NCT00686556

Total Marrow Irradiation for Refractory Acute Leukemia

Total Marrow Irradiation and Myeloablative Chemotherapy Followed By Double Umbilical Cord BloodTransplantation In Patients With Refractory Acute Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: 55 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Acute Lymphoblastic Leukemia
• Myelodysplastic Syndrome
• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	cyclophosphamide	60 mg/kg/day intravenous x 2 days pre-transplant, total dose 120 mg/kg
DRUG	cyclosporine	Beginning on Day -3 pre-transplant maintaining a level of \>200 ng/mL. CSA dosing will be monitored and altered as clinically appropriate by Pharm D or physician, and discontinue at approximately day + 180 post-transplant.
DRUG	Fludarabine	25 mg/m2/day intravenous as a 1 hour infusion for consecutive 3 days pre-transplant, total dose 75 mg/m2
DRUG	mycophenolate mofetil	Beginning on day -3, use intravenous route between days -3 and +5, followed by oral administration on Day +6 through +30, if tolerated. 15mg/kg/dose for patients \<40 kg, 3 gm/day for patients \>40 kg.
RADIATION	total marrow irradiation	Dose escalating schedule per Cohort (TMI: 300 cGy) once daily.
PROCEDURE	umbilical cord blood transplantation	product will be infused via intravenous drip on Day 0 according to current University of Minnesota guidelines for Umbilical Cord Blood Grafts
BIOLOGICAL	Granulocyte colony-stimulating factor	5 mcg/kg/day intravenous or subcutaneous based on body weight beginning on Day +1 after umbilical cord blood infusion until absolute neutrophil count exceeds 2.5 x 10\^9/L for 3 consecutive days.
BIOLOGICAL	HLA-matched related donor bone marrow	Related donor bone marrow or mobilized stem cells 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 according to University of Minnesota Blood and Marrow Transplant Program guidelines.

Timeline

• Start date: 2012-08-01
• Primary completion: 2016-11-01
• Completion: 2016-12-01
• First posted: 2008-05-30
• Last updated: 2017-12-05

Locations

1 site across 1 country: United States