T2011-002 A Phase I Study of 5-Azacytidine in Combination with Chemotherapy for Children with Relapsed or Refractory ALL or AML
This research is being done to find out if AZA can be safely given before treatment with standard chemotherapy drugs in people who have acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) that has relapsed. Relapse means the leukemia has come back after treatment. 5- Azacytidine (AZA) is a drug approved by the FDA (Food and Drug Administration) for the treatment ofmyelodysplastic syndrome, which is a cancer very similar to leukemia. This drug is thought to work by turning on genes that limit the growth of cancer cells. AZA have been given to children and adults with AML or ALL, and has been given together with other chemotherapy.The goals of this study are:-To evaluate the side effects (good and/or bad) of giving AZA before chemotherapy using the standard drugs fludarabine and cytarabine.-To see if receiving AZA with chemotherapy changes the DNA in the cancer cells found in blood and bone marrow.-To measure how effective the combination of AZA with standard chemotherapy drugs is at treating children and young adults with relapsed AML.
Patients must be ï¿½ 1 and ï¿½21 years of age. Patients with AML must have ï¿½5% blasts (by morphology) in the bone marrow. Patients with ALL must have an M2 or M3 marrow (ï¿½5% blasts by morphology). Patients may have CNS or other sites of extramedullary disease. No cranial irradiation is allowed during the protocol therapy. Patients with secondary AML are eligible. Patients with Down syndrome and DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. Disease requirements: Any patient with AML in 1st or greater relapse, OR Any patient with ALL in 2nd or greater relapse, OR Patients with AML or ALL failed to go into remission after first or greater relapse, OR Patients with AML or ALLfailed to go into remission from original diagnosis after two or more courses of induction attempts. Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD) and are at least 90 days post-transplant at the time of enrollment. Patients must have adequate renal and hepatic functions.
During the study: Subjects will be enrolled in groups of 6 to one of the series of AZA dose levels shown below. The starting dose level is dose level 1. If the side effects at that dose level are not too severe, this dose levelwill be used to complete the study. However, if the side effects at dose level 1 are too severe, the dose will be decreased to the level 0 dose. You will receive AZA for 5 days during this trial. AZA will be given by injection under the skin on days 1-5. This schedule is believed to allow for the greatest effect of AZA on the leukemia cells. The other standard chemotherapy will start on day 6. Fludarabine and cytarabine are given through your vein fromdays 6-10 for total 5 days in a row. It will generally take you 5-6 weeks for your bone marrow to recover. This 5-6 week period is called a course. You will receive 2 courses of chemotherapy unless the regimen is not working or you have unacceptable side effects from the regimen. Please keep in mind that in an adult study, many people who didnï¿½t respond to the first course of study regimen responded to the second course of study regimen. Therefore,2 courses of chemotherapy are strongly recommended. The regimen for the 2 courses of study drugs will last about 2-3 months. At the end of each course, you will have an evaluation to see how your leukemia is responding to the study drugs.
07/31/2014 04:02 AM