Clinical trial NCT00612274: Sirolimus, Tacrolimus and Short Course Methotrexate for Prevention of Acute GVHD in Recipients of Mismatched Unrelated Donor Allogeneic Stem Cell Transplantation
Official title: Pilot Study of Sirolimus, Tacrolimus and Short Course Methotrexate for Prevention of Acute Graft Versus Host Disease in Recipients of Mismatched Unrelated Donor Allogeneic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Stem Cell Transplantation
Keywords: allogeneic
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2008-02-11
Enrollment: 26
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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 therapy.

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.

Primary outcomes:
measure: Safety/Efficacy of a novel regimen of sirolimus, tacrolimus and methotrexate
timeFrame: Upon completion of study
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
Study officials:
affiliation: Yale University
name: Stuart Seropian, M.D.
role: PRINCIPAL_INVESTIGATOR
References: