Combination Chemotherapy, Donor Stem Cell Transplant, Tacrolimus, Mycophenolate Mofetil, and Cyclophosphamide in Treating Patients With Hematologic Cancer
- Conditions
- LymphomaLeukemiaMyelodysplastic Syndromes
- Interventions
- Procedure: allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantation
- Registration Number
- NCT00782379
- Lead Sponsor
- Northside Hospital, Inc.
- Brief Summary
RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving high-dose cyclophosphamide together with tacrolimus and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well combination chemotherapy works when given together with a donor stem cell transplant, followed by tacrolimus, mycophenolate mofetil, and high-dose cyclophosphamide, in treating patients with high-risk hematologic cancer.
- Detailed Description
OBJECTIVES:
Primary
* To estimate the incidence of graft rejection and severe graft-versus-host disease after myeloablative HLA-mismatched peripheral blood stem cell transplantation (PBSCT) from first-degree relatives in patients with high-risk hematologic malignancies.
Secondary
* To estimate overall survival, relapse, non-relapse mortality, and event-free survival in these patients.
* To characterize additional hematologic and non-hematologic toxicities of myeloablative haploidentical PBSCT.
* To characterize donor hematopoietic chimerism in peripheral blood stem cells after PBSCT.
OUTLINE:
* Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -2, busulfan IV over 3 hours on days -7 to -4, and cyclophosphamide IV over 1-2 hours on days -3 and -2.
* Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo infusion of unmanipulated peripheral blood stem cells on day 0.
* Post-transplant regimen: Patients receive high-dose cyclophosphamide IV over 1-2 hours on days 3 and 4, tacrolimus IV over 24 hours or orally twice daily on days 5-180, and oral mycophenolate mofetil 3 times daily on days 5-34 followed by a taper to day 90. Treatment continues in the absence of disease progression or clinically significant graft-vs-host disease.
After completion of PBSCT, patients are followed periodically for 1 year.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Myeloablative Haploidentical Transplant allogeneic hematopoietic stem cell transplantation All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide. Myeloablative Haploidentical Transplant peripheral blood stem cell transplantation All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide. Myeloablative Haploidentical Transplant busulfan All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide. Myeloablative Haploidentical Transplant cyclophosphamide All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide. Myeloablative Haploidentical Transplant tacrolimus All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide. Myeloablative Haploidentical Transplant fludarabine phosphate All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide. Myeloablative Haploidentical Transplant mycophenolate mofetil All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide.
- Primary Outcome Measures
Name Time Method Incidence of Graft Rejection for Patients at Day 100 Day 100 Number of patients who experienced graft rejection by Day 100
Number of Patients Who Experienced Severe Graft-versus-host Disease (GVHD)(Grade 3 or 4) Day 100 Number of patients who experienced post-transplant complication (GVHD) as seen by clinical evidence
- Secondary Outcome Measures
Name Time Method Overall Survival at Day 100 Day 100 Overall survival is assessed, without regard to disease status, post-transplant, at Day 100.
Non-relapse Mortality at 1 Year After Peripheral Blood Stem Cell Transplantation (PBSCT) 1 year Non-relapse mortality refers to whether a patient dies of causes related to something other than the primary disease.
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 30 Post-transplantation Day 30 Chimerism analysis of peripheral blood mononuclear cells using PCR (polymerase chain reaction) for STR/VNTR (short tandme repeat/variable number tandem repeat) will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Non-relapse Mortality at Day 100 After Peripheral Blood Stem Cell Transplantation (PBSCT) Day 100 Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 60 Post-transplantation Day 60 Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Achievement of >90% (Full) Donor Chimerism in the T-Cell Lineage as Measured by PCR at Day 90 Post-transplantation Day 90 Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Overall Survival at 12 Months 12 months Overall survival, defined as a patient being alive after transplant, is without regard to disease status.
Disease Free Survival at 12 Months 12 months Disease free survival refers to patients with no evidence of disease after transplant, at the 12 month time point.
Disease Free Survival at Day 100 Day 100 Disease free survival refers to patients with no evidence of disease after transplant, at the Day 100 time point.
Trial Locations
- Locations (1)
Blood and Marrow Transplant Group of Georgia
🇺🇸Atlanta, Georgia, United States