Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant For Hematological Cancer
- Conditions
- Chronic Myeloproliferative DisordersGraft Versus Host DiseaseInfectionLeukemiaLymphomaMultiple Myeloma and Plasma Cell NeoplasmMyelodysplastic SyndromesMyelodysplastic/Myeloproliferative NeoplasmsPrecancerous ConditionSecondary Myelofibrosis
- Interventions
- Biological: anti-thymocyte globulinProcedure: allogeneic hematopoietic stem cell transplantationProcedure: hematopoietic stem cell transplantationProcedure: nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantationRadiation: total-body irradiation
- Registration Number
- NCT00589563
- Lead Sponsor
- City of Hope Medical Center
- Brief Summary
RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops 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, antithymocyte globulin, and methotrexate before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well sirolimus, tacrolimus, and antithymocyte globulin work in preventing graft-versus-host disease in patients undergoing a donor stem cell transplant for hematological cancer .
- Detailed Description
OBJECTIVES:
Primary
* To determine the incidence and severity of acute- and chronic-graft-versus-host disease (GVHD) after HLA-matched or -mismatched unrelated donor hematopoietic peripheral blood transplantation in patients with hematologic malignancies scheduled to receive immunosuppressive combination of sirolimus, tacrolimus, and anti-thymocyte globulin as GVHD prophylaxis.
* To determine the safety of this combination in the first six months post-transplant.
Secondary
* To determine the time-to-engraftment, non-relapse mortality rate, overall and disease-free survival, incidence of disease relapse, and incidence of opportunistic infections with this GVHD prophylaxis.
OUTLINE: Patients are stratified according to conditioning regimen (fludarabine phosphate and melphalan vs fractionated total-body irradiation \[FTBI\] and etoposide vs FTBI and cyclophosphamide) and degree of donor/recipient HLA mismatch (high-risk vs low-risk).
* Conditioning regimen: Patients receive 1 of 3 standard conditioning regimens beginning on day -9 or -8 and continuing to day -1 or 0.
* Peripheral blood stem cell transplantation: Patients receive HLA-matched or mismatched unrelated donor peripheral blood stem cells on day 0.
* Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV continuously beginning on day -3 and then orally when tolerated, oral sirolimus on days -3 and -2, anti-thymocyte globulin IV over 4-8 hours on days -3 to 0, and methotrexate\* IV on days 1, 3, and 6. Tacrolimus and sirolimus continue for 3-6 months (with taper).
NOTE: \*Only patients with high-risk HLA mismatch receive treatment with methotrexate.
After completion of study therapy, patients are followed periodically for up to 2 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Fludarabine/Melphalan Conditioning anti-thymocyte globulin Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis Fludarabine/Melphalan Conditioning allogeneic hematopoietic stem cell transplantation Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis Fludarabine/Melphalan Conditioning hematopoietic stem cell transplantation Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis Fludarabine/Melphalan Conditioning nonmyeloablative allogeneic hematopoietic stem cell transplantation Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis Fludarabine/Melphalan Conditioning peripheral blood stem cell transplantation Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis Fludarabine/Melphalan Conditioning total-body irradiation Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Cytoxan Conditioning anti-thymocyte globulin FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Cytoxan Conditioning allogeneic hematopoietic stem cell transplantation FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Cytoxan Conditioning hematopoietic stem cell transplantation FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Cytoxan Conditioning nonmyeloablative allogeneic hematopoietic stem cell transplantation FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Cytoxan Conditioning peripheral blood stem cell transplantation FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Cytoxan Conditioning total-body irradiation FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Etoposide Conditioning anti-thymocyte globulin FTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Etoposide Conditioning allogeneic hematopoietic stem cell transplantation FTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Etoposide Conditioning sirolimus FTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Etoposide Conditioning hematopoietic stem cell transplantation FTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Etoposide Conditioning nonmyeloablative allogeneic hematopoietic stem cell transplantation FTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Etoposide Conditioning peripheral blood stem cell transplantation FTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Etoposide Conditioning total-body irradiation FTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis Fludarabine/Melphalan Conditioning melphalan Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis Fludarabine/Melphalan Conditioning methotrexate Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis Fludarabine/Melphalan Conditioning fludarabine phosphate Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Cytoxan Conditioning cyclophosphamide FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis Fludarabine/Melphalan Conditioning tacrolimus Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis Fludarabine/Melphalan Conditioning sirolimus Fludarabine/Melphalan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Cytoxan Conditioning tacrolimus FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Cytoxan Conditioning methotrexate FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Etoposide Conditioning tacrolimus FTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Cytoxan Conditioning sirolimus FTBI/Cytoxan Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Etoposide Conditioning etoposide FTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis FTBI/Etoposide Conditioning methotrexate FTBI/Etoposide Conditioning with Sirolimus, Tacrolimus and rabbit anti-thymocyte globulin (+/- methotrexate) for GvHD Prophylaxis
- Primary Outcome Measures
Name Time Method Cumulative Incidence of Grade II-IV Acute Graft-Versus-Host Disease (GVHD) at Day 100 100 Days Post Hematopoietic Stem Cell Transplant (HSCT) Patients were evaluated for the development of acute GVHD within the first 100 days post HSCT. The cumulative incidence of grade II-IV acute GVHD was determined using competing risk analysis. Competing risks for acute GVHD were death and nonengraftment.
Severity of Acute GVHD 100 Days Post HSCT All patients were considered for the evaluation of the severity of acute GVHD.
Cumulative Incidence of Chronic GVHD 2 year point estimate was provided. Patients were evaluated for the development of chronic GVHD from 101 days post HSCT to last contact or documented evidence of the disease. The cumulative incidence of chronic GVHD was determined using competing risk analysis. Competing risks for GVHD were death and nonengraftment.
Severity of Chronic GVHD Patients were evaluated until they developed chronic GVHD, a median of 130 days post HSCT All Patients were considered for the evaluation of chronic GVHD severity.
- Secondary Outcome Measures
Name Time Method Time to Absolute Neutrophil Count Recovery (Engraftment) Patients were evaluated until neutrophil recovery, a median of 15 days post HSCT Absolute neutrophil count (ANC) recovery is defined as an ANC of ≥ 0.5 x 10\^9/L (500/mm3) for three consecutive laboratory values obtained on different days
Time to Platelet Count Recovery (Engraftment) Patients were evaluated until platelet recovery, a median of 14 days Platelet recovery is defined as the first date of three consecutive laboratory values ≥ 25 x 10\^9 L obtained on different days.
Occurence of Infections Including Cytomegalovirus and Epstein-Barr Virus Reactivation Median Follow Up: 28 months (Range: 1-49 months) Participants were monitored throughout the trial (median of 28 months) for various infections/complications.
Occurrence of Thrombotic Microangiopathy Median Follow Up: 28 Months (Range: 1-49 months) Participants were monitored throughout the trial (median of 28 months) for various infections/complications. This is the number of participants who developed TMA.
Occurence of Sinusoidal Obstructive Syndrome (SOS) Median Follow Up: 28 Months (Range: 1-49 Months) Participants were monitored throughout the trial (median of 28 months) for various infections/complications. This is the number of participants who developed SOS.
Non-relapse Mortality at 100 Days Post HSCT 100 day point estimate was provided Patients were evaluated for non-relapse mortality (NRM) throughout the study. Non-relapse mortality was considered any death not attributable to relapse or disease progression. The cumulative incidence of NRM was determined using competing risk analysis. Competing risks for NRM were death due to disease progression, relapse and nonengraftment.
Non-relapse Mortality at Two Years Post HSCT 2 year point estimate was provided. Patients were evaluated for non-relapse mortality (NRM) throughout the study. Non-relapse mortality was considered any death not attributable to relapse or disease progression. The cumulative incidence of NRM was determined using competing risk analysis. Competing risks for NRM were death due to disease progression, relapse and nonengraftment.
Overall Survival at Two Years Post HSCT 2 year point estimate was provided. Patients were evaluated for survival (OS) throughout the study. Kaplan Meier estiamtes were calculated for overall survival using time from HSCT to death of any cause or for surviving patients last contact date.
Event Free Survival at Two Years Post HSCT 2 year point estimate was provided. Patients were evaluated for event free survival (EFS) throughout the study. Events were defined as death, relapse, progression, or nonengraftment. Kaplan Meier estimates were calculated as time from HSCT to event.
Incidence of Disease Relapse/Progression at 2 Years Post HSCT 2 year point estimate was provided. Patients were evaluated for relapse/progression post transplant throughout the study. The cumulative incidence of relapse/progression was determined using competing risk analysis. Competing risks for relapse were non-relapse mortality and nonengraftment.
Trial Locations
- Locations (2)
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Banner Good Samaritan Medical Center
🇺🇸Phoenix, Arizona, United States