Clinical Trials Directory

Trials / Terminated

TerminatedNCT01116232

Sirolimus, Tacrolimus, Thymoglobulin and Rituximab as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Haploidentical and HLA Partially Matched Donor Hematopoietic Cell Transplantation

A Pilot Phase II Study of Sirolimus, Tacrolimus, Thymoglobulin and Rituximab as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Haploidentical and HLA Partially Matched Donor Hematopoietic Cell Transplantation

Status
Terminated
Phase
Phase 2
Study type
Interventional
Enrollment
4 (actual)
Sponsor
Barbara Ann Karmanos Cancer Institute · Academic / Other
Sex
All
Age
18 Years – 120 Years
Healthy volunteers
Not accepted

Summary

This Phase II clinical trial was designed for patients with hematologic malignancies in need of donor peripheral blood stem cell transplant, and have no HLA matched donor. Therefore It will test the efficacy of combining sirolimus, tacrolimus, antithymocyte globulin, and rituximab in preventing graft versus host disease in transplants from HLA Haploidentical and partially mismatched donors.

Detailed description

OBJECTIVES: Primary * Determine the incidence and severity of acute graft-vs-host disease (GVHD) in patients with hematologic malignancies undergoing donor peripheral blood stem cell transplantation who are receiving sirolimus, tacrolimus, anti-thymocyte globulin, and rituximab as GVHD prophylaxis. * Assess time to engraftment absolute neutrophil count (\> 0.5 x 10\^9/L for 3 consecutive days) and platelet count (\> 20 x 10\^9/L for 3 consecutive days) in these patients. * Determine the safety, as defined by serious adverse events and adverse events related to this immunosuppressive regimen, in the first 6 months after treatment. Secondary * Assess the incidence of chronic GVHD measured within 2 years after transplantation. * Assess overall and disease-free survival at 2 years after transplantation. * Examine the incidence of opportunistic infections including fungal infections, pneumocystis carinii pneumonia, and viral infections (cytomegalovirus, varicella zoster virus, herpes simplex virus, BK virus, Epstein-Barr virus, and post-transplant lymphoproliferative disorder). * Assess the incidence of thrombotic microangiopathy within 100 days of transplantation. * Perform immunocorrelative studies, including T-cell, B-cell, NK-cell, regulatory cell, and allo-reactive T-cell measurement studies via flow cytometry, at 30, 60, 90, and 180 days after transplantation. OUTLINE: Patients receive rituximab IV on days -7 and 3, tacrolimus IV continuously (may switch to orally when the patient is able to eat) and oral sirolimus beginning on day -3, and anti-thymocyte globulin IV over 6 hours on days -3 to -1. Tacrolimus and sirolimus are tapered at the discretion of the treating physician. All patients also receive a standard transplant-preparative regimen and undergo transplantation on day 0. Blood samples are collected before the preparative regimen and at 30, 60, 90, and 180 days after transplantation for correlative immunologic studies. After completion of study treatment, patients are followed up for 2 years.

Conditions

Interventions

TypeNameDescription
BIOLOGICALanti-thymocyte globulinInfuse the first dose over a minimum of 6 hours, and subsequent doses over a minimum of 4 hours via a 0.22 micron in-line filter.
BIOLOGICALrituximabThe total dose chosen for this protocol is 28 mg/kg divided in two doses (14 mg/kg on days -7 and +3). Initial infusion: Start rate of 50 mg/hour; if there is no reaction, increase the rate by 50 mg/hour increments every 30 minutes, to a maximum rate of 400 mg/hour. Subsequent infusions: If patient did not tolerate initial infusion follow initial infusion guidelines. If patient tolerated initial infusion, start at 100 mg/hour; if there is no reaction, increase the rate by 100 mg/hour increments every 30 minutes, to a maximum rate of 400 mg/hour. Note: If a reaction occurs, slow or stop the infusion. If the reaction abates, restart infusion at 50% of the previous rate. In patients who tolerated the Rituximab well in the past, a rapid infusion rate can be used over 90 minutes with 20% of the dose administered in the first 30 minutes and the remaining 80% is given over 60 minutes.
DRUGsirolimusFor adults, Sirolimus will be administered at 12 mg orally loading dose on day -3, followed by 4 mg orally single morning daily dose (target serum level 3-12 ng/ml by HPLC).
DRUGtacrolimusTacrolimus will be administered intravenously at a dose of 0.03 mg/kg (ideal body weight) q 24h by continuous infusion starting on Day -3. Intravenous Tacrolimus will be discontinued once the patient starts eating and the drug will then be given orally at a dose of approximately 4 times the intravenous dose.
OTHERlaboratory biomarker analysislaboratory biomarker analysis
PROCEDUREallogeneic hematopoietic stem cell transplantationallogeneic hematopoietic stem cell transplantation
PROCEDUREmanagement of therapy complicationsmanagement of therapy complications
PROCEDUREperipheral blood stem cell transplantationperipheral blood stem cell transplantation

Timeline

Start date
2010-08-01
Primary completion
2013-05-01
Completion
2013-06-01
First posted
2010-05-04
Last updated
2019-03-26
Results posted
2013-12-13

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT01116232. Inclusion in this directory is not an endorsement.