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

November 29, 2016 updated by: Yale University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
sirolimus, tacrolimus and short course methotrexate
Drug: tacrolimus
Tacrolimus will be administered at a dose of .02mg/kg/d IVCI beginning day -3 until able to take oral medicines reliably. Blood levels will be maintained at 5-10 ng/ml. The oral dose will be 4 times the IV dose. Tacrolimus will be converted to oral dosing prior to hospital discharge. Tacrolimus will be continued until 4 months post transplant (day +120) unless toxicity, refractory GVHD or the development of disease recurrence mandate discontinuation of the drug.
Other Names:
  • FK506
  • Prograf(TM)
Drug: Sirolimus
Sirolimus will be administered as a 12 mg oral loading dose on day -3 followed by 4mg daily. Sirolimus levels will be obtained on day +0 and then at least twice weekly to maintain a trough serum level of 3-12 ng/ml. Sirolimus will be continued until 5 months post transplant (day +150) unless toxicity, refractory GVHD or the development of disease recurrence mandate discontinuation of the drug.
Other Names:
  • Rapamune
Drug: Methotrexate
Methotrexate, dose #1 will be administered on day +1 post transplantation, as an IV bolus, provided at least 24 hours have elapsed following infusion of donor stem cells at a dose of 10mg/m2. Dose #2 of Methotrexate will be administered 48 hours later, as IV bolus on day +3 at a dose of 5mg/m2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety/Efficacy of a novel regimen of sirolimus, tacrolimus and methotrexate
Time Frame: Upon completion of study
Upon completion of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Investigators

  • Principal Investigator: Stuart Seropian, M.D., Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

January 29, 2008

First Submitted That Met QC Criteria

February 8, 2008

First Posted (Estimate)

February 11, 2008

Study Record Updates

Last Update Posted (Estimate)

November 30, 2016

Last Update Submitted That Met QC Criteria

November 29, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0703002455

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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