Clofarabine and Low Dose Total Body Irradiation as a Preparative Regimen for Stem Cell Transplant in Leukemia.

Since this is a Phase 1 study, any patient who is a candidate for a non-myeloablative SCT because he/she cannot tolerate the standard myeloablative preparative therapy is eligible for this trial. Briefly, the following groups of patients will be targeted and are eligible for this trial:

Patients with presence of organ system dysfunction or severe systemic infections that significantly increase the risk of TRM with standard myeloablative regimens.

History of previous myeloablative allogeneic or autologous transplantation.

Heavily pre-treated leukemia patients, eg. Patients in CR after failure of ≥2 prior regimens.(eg. ALL CR ≥ 3).

Combination of toxicities or co-morbidities that leads the investigator to feel that the child is at high risk (\>50%) of TRM with standard ablative regimens.

The eligibility criteria listed below are interpreted literally and cannot be waived.

1. Age: Patients must be \>1 and \< 21 years of age at the of study entry.

2. Diagnosis

1. Patients must have a diagnosis of ALL or AML.

* ALL patients must be in clinical remission defined as BM morphology \<5% blasts and CNS 1 status.

* AML patients must be in M1 (\<5% blasts) or M2 (\<20% blasts) marrow status with CNS 1 status.

2. Patient must have an ANC \> 750/ul.

3. Donor Selection: Patient must have one of the appropriate donor types as described below:

1. HLA identical sibling donor.

2. Complete matched unrelated donor, (matched at A, B, C, DR B1 and DQ, B1 at the allelic level based on high resolution typing for Class I and II antigens, 10/10 match).

3. 1 allelic mis-matched unrelated donor (antigen mis-matches are not allowed).

4. Stem Cell Source: The stem cell source from the donor must be one of the following:

1. Bone Marrow or Peripheral blood stem cells (PBSC) from a matched related donor.

2. PBSC from an unrelated donor. (Bone marrow is not acceptable for unrelated donors)

5. Performance Level: Karnofsky \> 50% for patients \> 10 years of age and Lansky \> 50% for patients \< 10 years of age.

6. Reproductive Function

1. Female patients of childbearing potential must have a negative serum pregnancy test confirmed within 2 weeks 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.

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 calculated creatinine clearance ≥ 70mL/min/m2 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.

2. Total serum bilirubin \< 2 mg/dL.

3. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 5 × ULN.

8. Cardiac Function: Patient must have a shortening fraction (SF) \> 25%. If the SF is \<25%, patient must have an ejection fraction (EF) by MUGA of \>30%. 3.3.9 Pulmonary Function Patient must have pulmonary function as defined below:

1. DLCO \>30%

2. FVC/TLC \>30%

3. FEV1 \> 30% of predicted

4. Patient is not on continuous oxygen

If patient is not old enough or unable to comply with pulmonary function tests, they must have a pulse ox \>92% in room air and not be on continuous oxygen.

9. Patients with prior exposure to Clofarabine are eligible.

10. Informed Consent: Patients and/or their parents or legal guardians must be capable of understanding the investigational nature, potential risks and benefits of the study. All patients and/or their parents or legal guardians must sign a written informed consent. Age appropriate assent will be obtained per institutional guidelines. To allow non-English speaking patients to participate in this study, bilingual health services will be provided in the appropriate language when feasible.

11. Protocol Approval: All institutional, FDA, and OHRP requirements for human studies must be met.

What this study is about