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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by Yale University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Yale University
ClinicalTrials.gov Identifier:
NCT00612274
First received: January 29, 2008
Last updated: June 5, 2009
Last verified: June 2009
History of Changes
  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.


Condition Intervention Phase
Stem Cell Transplantation
 Drug: tacrolimus
Drug: Sirolimus
Drug: Methotrexate
 Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Yale University:

Primary Outcome Measures:
  • Safety/Efficacy of a novel regimen of sirolimus, tacrolimus and methotrexate [ Time Frame: Upon completion of study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: October 2007
Estimated Study Completion Date: October 2010
Estimated Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00612274

Contacts
Contact: Noelle Sowers, RN 203-785-2442 noelle.sowers@yale.edu
Contact: Donna LaCivita, MPH 203-737-2579 donna.lacivita@yale.edu

Locations
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06520
Contact: Noelle Sowers, RN     203-785-2442     noelle.sowers@yale.edu    
Principal Investigator: Stuart Seropian, M.D.            
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Stuart Seropian, M.D. Yale University
  More Information

No publications provided

Responsible Party: Stuart Seropian, M.D., Yale University
ClinicalTrials.gov Identifier: NCT00612274     History of Changes
Other Study ID Numbers: 0703002455
Study First Received: January 29, 2008
Last Updated: June 5, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
allogeneic

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Methotrexate
Sirolimus
Everolimus
Tacrolimus
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
 Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Antibiotics, Antineoplastic
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on May 21, 2013