| Eligibility |
A. INCLUSION CRITERIA
1. Patients must be =1 and = 21 years of age when enrolled onto this study.
2. Diagnosis
- Patients must have a diagnosis of relapsed or refractory AML or ALL and,
- Patient must have an M1 marrow based upon a recovered marrow with less than 5%
blasts by conventional morphology and,
- 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 and
- Patients must be CNS 1.
3. Patient must have an 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
4. Performance Level Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for
patients =16 years of age.
5. Patient must have adequate venous access.
6. Prior Therapy
1. Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
2. At least 21 days must have elapsed from prior chemotherapy, at least 7 days must
have elapsed since receiving biological therapy.
3. It must be at least 45 days from any higher dose cytarabine therapy (>1 gm/
m2/day).
4. Patients on steroid taper must be on less than 0.5mg/kg/day with plans to
continue taper and discontinue the steroids.
7. Renal and Hepatic Function Patient must have adequate renal and hepatic functions as
indicated by the following laboratory values:
1. Patients must have a normal calculated creatinine clearance as calculated below:
- Pediatric Population (age <18): Calculated creatinine clearance = 90
ml/min/1.73m2 as calculated by the Schwartz formula for estimated glomerular
filtration rate (GFR) where GFR (ml/min/1.73 m2) = k*Height (cm)/serum
creatinine (mg/dl). k is a proportionality constant which varies with age
and is a function of urinary creatinine excretion per unit of body size;
0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70
adolescent boys.
- Adult Population (age =18): Serum creatinine =1.0 mg/dL; if serum creatinine
>1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be > 60
mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease
equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum
Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x
(1.212 if patient is black.
2. Conjugated (direct) serum bilirubin = 1.5 x ULN for age.
3. Alanine transaminase (ALT) = 2.5 × ULN for age.
4. Alkaline phosphatase = 2.5 × ULN for age.
5. Serum amylase = 1.5 ULN for age.
6. Serum Lipase is = ULN for age.
8. Patient must have a shortening fraction > 28% by echocardiogram or an ejection
fraction > 50% by MUGA
9. Reproductive Function
1. Female patients of childbearing potential must have a negative urine or serum
pregnancy test confirmed prior to enrollment.
2. Female patients with infants must agree not to breastfeed their infants while on
this study.
3. Male and female patients of child-bearing potential must agree to use an
effective method of contraception approved by the investigator during the study.
10. Patient must agree to submission of blood and bone marrow for MPF assessment of MRD to
TACL centralized lab.
B. EXCLUSION CRITERIA
Patients will be excluded if they meet any of the following criteria:
1. Patients with previous HSCT within previous 180 days.
2. Patients who have had prior treatment with clofarabine.
3. Patients with CNS2 or CNS 3 disease or bulky chloromatous disease.
4. Patients with Down Syndrome.
5. Patients with a previous history of veno-occlusive disease (VOD) or findings
consistent with a diagnosis of VOD, defined as: conjugated serum bilirubin >1.4 mg/dL
AND unexplained weight gain greater than 10% of baseline weight or ascites AND
hepatomegaly or right upper quadrant pain without another explanation, OR reversal of
portal vein flow on ultrasound, OR pathological confirmation of VOD on liver biopsy.
6. Patients with a systemic fungal, bacterial, viral, or other infection not controlled
(defined as exhibiting ongoing signs/symptoms related to the infection and without
improvement, despite appropriate antibiotics or other treatment).
7. Use of investigational agents within 30 days of planned treatment on this protocol.
8. Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy,
immunotherapy or other anti-cancer therapy other than is specified in the protocol.
9. Pregnant or lactating patients.
10. 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.
11. 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
intraepithelial 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.
12. Patient has active acute (greater than grade II) or active chronic extensive GVHD.
Patients who are on a tapering dose of immunosuppressants will be permitted (tapering
calcineurin inhibitor and/or less than 0.5 mg/kg/day of steroids).
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