Clofarabine and Low Dose Total Body Irradiation as a Preparative Regimen for Stem Cell Transplant in Leukemia.
- Conditions
- Leukemia Lymphoblastic, AcuteAcute Myeloid LeukemiaNeoplasm Recurrent
- Interventions
- Radiation: Total Body IrradiationOther: Stem Cell Transplantation
- Registration Number
- NCT01041508
- Lead Sponsor
- Therapeutic Advances in Childhood Leukemia Consortium
- Brief Summary
Stem cell transplant is an important therapeutic option for pediatric patients with relapsed or refractory leukemia. Although, full myeloablative transplants are widely used for patients with acute leukemia, myeloablative chemo-radiotherapy may not be feasible in some specific settings. These settings include 1) patients with pre-existing health issues and organ toxicities; 2) patients who have relapsed post-ablative transplant and need a second stem cell transplant; and 3) leukemia patients with advanced disease who have been heavily pre-treated. Clofarabine, a new purine nucleoside anti-metabolite, has the advantage of significant antileukemic activity in addition to its possible immuno-suppressive properties. In this study we plan to determine the maximum feasible dose (MFD) of Clofarabine in combination with total body irradiation that can achieve durable donor engraftment without causing excessive toxicity.
- Detailed Description
Standard non-myeloablative regimens use Fludarabine and low dose total body irradiation (TBI) as pioneered by the Seattle group. Fludarabine is mainly used for its immuno-suppressive properties and has limited anti-leukemic effects. Since, the non-myeloablative and RIC regimens do not include intensive chemotherapy; relapse rates can be higher in RIC regimens compared to full myeloablative regimens. One way to improve overall survival in non-myeloablative / RIC setting is to add more effective anti-leukemia agents to prevent post-transplant relapses, without increasing TRM. Clofarabine, a new purine nucleoside anti-metabolite, has the advantage of significant antileukemic activity in addition to its possible immuno-suppressive properties. Combining Clofarabine with low dose TBI as a non-myeloablative preparative regimen may improve overall outcomes of SCT in advanced hematological malignancies. Therefore, in this study we plan to determine the maximum feasible dose (MFD) of Clofarabine in combination with 2Gy TBI that can achieve durable donor engraftment without causing excessive toxicity. The MFD determined from this pilot will be used in the next phase to study the outcomes after using this combination for SCT in this very high risk population.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Related Donor Arm Clofarabine Patients with related stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis. Related Donor Arm Total Body Irradiation Patients with related stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis. Related Donor Arm Stem Cell Transplantation Patients with related stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis. Unrelated Donor Arm Total Body Irradiation Patients with unrelated stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis. Unrelated Donor Arm Stem Cell Transplantation Patients with unrelated stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis. Related Donor Arm Cyclosporine Patients with related stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis. Related Donor Arm Mycophenolate Mofetil Patients with related stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis. Unrelated Donor Arm Clofarabine Patients with unrelated stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis. Unrelated Donor Arm Cyclosporine Patients with unrelated stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis. Unrelated Donor Arm Mycophenolate Mofetil Patients with unrelated stem cell donors. Patients will receive Clofarabine in combination with 2Gy total body irradiation (TBI) as a preparative regimen for stem cell transplantation, in turn followed by cyclosporine and Mycophenolate Mofetil as GVHD prophylaxis.
- Primary Outcome Measures
Name Time Method Maximum Feasible Dose of Clofarabine Day +100 The primary objective of the study is to determine the maximum feasible dose (MFD) of Clofarabine that can be given in combination with 2Gy total body irradiation as a non-myeloablative preparative regimen for allogeneic stem cell transplantation in pediatric patients with relapsed leukemia. The MFD is defined as the highest clofarabine dose associated with both an acceptably low toxicity and low non-engraftment (NE) rate. NE is defined as \< 5% donor T cells at any time point during serial monitoring. Monitoring during the evaluation period is required Day +30, +60 and +100.
- Secondary Outcome Measures
Name Time Method Days of Engraftment in Both Matched Related Donor (MRD) and Matched Unrelated Donor (MUD) Days +30, 60, 100, 180 Donor engraftment will be assessed by serial monitoring of T-cell (CD3) and myeloid (CD33) chimerism at day +30, 60, 100, 180 and 1 year at the local institution using PCR based VNTR/STR amplification techniques. Neutrophil engraftment is defined as first day of an ANC ≥500/μL on 3 consecutive measurements.
Transplant Related Mortality (TRM) at Day +100 Day 100 TRM is defined as any mortality within the first 100 days post stem cell infusion associated with regimen related toxicity, infection, or GVHD.
Days to Platelet Recovery Days +30, 60, 100, 180 Platelet recovery is defined as the first day of 3 consecutive measurements of platelets ≥20,000/μL after at least 7 days without transfusion support.
Trial Locations
- Locations (6)
Nationwide Childrens Hospital
🇺🇸Columbus, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Vanderbilt Children's Hospital
🇺🇸Nashville, Tennessee, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Childrens Hospital Los Angeles
🇺🇸Los Angeles, California, United States