSirolimus
Immunosuppressant beginning day -3 with 12 mg oral loading dose, 4 mg/day orally for adults
DRUGMMF
Immunosuppressant given through IV on day 0 at 15 mg/kg twice daily ≥ 2hr after the completion for the donor cell infusion
DRUGBCNU
15 mg/kg, IV
DRUGVP-16
60 mg/kg, IV
DRUGCY
For subjects aged 18-60 with lymphoma 100 mg/kg, IV For subjects aged with AML, ALL or CML 18-50 60 mg/kg, IV For subjects aged 51-60 with MDS, AML or ALL or patients age 18-60 with MDS, secondary AML or non-CML myeloproliferative disease 45 mg/kg
DRUGFTBI
1320 cGy delivered in 11 120 cGy fractions over 4 day
DRUGBU
BU 1 mg/kg every 6hr x 4 doses, IV
Sponsors
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the incidence of grade II-IV acute GVHD with sirolimus and mycophenolate mofetil GVHD prophylaxis. | D+100 post-transplant |
Countries
United States
Outcome results
None listed