Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplant
- Conditions
- Myelodysplastic/Myeloproliferative NeoplasmsLeukemiaLymphomaMultiple Myeloma and Plasma Cell NeoplasmChronic Myeloproliferative DisordersMyelodysplastic Syndromes
- Interventions
- Biological: rituximabRadiation: total body irradiation (TBI)Drug: anti-thymocyte globulin IV
- Registration Number
- NCT00691015
- Lead Sponsor
- Barbara Ann Karmanos Cancer Institute
- Brief Summary
RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus, and antithymocyte globulin before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying the side effects of giving sirolimus together with tacrolimus and antithymocyte globulin and to see how well it works in preventing graft-versus-host disease in patients with hematologic cancer who are undergoing donor stem cell transplant.
- Detailed Description
OBJECTIVES:
Primary
* To determine the incidence and severity of acute graft-versus-host disease (GVHD) after HLA-matched or -mismatched unrelated donor peripheral blood stem cell transplantation (PBSCT) in patients with hematologic malignancies treated with immunosuppressive therapy comprising sirolimus, tacrolimus, and anti-thymocyte globulin as GVHD prophylaxis.
* To determine the safety of this regimen in these patients at 6 months after PBSCT.
Secondary
* To determine the time to engraftment (i.e., platelet and absolute neutrophil recovery) in patients treated with this regimen.
* To determine the length of hospital stay of these patients within 100 days after PBSCT.
* To determine the incidence of infections, including CMV and EBV reactivation and post-transplant lymphoproliferative disorders, in patients treated with this regimen.
* To determine the incidence of thrombotic microangiopathy and veno-occlusive disease in patients treated with this regimen.
* To determine the incidence of chronic GVHD in patients treated with this regimen.
* To determine the overall and disease-free survival of these patients at 2 years after PBSCT.
* To determine the Karnofsky performance status of these patients at baseline and at various time points after PBSCT.
* To conduct immunocorrelative studies prior to and at various time points after PBSCT.
OUTLINE:
* Conditioning regimen: Patients receive 1 of 6 conditioning regimens (standard of care treatment) between days -9 and -3, based on diagnosis and the treating physician's preference regarding regimen intensity.
* Regimen I: Patients receive fludarabine phosphate IV and busulfan IV.
* Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV.
* Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV.
* Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV.
* Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV.
* Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI.
* Allogeneic peripheral blood stem cell transplantation: Patients undergo filgrastim (G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0.
* Graft-versus-host disease prophylaxis (GVHD): Patients receive tacrolimus IV continuously over 24 hours or orally and sirolimus orally beginning on day -3 and continuing until day 30 or day 90, followed by a taper in the absence of GVHD. Patients also receive anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.
Blood samples are obtained at baseline and periodically during study for correlative biomarker studies. Samples are analyzed by T-cell immunophenotyping, absolute subset number quantification, and multi-parameter flow cytometry for evaluation of immune reconstitution, T-cell differentiation status, NK-cell recovery, allo-reactivity of donor T-cells after transplantation, and regulatory T-cell reconstitution.
After completion of study therapy, patients are followed periodically for up to 2 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Chemotherapy or chemotherapy + total body irradiation rituximab Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV. Chemotherapy or chemotherapy + total body irradiation etoposide Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV. Chemotherapy or chemotherapy + total body irradiation carmustine Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV. Chemotherapy or chemotherapy + total body irradiation anti-thymocyte globulin IV Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV. Chemotherapy or chemotherapy + total body irradiation total body irradiation (TBI) Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV. Chemotherapy or chemotherapy + total body irradiation busulfan Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV. Chemotherapy or chemotherapy + total body irradiation melphalan Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV. Chemotherapy or chemotherapy + total body irradiation cyclophosphamide Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV. Chemotherapy or chemotherapy + total body irradiation cytarabine Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV. Chemotherapy or chemotherapy + total body irradiation fludarabine phosphate Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens: Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV. Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV. Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV. Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV. Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV.
- Primary Outcome Measures
Name Time Method Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment. Within 6 months after PBSCT Incidence of Acute Graft-versus-host Disease (GVHD) Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria Severity of Acute Graft-versus-host Disease (GVHD) Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria
- Secondary Outcome Measures
Name Time Method Overall Survival. At 2 years after PBSCT Incidence of Chronic GVHD. Within 2 years after PBSCT Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] ) post transplant, up to 4 weeks Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders) Within 6 months after PBSCT Karnofsky Performance Status Performance Status At 90 days after PBSCT 100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of their personal needs.
50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent.
20 - Very sick; hospital admission necessary; active supportive treatment necessary.
10 - Moribund; fatal processes progressing rapidly. 0 - Dead
Trial Locations
- Locations (1)
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States