Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplant
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.
|Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms||Biological: rituximab Drug: busulfan Drug: carmustine Drug: cyclophosphamide Drug: cytarabine Drug: etoposide Drug: fludarabine phosphate Drug: melphalan Radiation: total body irradiation (TBI) Drug: anti-thymocyte globulin IV||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
|Official Title:||A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin®, as Graft-versus-Host- Disease Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation|
- Incidence of Acute Graft-versus-host Disease (GVHD) [ Time Frame: Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria ]
- Severity of Acute Graft-versus-host Disease (GVHD) [ Time Frame: Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria ]
- Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment. [ Time Frame: Within 6 months after PBSCT ]
- Incidence of Chronic GVHD. [ Time Frame: Within 2 years after PBSCT ]
- Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] ) [ Time Frame: post transplant, up to 4 weeks ]
- Overall Survival. [ Time Frame: At 2 years after PBSCT ]
- Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders) [ Time Frame: Within 6 months after PBSCT ]
- Karnofsky Performance Status Performance Status [ Time Frame: 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
|Study Start Date:||May 2008|
|Study Completion Date:||April 2014|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Experimental: Chemotherapy or chemotherapy + total body irradiation
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.
Other Names:Drug: busulfan
Other Names:Drug: carmustine
Other Names:Drug: cyclophosphamide
Other Names:Drug: cytarabine
Other Name: DepocytDrug: etoposide
Other Names:Drug: fludarabine phosphate
Other Name: Fludara®Drug: melphalan
Other Name: AlkeranRadiation: total body irradiation (TBI)
Given once or twice daily
Other Name: radiotherapyDrug: anti-thymocyte globulin IV
Other Name: Thymoglobulin
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00691015
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201-1379|
|Study Chair:||Zaid Al-Kadhimi, MD||Barbara Ann Karmanos Cancer Institute|