Donor Stem Cell Transplant in Treating Patients With Relapsed Hematologic Cancer
- Conditions
- LeukemiaLymphomaMultiple MyelomaPlasma Cell NeoplasmMyelodysplastic SyndromesMyeloproliferative Neoplasms
- Interventions
- Biological: anti-thymocyte globulinBiological: G-CSFProcedure: allogeneic cell transplantation
- Registration Number
- NCT00053196
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or 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 system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving immunosuppressive therapy after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well donor bone marrow or peripheral stem cell transplant works in treating patients with relapsed hematologic cancer after treatment with chemotherapy and autologous stem cell transplant.
- Detailed Description
OBJECTIVES:
* Determine the feasibility of non-myeloablative allogeneic hematopoietic stem cell transplantation by demonstrating that the risk of treatment-related mortality during the first 6 months is an acceptable rate of less than 40% in patients with relapsed hematologic malignancies after prior high-dose chemotherapy and autologous stem cell transplantation.
* Determine the response rates (disease-specific partial and complete response) in patients treated with this regimen.
* Determine the 6-month and 12-month probabilities of response in patients treated with this regimen.
* Determine the distribution of time-to-progression in patients responding to this regimen.
* Determine the percent donor chimerism in patients treated with this regimen.
* Determine the risk of acute and chronic graft-vs-host disease in patients treated with this regimen.
* Determine the toxic effects of this regimen in these patients.
* Determine the disease-free and overall survival of patients treated with this regimen.
OUTLINE: This is an open-label study.
* Preparative Regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours every 6 hours (for a total of 8 doses) on days -4 and -3.
* Graft vs Host Disease (GVHD) Prophylaxis: Patients who have an HLA-identical donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 90 followed by a taper\^\* until day 150 and methotrexate IV on days 1, 3, and 6. Patients with a matched related or matched unrelated donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 180 followed by a taper\^\* as tolerated; methotrexate IV on days 1, 3, 6, and 11; oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper; and rabbit anti-thymocyte globulin IV over 4-6 hours on days -4 to -1 (for a total of 4 doses).
NOTE: \*Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is less than 50% at day 60 or patient has progressive disease
* Allogeneic Stem Cell Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
* Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks.
Patients are followed within 2-3 months, every 3 months for 2 years, and then every 6 months for 3 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 82
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Non myeloblative allogeneic transplant anti-thymocyte globulin Non myeloblative allogeneic hematopoietic cell transplantation after prior autologous transplantation Non myeloblative allogeneic transplant G-CSF Non myeloblative allogeneic hematopoietic cell transplantation after prior autologous transplantation Non myeloblative allogeneic transplant allogeneic cell transplantation Non myeloblative allogeneic hematopoietic cell transplantation after prior autologous transplantation Non myeloblative allogeneic transplant methotrexate Non myeloblative allogeneic hematopoietic cell transplantation after prior autologous transplantation Non myeloblative allogeneic transplant busulfan Non myeloblative allogeneic hematopoietic cell transplantation after prior autologous transplantation Non myeloblative allogeneic transplant mycophenolate mofetil Non myeloblative allogeneic hematopoietic cell transplantation after prior autologous transplantation Non myeloblative allogeneic transplant fludarabine phosphate Non myeloblative allogeneic hematopoietic cell transplantation after prior autologous transplantation Non myeloblative allogeneic transplant tacrolimus Non myeloblative allogeneic hematopoietic cell transplantation after prior autologous transplantation Non myeloblative allogeneic transplant allopurinol Non myeloblative allogeneic hematopoietic cell transplantation after prior autologous transplantation
- Primary Outcome Measures
Name Time Method Treatment-related mortality 6 months post transplant
- Secondary Outcome Measures
Name Time Method Per cent donor chimerism 30, 60, 90, 180 days post transplant Disease-free survival 12 months up to 5 years post study entry Graft-versus-host disease incidence 6 months post transplant Response Rates 6 and 12 months
Trial Locations
- Locations (12)
Union Hospital Cancer Center at Union Hospital
🇺🇸Elkton MD, Maryland, United States
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees
🇺🇸Voorhees, New Jersey, United States
Massey Cancer Center at Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
🇺🇸Columbus, Ohio, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Rebecca and John Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
Beebe Medical Center
🇺🇸Lewes, Delaware, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
St. Francis Hospital
🇺🇸Wilmington, Delaware, United States
Siteman Cancer Center at Barnes-Jewish Hospital
🇺🇸St Louis, Missouri, United States
Wake Forest University Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States