Ignite Creation Date:
2024-05-05 @ 11:40 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00104858
Status:
COMPLETED
Last Update Posted:
2019-07-11
First Post:
2005-03-03
Brief Title:
Fludarabine Phosphate Radiation Therapy and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Sponsor:
Fred Hutchinson Cancer Center
Organization:
Fred Hutchinson Cancer Center
Study Overview
Official Title:
Nonmyeloablative Conditioning With Pre- and Post-Transplant Rituximab Followed by Related or Unrelated Donor Hematopoietic Cell Transplantation for Patients With Advanced Chronic Lymphocytic Leukemia A Multi-Center Trial
Status:
COMPLETED
Status Verified Date:
2019-06
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:
This phase II trial studies how well fludarabine phosphate with radiation therapy and rituximab followed by donor stem cell infusions work in treating patients with high-risk chronic lymphocytic leukemia CLL or small lymphocytic lymphoma SLL with low side effects Nonmyeloablative stem cell transplants use low doses of chemotherapy fludarabine phosphate and radiation to suppress the patients immune system enough to prevent rejection of the donors stem cells Following infusion of donor stem cells a mixture of the patients and the donors stem cells will exist and is called mixed chimerism Donor cells will attack the patients leukemia This is called the graft-versus-leukemia effect Rituximab will be given 3 days before and three times after infusing stem cells to help in controlling CLL early after transplant till the graft-versus-leukemia takes control Further rituximab could augment the graft-versus-leukemia effect by activating donor immune cells and hence improve disease control Sometimes the transplanted cells from a donor can also attack the bodys normal cells Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening
Detailed Description:
PRIMARY OBJECTIVES
I Determine whether nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation HCT improves survival at 18 months for patients with fludarabine fludarabine phosphate-refractory fludarabinecyclophosphamiderituximab FCR-failed or del 17p CLL over that of historical controls 45 at 18 months given CAMPATH-1H alemtuzumab
SECONDARY OBJECTIVES
I Estimate the overall response rate complete remission CR partial remission PR by standard morphologic flow cytometric and molecular techniques
II Assess the rate of relapseprogression
III Define incidences of regimen-related toxicities RRT and infections within the first 100 days and the incidence of transplant-related mortality TRM within the first year
IV Estimate incidences of grade II-III and III-IV acute graft-versus-host disease GVHD and chronic GVHD
V Determine whether the addition of rituximab to the nonmyeloablative conditioning and allogeneic HCT improves survival at 18 months over our historical data 57 at 18 months
VI Determine the incidence of serious adverse events with the addition of rituximab in comparison to historical data of unrelated nonmyeloablative HCT
VII Evaluate the pharmacokinetics of rituximab
VIII Evaluate B-cell and T-cell immune reconstitution in comparison to historical data of unrelated nonmyeloablative HCT
IX Describe donor and host polymorphisms of the FCgammaRIIIa receptor and cluster of differentiation CD32 and evaluate their impact on disease response and relapse
X Investigate the mechanism of disease resistance in relapsednonresponding patients
XI Isolate donor cytotoxic T lymphocytes specific for host minor histocompatibility antigens
OUTLINE
Patients receive a conditioning regimen comprising fludarabine phosphate intravenously IV on days -4 to -2 and rituximab IV on days -3 10 24 and 38
Patients undergo single fraction low-dose total-body irradiation TBI on day 0 After completion of TBI patients undergo allogeneic hematopoietic stem cell transplantation HSCT on day 0 Patients then receive rituximab IV on days 10 24 and 38
Patients receive an immunosuppressive regimen comprising cyclosporine orally PO twice daily BID on days -3 to 56 followed by a taper to day 180 related recipients or on days -3 to 100 followed by a taper to day 180 unrelated recipients Patients also receive mycophenolate mofetil PO BID on days 0-27 related recipients or three times daily TID on days 0-40 followed by a taper to day 96 unrelated recipients
After completion of study treatment patients are followed up at 6 months 1 year 18 months 2 years and then annually thereafter
I Determine whether nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation HCT improves survival at 18 months for patients with fludarabine fludarabine phosphate-refractory fludarabinecyclophosphamiderituximab FCR-failed or del 17p CLL over that of historical controls 45 at 18 months given CAMPATH-1H alemtuzumab
SECONDARY OBJECTIVES
I Estimate the overall response rate complete remission CR partial remission PR by standard morphologic flow cytometric and molecular techniques
II Assess the rate of relapseprogression
III Define incidences of regimen-related toxicities RRT and infections within the first 100 days and the incidence of transplant-related mortality TRM within the first year
IV Estimate incidences of grade II-III and III-IV acute graft-versus-host disease GVHD and chronic GVHD
V Determine whether the addition of rituximab to the nonmyeloablative conditioning and allogeneic HCT improves survival at 18 months over our historical data 57 at 18 months
VI Determine the incidence of serious adverse events with the addition of rituximab in comparison to historical data of unrelated nonmyeloablative HCT
VII Evaluate the pharmacokinetics of rituximab
VIII Evaluate B-cell and T-cell immune reconstitution in comparison to historical data of unrelated nonmyeloablative HCT
IX Describe donor and host polymorphisms of the FCgammaRIIIa receptor and cluster of differentiation CD32 and evaluate their impact on disease response and relapse
X Investigate the mechanism of disease resistance in relapsednonresponding patients
XI Isolate donor cytotoxic T lymphocytes specific for host minor histocompatibility antigens
OUTLINE
Patients receive a conditioning regimen comprising fludarabine phosphate intravenously IV on days -4 to -2 and rituximab IV on days -3 10 24 and 38
Patients undergo single fraction low-dose total-body irradiation TBI on day 0 After completion of TBI patients undergo allogeneic hematopoietic stem cell transplantation HSCT on day 0 Patients then receive rituximab IV on days 10 24 and 38
Patients receive an immunosuppressive regimen comprising cyclosporine orally PO twice daily BID on days -3 to 56 followed by a taper to day 180 related recipients or on days -3 to 100 followed by a taper to day 180 unrelated recipients Patients also receive mycophenolate mofetil PO BID on days 0-27 related recipients or three times daily TID on days 0-40 followed by a taper to day 96 unrelated recipients
After completion of study treatment patients are followed up at 6 months 1 year 18 months 2 years and then annually thereafter
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 |
|---|---|---|---|
| P30CA015704 | NIH | Fred HutchUniversity of Washington Cancer Consortium | httpsreporternihgovquickSearchP30CA015704 |
| NCI-2009-01594 | REGISTRY | None | None |
| 184000 | OTHER | None | None |
| P01CA018029 | NIH | None | None |