Clinical trial NCT01158885
Conditions: Minimal Residual Disease Leukemia, Lymphoblastic, Acute Leukemia, Myelogenous, Acute
Keywords: relapsed relapse refractory Minimal Residual disease MRD MRD positive MRD+ ALL Acute lymphoblastic leukemia AML Acute myelogenous leukemia Relapsed AML
Sponsor: Therapeutic Advances in Childhood Leukemia Consortium
Start date: 2010-08-01; Completion date: 2012-10-24
Enrollment: 2 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study will test the ability of clofarabine + cytarabine to eliminate minimal residual disease (MRD) in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patients whose bone marrows exhibit complete remission by morphology. The toxicity profile of this regimen will be evaluated in addition to toxicity experienced by patients who proceed to stem cell transplant. Overall length of remission will also be collected.

Detailed description:
Recent studies have demonstrated that even low levels of minimum residual disease (MRD) (\>0.01% abnormal blasts) after aggressive re-induction therapy indicate a relatively poor outcome in relapsed acute lymphoblastic leukemia (ALL) patients, including those who proceed to allogeneic stem cell transplant (alloSCT). A similarly poor prognosis was seen in pediatric acute myelogenous leukemia patients with sub-morphologic disease prior to alloSCT. Studies to identify therapies that can eliminate persistent leukemia, have low toxicity profiles and can serve as a bridge to transplant are needed.

This study will test the ability of clofarabine + cytarabine to eliminate minimal residual disease (MRD) in acute myelogenous leukemia and acute lymphoblastic leukemia patients whose bone marrows exhibit complete remission by morphology. The toxicity profile of this regimen will be evaluated in addition to toxicity experienced by patients who proceed to stem cell transplant. Overall length of remission will also be collected.

Arms: arm 1: A maximum of two courses of the following regimen will be administered.

* Clofarabine: 20 mg/m2/day intravenously (IV) over 2 hours (given at hours 0 to 2) on days 1 through 5.
* Cytarabine intravenous: 1 gram/m2/day intravenously (IV) over 2 hours to be given 4 hours after the initiation of clofarabine on days 1 through 5.
* Methotrexate: to be given intrathecally (IT) to all acute lymphoblastic leukemia (ALL) patients on day 1 at the dose defined by age.
* Intrathecal (IT) cytarabine: is optional for acute myelogenous leukemia (AML) patients.
Interventions: intervention 1: Clofarabine intervention 2: Cytarabine intravenous intervention 3: Methotrexate intervention 4: Intrathecal (IT) Cytarabine
Intervention descriptions: intervention 1: 20 mg/m2/day intravenously (IV) over 2 hours (given at hours 0 to 2) on days 1 through 5. intervention 2: 1 gram/m2/day intravenously (IV) over 2 hours to be given 4 hours after the initiation of clofarabine on days 1 through 5. intervention 3: Methotrexate to be given intrathecally (IT) to all acute lymphoblastic leukemia (ALL) patients on day 1 at the dose defined by age below:

* 8 mg for patients age 1-1.99
* 10 mg for patients age 2-2.99
* 12 mg for patients 3-8.99 years of age
* 15 mg for patients \>9 years of age intervention 4: Intrathecal (IT) cytarabine is optional for acute myelogenous leukemia (AML) patients.

If intrathecal cytarabine is to be given, it must be given at least 72 hours but not more than 7 days prior to the initiation of intravenous cytarabine.

Dose should be given according to age as defined below:

* 30 mg for patients age 1-1.99
* 50 mg for patients age 2-2.99
* 70 mg for patients \>3 years of age

Protocol documents: