Donor Stem Cell Transplant in Treating Patients With Relapsed Hematologic Cancer
|ClinicalTrials.gov Identifier: NCT00053196|
Recruitment Status : Completed
First Posted : January 28, 2003
Last Update Posted : July 1, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Lymphoma Multiple Myeloma Plasma Cell Neoplasm Myelodysplastic Syndromes Myeloproliferative Neoplasms||Biological: anti-thymocyte globulin Biological: G-CSF Drug: busulfan Drug: fludarabine phosphate Drug: methotrexate Drug: mycophenolate mofetil Drug: tacrolimus Procedure: allogeneic cell transplantation Drug: allopurinol||Phase 2|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||82 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation For Patients With Disease Relapse Or Myelodysplasia After Prior Autologous Transplantation|
|Study Start Date :||December 2002|
|Actual Primary Completion Date :||November 2006|
|Actual Study Completion Date :||August 2010|
Experimental: Non myeloblative allogeneic transplant
Non myeloblative allogeneic hematopoietic cell transplantation after prior autologous transplantation
Biological: anti-thymocyte globulin
2.5mg/kg/day IV infusion over 6 hrs x 4 doses Days -4 to -1 (for MUD and 9/10 related donor transplants only)Biological: G-CSF
5 ug/kg/day subQ injection Day 7 until ANC> 1000/uL for 3 consec days
Other Name: filgrastimDrug: busulfan
0.8mg/kg IV infusion over 2 hrs q 6 hrs x 8 doses Days -4 thru -3Drug: fludarabine phosphate
30 mg/sq m/day IVBP over 30 min Days -7 thru -3Drug: methotrexate
5 mg/sq m/day IV infusion Days 1, 3, & 6 for HLA-identical donor transplants and Days 1, 3, 6, & 11 for MUD & 9/10 related donor transplantsDrug: mycophenolate mofetil
15mg/kg PO bid Day -2 to Day 60, then taper as tolerated (for MUD and 9/10 related donor transplants only)Drug: tacrolimus
target serum level is 5-10 ng/mL. Start with 0.03mg/kg PO bid Day -1 to Day 90, then taper thru Day 150 for HLA identical donor transplants and Day -1 to Day 180 then taper for MUD and 9/10 related donor transplantsProcedure: allogeneic cell transplantation
2,000,000-8,000,000 CD34+ cells total via infusion Days 0 and 1Drug: allopurinol
300 mg/day PO Days -8 thru -1
- Treatment-related mortality [ Time Frame: 6 months post transplant ]
- Per cent donor chimerism [ Time Frame: 30, 60, 90, 180 days post transplant ]
- Disease-free survival [ Time Frame: 12 months up to 5 years post study entry ]
- Graft-versus-host disease incidence [ Time Frame: 6 months post transplant ]
- Response Rates [ Time Frame: 6 and 12 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00053196
|United States, California|
|Rebecca and John Moores UCSD Cancer Center|
|La Jolla, California, United States, 92093-0658|
|United States, Delaware|
|Beebe Medical Center|
|Lewes, Delaware, United States, 19958|
|CCOP - Christiana Care Health Services|
|Newark, Delaware, United States, 19713|
|St. Francis Hospital|
|Wilmington, Delaware, United States, 19805|
|United States, Maryland|
|Union Hospital Cancer Center at Union Hospital|
|Elkton MD, Maryland, United States, 21921|
|United States, Missouri|
|Siteman Cancer Center at Barnes-Jewish Hospital|
|St Louis, Missouri, United States, 63110|
|United States, New Jersey|
|Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees|
|Voorhees, New Jersey, United States, 08043|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263-0001|
|United States, North Carolina|
|Wake Forest University Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157-1096|
|United States, Ohio|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University|
|Columbus, Ohio, United States, 43210-1240|
|United States, Pennsylvania|
|Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital|
|Pittsburgh, Pennsylvania, United States, 15224-1791|
|United States, Virginia|
|Massey Cancer Center at Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298-0037|
|Study Chair:||Asad Bashey, MD, PhD||University of California, San Diego|