Clofarabine With Cytarabine for Patients With Minimal Residual Disease Positive Leukemia

Inclusion Criteria: Patients must meet all of the following criteria to be eligible to participate in the study.

Patients must be ≥1 and ≤ 21 years of age when enrolled onto this study.

• Diagnosis (Patient must have all of the following)

  • Patients must have a diagnosis of relapsed acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL)
  • Patient must have an M1 marrow based upon a recovered marrow with less than 5% blasts by conventional morphology
  • Patient must have minimal residual disease (MRD) detected by either multidimensional or conventional flow cytometry greater than 0.1% and less than 5% following any re-induction attempt
  • Patients must have a central nervous system (CNS) disease status of 1
• Patient must have an absolute neutrophil count (ANC) >500/μL off cytokine support for at least 24 hours and platelets >50,000 K/μL without platelet transfusion in the past seven days
• Karnofsky > 50% for patients > 10 years of age and Lansky > 50% for patients ≤ 10 years of age.
• Patient must have adequate venous access.
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• At least 21 days must have elapsed from prior chemotherapy, at least 7 days must have elapsed since receiving biological therapy.
• It must be at least 90 days from any higher dose cytarabine therapy (>1 gm/ m2/day).
• Patients must have a normal calculated creatinine clearance

• Patient must have

  1. Conjugated (direct) serum bilirubin ≤ 1.5 x upper limit of normal (ULN) for age.
  2. Alanine transaminase (ALT) ≤ 2.5 × ULN for age.
  3. Alkaline phosphatase ≤ 2.5 × ULN for age.
  4. Serum amylase ≤ 1.5 ULN for age.
  5. Serum Lipase is ≤ ULN for age.
• Patient must have a shortening fraction > 28% or an ejection fraction > 50%.
• Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
• Female patients with infants must agree not to breastfeed their infants while on this study.
• Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study.
• Patient must agree to submission of blood and bone marrow for assessment of minimal residual disease (MRD).
• All patients and/or their parents or legal guardians must sign a written informed consent.

Exclusion Criteria:Patients who meet any of the following criteria will be excluded from participating in the study.

• Patients with previous hematopoietic stem cell transplant (HSCT) within previous six months.
• Patients who have had prior treatment with clofarabine.
• Patients with CNS2 or CNS 3 disease or bulky chloromatous disease.
• Patients with Down Syndrome.
• Patients with a previous history of veno-occlusive disease (VOD) or findings consistent with a diagnosis of VOD.
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled.
• Use of investigational agents within 30 days of planned treatment on this protocol.
• Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy, immunotherapy or other anti-cancer therapy other than is specified in the protocol.
• Pregnant or lactating patients.
• Any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.

• Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy with the following exceptions:

  1. Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intra-epithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed.
  2. Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed.