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

Inclusion Criteria

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.

• Age: Patients must be >1 and 750/ul.
• Donor Selection: Patient must have one of the appropriate donor types as described below:
• HLA identical sibling donor.
• 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).
• 1 allelic mis-matched unrelated donor (antigen mis-matches are not allowed).
• Stem Cell Source: The stem cell source from the donor must be one of the following:
• Bone Marrow or Peripheral blood stem cells (PBSC) from a matched related donor.
• PBSC from an unrelated donor. (Bone marrow is not acceptable for unrelated donors)
• Performance Level: Karnofsky > 50% for patients > 10 years of age and Lansky > 50% for patients 25%. If the SF is 30%. 3.3.9 Pulmonary Function Patient must have pulmonary function as defined below:
• DLCO >30%
• FVC/TLC >30%
• FEV1 > 30% of predicted
• 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.

• Patients with prior exposure to Clofarabine are eligible.
• 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.
• Protocol Approval: All institutional, FDA, and OHRP requirements for human studies must be met.

Exclusion Criteria

Patients will be excluded if they meet any of the following criteria:

• Infection
• Patients will be excluded if they have evidence of an active, progressive invasive infection. All patients with existing infections at the time study entry should be discussed with the study chair.
• Patients may have stable invasive infections and still be eligible.
• Patients with infections that are responsive to medical or surgical treatment as shown by radiographic and or microbial assessment may still be eligible.
• Patients will be excluded if they have an active, uncontrolled systemic fungal, bacterial, viral or other infection. All patients with existing infections at the time of study entry should be discussed with the study chair.
• An active uncontrolled infection is defined as exhibiting ongoing signs and symptoms related to the infection (fevers, positive blood cultures, chills, tachycardia, etc) despite appropriate antibiotics or other treatment.
• Patient has a diagnosis of CML or MDS.
• Patient has CNS 2 or CNS 3 status.
• Patient is HIV positive.
• Current or planned treatment with chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
• Use of investigational agents within 30 days or any anticancer therapy within 2 w