Ignite Creation Date:
2025-12-24 @ 11:35 PM
Ignite Modification Date:
2026-01-01 @ 5:21 PM
Study NCT ID:
NCT00686556
Status:
COMPLETED
Last Update Posted:
2017-12-05
First Post:
2008-05-29
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Total Marrow Irradiation for Refractory Acute Leukemia
Sponsor:
Masonic Cancer Center, University of Minnesota
Organization:
Study Overview
Official Title:
Total Marrow Irradiation and Myeloablative Chemotherapy Followed By Double Umbilical Cord BloodTransplantation In Patients With Refractory Acute Leukemia
Status:
COMPLETED
Status Verified Date:
2017-12
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 chemotherapy and total marrow irradiation before a donor umbilical cord blood or hematopoietic stem cell transplant helps stop the growth of cancer cells. It may also 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 cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of total marrow irradiation when given together with combination chemotherapy and umbilical cord blood hematopoietic stem cell transplant in treating patients with acute leukemia, acute myeloid leukemia or multiple myeloma that did not respond to previous therapy.
PURPOSE: This phase I trial is studying the side effects and best dose of total marrow irradiation when given together with combination chemotherapy and umbilical cord blood hematopoietic stem cell transplant in treating patients with acute leukemia, acute myeloid leukemia or multiple myeloma that did not respond to previous therapy.
Detailed Description:
OBJECTIVES:
Primary
* Determine the maximum tolerated dose of total marrow irradiation (TMI) delivered by image-guided tomographic intensity-modulated radiotherapy when administered in combination with myeloablative chemotherapy in patients undergoing double umbilical cord blood (UCB) transplantation or hematopoietic stem cell for refractory acute leukemia.
Secondary
* Determine the incidence of engraftment (defined as achievement of neutrophil count \> 500/uL at 42 days after transplantation).
* Determine the incidence of platelet engraftment at 6 months and at 1 year after transplantation.
* Evaluate the incidence of complete donor chimerism and the relative contribution of each UCB unit to donor engraftment within the first 100 days after transplantation.
* Determine the incidence of transplantation-related mortality (TRM) at 6 months after treatment with a TMI-containing myeloablative conditioning regimen.
* Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at 100 days after transplantation.
* Determine the incidence of chronic GVHD at 1 year after transplantation.
* Determine the incidence of relapse at 1 year after transplantation.
* Determine the survival and disease-free survival at 1 and 2 years after transplantation.
* Assess the durability of remission based on presence of rapid early response (defined by clearance of leukemic blasts from the bone marrow at 21 days after transplantation).
OUTLINE: This is a dose-escalation study of total marrow irradiation (TMI).
* Myeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 1 hour once daily for 3 days between days -12 and -6 and cyclophosphamide IV once daily for 2 days between days -11 and -6. Patients undergo TMI once daily for 4-8 days between days -8 and -1.
* Donor umbilical cord blood (UCB) transplantation: Patients undergo single-unit or double-unit donor UCB transplantation on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously once daily beginning on day 1 and continuing until blood counts recover.
* Related Donor: Related donor bone marrow will be collected (target cell dose 5x10\^8 nucleated cells/kg recipient weight, minimum 3x10\^8 nucleated cells/kg recipient weight) and infused without processing on day 0.
* Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours or orally 2-3 times daily beginning on day -3 and continuing until day 100, followed by a taper until day 180, in the absence of GVHD. Patients also receive mycophenolate mofetil IV or orally 2-3 times daily beginning on day -3 and continuing until day 30 (or 7 days after engraftment), in the absence of acute GVHD.
Patients are followed periodically for up to 2 years after transplantation.
Primary
* Determine the maximum tolerated dose of total marrow irradiation (TMI) delivered by image-guided tomographic intensity-modulated radiotherapy when administered in combination with myeloablative chemotherapy in patients undergoing double umbilical cord blood (UCB) transplantation or hematopoietic stem cell for refractory acute leukemia.
Secondary
* Determine the incidence of engraftment (defined as achievement of neutrophil count \> 500/uL at 42 days after transplantation).
* Determine the incidence of platelet engraftment at 6 months and at 1 year after transplantation.
* Evaluate the incidence of complete donor chimerism and the relative contribution of each UCB unit to donor engraftment within the first 100 days after transplantation.
* Determine the incidence of transplantation-related mortality (TRM) at 6 months after treatment with a TMI-containing myeloablative conditioning regimen.
* Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at 100 days after transplantation.
* Determine the incidence of chronic GVHD at 1 year after transplantation.
* Determine the incidence of relapse at 1 year after transplantation.
* Determine the survival and disease-free survival at 1 and 2 years after transplantation.
* Assess the durability of remission based on presence of rapid early response (defined by clearance of leukemic blasts from the bone marrow at 21 days after transplantation).
OUTLINE: This is a dose-escalation study of total marrow irradiation (TMI).
* Myeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 1 hour once daily for 3 days between days -12 and -6 and cyclophosphamide IV once daily for 2 days between days -11 and -6. Patients undergo TMI once daily for 4-8 days between days -8 and -1.
* Donor umbilical cord blood (UCB) transplantation: Patients undergo single-unit or double-unit donor UCB transplantation on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously once daily beginning on day 1 and continuing until blood counts recover.
* Related Donor: Related donor bone marrow will be collected (target cell dose 5x10\^8 nucleated cells/kg recipient weight, minimum 3x10\^8 nucleated cells/kg recipient weight) and infused without processing on day 0.
* Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours or orally 2-3 times daily beginning on day -3 and continuing until day 100, followed by a taper until day 180, in the absence of GVHD. Patients also receive mycophenolate mofetil IV or orally 2-3 times daily beginning on day -3 and continuing until day 30 (or 7 days after engraftment), in the absence of acute GVHD.
Patients are followed periodically for up to 2 years after transplantation.
Study Oversight
Has Oversight DMC:
True
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?: