Ignite Creation Date:
2024-05-05 @ 5:23 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00448201
Status:
COMPLETED
Last Update Posted:
2017-05-30
First Post:
2007-03-14
Brief Title:
Reduced-Intensity Busulfan and Fludarabine With or Without Antithymocyte Globulin Followed by Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease
Sponsor:
UNC Lineberger Comprehensive Cancer Center
Organization:
UNC Lineberger Comprehensive Cancer Center
Study Overview
Official Title:
Allogeneic Hematopoietic Cell Transplantation for Patients With Hematologic Disorders Who Are Ineligible or Inappropriate for Treatment With a More Intensive Therapeutic Regimen
Status:
COMPLETED
Status Verified Date:
2017-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Giving low doses of chemotherapy such as busulfan and fludarabine before a donor stem cell transplant helps stop the growth of cancer and abnormal cells It also helps stop the patients immune system from rejecting the donors stem cells The donated stem cells may replace the patients immune cells and help destroy any remaining cancer or abnormal cells graft-versus-tumor effect Sometimes the transplanted cells from a donor can also make an immune response against the bodys normal cells Immunosuppressive therapy may improve bone marrow function and may be an effective treatment for hematologic cancer or other disease
PURPOSE This clinical trial is studying the side effects and how well giving busulfan and fludarabine with or without antithymocyte globulin followed by donor stem cell transplant works in treating patients with hematologic cancer or other disease
PURPOSE This clinical trial is studying the side effects and how well giving busulfan and fludarabine with or without antithymocyte globulin followed by donor stem cell transplant works in treating patients with hematologic cancer or other disease
Detailed Description:
OBJECTIVES
Primary
Determine the clinical efficacy and toxicity profiles of a nonmyeloablative preparative regimen comprising busulfan and fludarabine with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation in patients with hematologic cancers or other diseases
Determine the feasibility of this regimen in these patients
Establish a treatment-related mortality during the first 6 months that is less than 20 in patients treated with this regimen
Secondary
Determine the response rates disease-specific partial response and complete response in patients treated with this regimen
Determine overall and progression-free survival of patients treated with this regimen
Determine the percent donor chimerism and immunologic recovery including dendritic cell recovery in patients treated with this regimen
Determine the risk of acute and chronic graft-versus-host disease and other toxicities in patients treated with this regimen
Assess the overall nonhematologic grades 3 and 4 toxicity of this regimen including the incidence of veno-occlusive disease and pulmonary toxicity in these patients
OUTLINE Patients are assigned to 1 of 4 treatment groups according to disease type and donor type
Preparative regimen
Group 1 patients with acute myeloid leukemia AML acute lymphoblastic leukemia ALL IPSS International Prognostic Scoring System score high-risk myelodysplastic syndromes HR MDS or chronic myelogenous leukemia CML with an human leukocyte antigen HLA-matched related donor MRD Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and busulfan IV continuously over 48 hours on days -6 and -5
Group 2 patients with AML ALL IPSS HR MDS or CML with an HLA-matched unrelated donor MUD or mismatched related donor MMRD Patients receive fludarabine phosphate and busulfan as in group 1 and anti-thymocyte globulin IV over 4 hours on day -8
Group 3 patients with all other diseases with a MRD Patients receive fludarabine phosphate and busulfan as in group 1 and anti-thymocyte globulin as in group 2
Group 4 patients with all other disease with a MUD or MMRD Patients receive fludarabine phosphate and busulfan as in group 1 and anti-thymocyte globulin IV over 4 hours on days -8 and -7
Allogeneic stem cell transplantation All patients undergo allogeneic peripheral blood stem cell transplantation on day 0 Patients then receive sargramostim GM-CSF subcutaneously once daily beginning on day 5 groups 1 and 2 or day 7 groups 3 and 4 and continuing until blood counts recover
Graft-vs-host disease GVHD prophylaxis All patients receive oral tacrolimus twice daily on days -1 to 120 followed by a taper until day 180 Patients in groups 1 and 2 also receive methotrexate IV on days 1 3 and 6
Donor lymphocyte infusion DLI After day 120 patients with progressive disease or stable disease while off immunosuppression and with no evidence of active GVHD may receive DLI Treatment with DLI may repeat every 8 weeks for up to 3 total infusions in the absence of disease response or GVHD
Peripheral blood andor bone marrow samples are collected at baseline and then at 30 60 90 120 and 180 days post-transplantation Chimerism including the following subsets whole blood T-cells as defined by cluster of differentiation 3 CD3 positivity B-cells as defined by Cluster of Differentiation 19 CD19 positivity and myeloid cells as defined by Cluster of Differentiation 14 CD14 and Cluster of Differentiation 15 CD15 positivity is analyzed by polymerase chain reaction technology
After restaging between Days 90 and 100 and between Days 150 to 180 patients are followed every 6 months for 1 years and then yearly for a maximum of 5 years from study entry
Primary
Determine the clinical efficacy and toxicity profiles of a nonmyeloablative preparative regimen comprising busulfan and fludarabine with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation in patients with hematologic cancers or other diseases
Determine the feasibility of this regimen in these patients
Establish a treatment-related mortality during the first 6 months that is less than 20 in patients treated with this regimen
Secondary
Determine the response rates disease-specific partial response and complete response in patients treated with this regimen
Determine overall and progression-free survival of patients treated with this regimen
Determine the percent donor chimerism and immunologic recovery including dendritic cell recovery in patients treated with this regimen
Determine the risk of acute and chronic graft-versus-host disease and other toxicities in patients treated with this regimen
Assess the overall nonhematologic grades 3 and 4 toxicity of this regimen including the incidence of veno-occlusive disease and pulmonary toxicity in these patients
OUTLINE Patients are assigned to 1 of 4 treatment groups according to disease type and donor type
Preparative regimen
Group 1 patients with acute myeloid leukemia AML acute lymphoblastic leukemia ALL IPSS International Prognostic Scoring System score high-risk myelodysplastic syndromes HR MDS or chronic myelogenous leukemia CML with an human leukocyte antigen HLA-matched related donor MRD Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and busulfan IV continuously over 48 hours on days -6 and -5
Group 2 patients with AML ALL IPSS HR MDS or CML with an HLA-matched unrelated donor MUD or mismatched related donor MMRD Patients receive fludarabine phosphate and busulfan as in group 1 and anti-thymocyte globulin IV over 4 hours on day -8
Group 3 patients with all other diseases with a MRD Patients receive fludarabine phosphate and busulfan as in group 1 and anti-thymocyte globulin as in group 2
Group 4 patients with all other disease with a MUD or MMRD Patients receive fludarabine phosphate and busulfan as in group 1 and anti-thymocyte globulin IV over 4 hours on days -8 and -7
Allogeneic stem cell transplantation All patients undergo allogeneic peripheral blood stem cell transplantation on day 0 Patients then receive sargramostim GM-CSF subcutaneously once daily beginning on day 5 groups 1 and 2 or day 7 groups 3 and 4 and continuing until blood counts recover
Graft-vs-host disease GVHD prophylaxis All patients receive oral tacrolimus twice daily on days -1 to 120 followed by a taper until day 180 Patients in groups 1 and 2 also receive methotrexate IV on days 1 3 and 6
Donor lymphocyte infusion DLI After day 120 patients with progressive disease or stable disease while off immunosuppression and with no evidence of active GVHD may receive DLI Treatment with DLI may repeat every 8 weeks for up to 3 total infusions in the absence of disease response or GVHD
Peripheral blood andor bone marrow samples are collected at baseline and then at 30 60 90 120 and 180 days post-transplantation Chimerism including the following subsets whole blood T-cells as defined by cluster of differentiation 3 CD3 positivity B-cells as defined by Cluster of Differentiation 19 CD19 positivity and myeloid cells as defined by Cluster of Differentiation 14 CD14 and Cluster of Differentiation 15 CD15 positivity is analyzed by polymerase chain reaction technology
After restaging between Days 90 and 100 and between Days 150 to 180 patients are followed every 6 months for 1 years and then yearly for a maximum of 5 years from study entry
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P30CA016086 | NIH | None | httpsreporternihgovquickSearchP30CA016086 |