Graft-Versus-Host Disease (GVHD) Prophylaxis After Allogeneic Peripheral Blood Hematopoietic Cell Transplantation

• ClinicalTrials.gov Identifier: NCT00803010
• Recruitment Status: Completed
• First Posted: December 5, 2008
• Results First Posted: May 5, 2014
• Last Update Posted: July 31, 2015
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Study Description

Brief Summary:

The purpose of this research is to compare the effectiveness of Tacrolimus and Rapamycin to Tacrolimus and Methotrexate in the prevention of severe graft-versus-host-disease. Graft-versus-host-disease (GVHD) is a risk associated with allogeneic hematopoietic cell transplants (HCT). An allogeneic hematopoietic cell transplant is a transplant using bone marrow and blood cells that come from someone other than the patient (a donor).

Condition or disease	Intervention/treatment	Phase
Acute Graft Versus Host Disease	Drug: Tacrolimus (TAC); Drug: Methotrexate (MTX); Drug: Rapamycin (RAPA)	Phase 2

Detailed Description:

All drugs used in this study have been used in the prevention of graft-versus-host-disease after allogeneic hematopoietic cell transplant. Tacrolimus and Methotrexate used in combination are currently used as standard of care in the prevention of graft-versus-host-disease after allogeneic hematopoietic cell transplant. Tacrolimus and Rapamycin is a newer combination we are testing to see if it would be better than Tacrolimus and Methotrexate.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 74 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Phase II Trial of Tacrolimus and Rapamycin vs. Tacrolimus and Methotrexate as GVHD Prophylaxis After Allogeneic Peripheral Blood Hematopoietic Cell Transplantation
• Study Start Date: September 2008
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Tacrolimus / Rapamycin (TAC/RAPA); Tacrolimus: beginning 3 days before transplant and given for at least 50 days. Rapamycin: given the day before transplant and continued daily for at least one year.	Drug: Tacrolimus (TAC); Tacrolimus: administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3.; Other Names: FK-506; fujimycin; Prograf; Advagraf; Protopic; Drug: Rapamycin (RAPA); Rapamycin: initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily.; Other Name: Sirolimus
Active Comparator: Tacrolimus / Methotrexate (TAC/MTX); Tacrolimus: beginning 3 days before transplant and given for at least 50 days. Methotrexate: given on days 1, 3, 6 and 11, after transplant.	Drug: Tacrolimus (TAC); Tacrolimus: administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3.; Other Names: FK-506; fujimycin; Prograf; Advagraf; Protopic; Drug: Methotrexate (MTX); Methotrexate: administered on day 1 at dose of 15 mg/m^2, and a dose of 10 mg/m^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance.; Other Names: Trexall; Rheumatrex

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Evidence of Acute Graft Versus Host Disease (aGVHD), Post Transplant [ Time Frame: 100 Days Post Transplant ]

   Incidence of acute graft versus host disease grades 2-3 according to the Common Toxicity Criteria (CTC) version 3.

   Graft-versus-host-disease (GVHD) is a risk associated with allogeneic hematopoietic cell transplants (HCT). Clinical evidence of acute GVHD was recorded per standard grading scheme.

   Acute GVHD classified as the following:

   1. classic acute GVHD - onset within 100 days after transplant
   2. persistent - acute GVHD with onset prior to day 100 and without resolution beyond day 100
   3. recurrent - acute GVHD recurrent after prior episode of acute GVHD
   4. late acute GVHD - syndrome consistent with acute GVHD, without features of chronic GVHD, with onset occurring beyond 100 days

Secondary Outcome Measures :

1. Incidence of Increased Absolute Numbers of Regulatory T Cells (Treg) [ Time Frame: 30 days and 90 days ]
   Absolute numbers of Treg at designated time points according to study arm. MTX = methotrexate/tacrolimus-treated patients; SIR = sirolimus/tacrolimus-treated patients; Treg absolute number units = number of cells/microL. A two-sided Wilcoxon's rank-sum test was employed to test differences in percent Treg (% Treg/total CD4+ cells).
2. 2 Year Post Transplant Overall Survival (OS) Rate [ Time Frame: 2 years ]
   Defined as time from transplantation (day 0 as day of stem cell infusion per standard nomenclature) to death from any cause .

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥ 16 and ≤ 70
• Signed informed consent
• Adequate vital organ function
• No active infection, or asymptomatic infection well controlled by antibiotic HIV negative by ELISA or RT-PCR [if ELISA is positive and RT-PCR is negative, the ELISA is considered false positive]
• Hepatitis B and C negative by serology or RT-PCR
• Performance status: Karnofsky Performance Status Score ≥ 60%.

Exclusion Criteria:

• Those with any Sorror's co-morbidity factors with score > 3
• 2 or more Sorror's factors with composite score of ≥ 3

Contacts and Locations

Locations

United States, Florida

H.Lee Moffitt Cancer Center

Tampa, Florida, United States, 33612

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Investigators

• Study Director: Claudio Anasetti, MD; HLeeMoffittCancerCenter

More Information

Additional Information:

H.Lee Moffitt Cancer Center & Research Institute 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pidala J, Kim J, Jim H, Kharfan-Dabaja MA, Nishihori T, Fernandez HF, Tomblyn M, Perez L, Perkins J, Xu M, Janssen WE, Veerapathran A, Betts BC, Locke FL, Ayala E, Field T, Ochoa L, Alsina M, Anasetti C. A randomized phase II study to evaluate tacrolimus in combination with sirolimus or methotrexate after allogeneic hematopoietic cell transplantation. Haematologica. 2012 Dec;97(12):1882-9. doi: 10.3324/haematol.2012.067140. Epub 2012 Jun 11.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT00803010
• Other Study ID Numbers: MCC-15372; IRB 106591
• First Posted: December 5, 2008
• Results First Posted: May 5, 2014
• Last Update Posted: July 31, 2015
• Last Verified: December 2013

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:

Acute Graft Versus Host Disease (aGVHD); GVHD; graft-versus-host disease; tacrolimus; sirolimus; methotrexate; combination therapy; GVHD prophylaxis

Additional relevant MeSH terms:

Graft vs Host Disease; Immune System Diseases; Sirolimus; Methotrexate; Tacrolimus; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; 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; Calcineurin Inhibitors; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antifungal Agents