Sirolimus, Tacrolimus and Short Course Methotrexate for Prevention of Acute GVHD in Recipients of Mismatched Unrelated Donor Allogeneic Stem Cell Transplantation


Stem Cell Transplantation

Trial Phase

Phase 0

Trial Purpose and Description

Trial Purpose

The primary objective of this trial is to study the safety and efficacy of a novel regimen of sirolimus, tacrolimus and methotrexate as prophylaxis against acute graft versus host disease (GVHD) in recipients of mismatched unrelated donor stem cell grafts. Methotrexate is administered in a low dose format of 5mg/m2 on days +1,3 and 6 only.

Participation Guidelines

16 Years and older

Eligibility Criteria

Inclusion Criteria:

- Patients must have an identified 8/10 or 9/10 matched unrelated donor identified
following a formal search with confirmatory typing through the national marrow donor
program as the best available donor. No matched sibling or fully matched unrelated
donor has been identified. HLA typing of donor and recipient will be performed by
high resolution molecular typing at HLA A, B, C and DRB1/DQ loci. Patients whose best
available donor is matched at 8/10 loci must have at least one of the mismatches at
the DQ locus. (no more than one mismatch at HLA A,B,C,DR allowed).

- Candidates for this trial will meet the following criteria:

1. Adequate organ function for conditioning type:

For patients receiving ablative conditioning

- Left Ventricular ejection fraction >45%

- DLCO >50%

- Creatinine <1.5

- Hepatic enzymes <3x upper limit of normal.

- KPS >70%

For patients receiving non-ablative conditioning:

- KPS >70%

2. Patients with the following diseases will be considered eligible:

- AML in first remission with high risk features (poor risk cytogenetic
abnormalities9, persistent elevated blast count on day +15 or recovery
marrow after induction therapy).

- AML beyond first remission

- ALL in first remission with high risk features (ph+, t4:11)

- ALL beyond first remission

- High risk Myelodysplasia (RAEB-II, RAEB-I with poor-risk cytogenetics)

- Recurrent Aggressive Non-Hodgkins or Hodgkins lymphoma (indolent
histologies excluded) who have failed autologous transplant or have had
inadequate response to salvage therapy.

- CML with transformation

- CLL with transformation or Fludarabine failure.

- Severe aplastic anemia with recurrence or failure after immunosuppressive

Exclusion Criteria:

- Prior allogeneic transplantation

- Active CNS leukemia.

- Female patients who are pregnant or breast feeding

- Karnofsky performance status <70%.

- Active viral, bacterial or fungal infection.

- Patients seropositive for HIV -1,2; HTLV -1,2 (due to the additional immunodeficiency
induced by transplantation and immunosuppressive therapy) Requirement for antifungal
prophylaxis with Voriconazole for the first 30 days is prohibited.

- Patients not providing informed consent.
Stuart Seropian
October 2007
Last Updated:
July 15, 2013
Study HIC#:

Clinicaltrials.gov ID: NCT00612274