Clinical trial NCT01041508
Conditions: Leukemia Lymphoblastic, Acute Acute Myeloid Leukemia Neoplasm Recurrent
Keywords: ALL AML Recurrence Relapsed Stem Cell Transplant Non-myeloablative
Sponsor: Therapeutic Advances in Childhood Leukemia Consortium
Start date: 2010-01-29; Completion date: 2014-08-01
Enrollment: 18 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: Clofarabine intervention 2: Total Body Irradiation intervention 3: Stem Cell Transplantation intervention 4: Cyclosporine intervention 5: Mycophenolate Mofetil
Intervention descriptions: intervention 1: Clofarabine will be given as an intravenous infusion over 2 hours on days -6 though -2. The dose of Clofarabine will be assigned at study entry (30, 40 or 52 mg/m2). intervention 2: Low dose (2 Gy) TBI will be administered from a linear accelerator at ≤ 20 cGy/min on day "0" according to institutional guidelines. intervention 3: Patients will be infused with 'unmanipulated' hematopoietic stem cells from a related or unrelated donor on day 0 of the treatment regimen according to institutional practice guidelines. intervention 4: Cyclosporine is given IV based on body weight at:

* Age ≤ 6 years old: 6 mg/kg IV QD. in divided doses (e.g. 2 mg/kg q8hrs).
* Age \> 6 years old: 3 mg/kg IV QD in divided doses (1.5mg/kg q12hrs)

Cyclosporine should be started on day -1 after completion of Clofarabine. Levels should be maintained between 300-400 ng/ml. intervention 5: MMF will be at 15 mg/kg, based on adjusted body weight, q 8 hours (45 mg/kg/day; max.3g/day) PO, or IV if indicated, from the evening of day 0 (i.e. first dose 4-6 hours following stem cell infusion) to day +40 post-transplant. Oral doses will be rounded to the nearest 250 mg (capsules are 250 mg). MMF is also available in oral suspension form. MMF will be given until day +40 post transplant and then tapered by 10% per week to be discontinued by day +90.

Protocol documents: