Bridging Study to Eliminate Presence of MRD for Acute Leukemia Before HCT
Condition: Leukemia, Acute Lymphoblastic; Acute Myeloid Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
Intervention: Clofarabine; Cyclophosphamide; Etoposide
Intervention description: Days 1-5 receive Clofarabine 20 mg/m2 IV over 2 hours; Days 1-5 receive Cyclophosphamide 300 mg/m2 IV as a 30-60 minute infusion; Days 1-5 receive Etoposide 100 mg/m2 IV over 2 hours
Intervention MeSH terms: Cyclophosphamide; Etoposide; Clofarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Maximum age: 39 Years
Healthy volunteers: No

Summary:

      This is a Phase 2 study designed for the purpose of estimating various parameters surrounding
      the efficacy of Clofarabine, Cyclophosphamide and Etoposide in eliminating minimal residual
      disease (MRD) in acute leukemia patients otherwise in remission and without causing
      significant delay of HCT due to treatment related toxicity.

      A single course of "bridge" chemotherapy is given prior to the transplant procedure as an
      approach to improved disease-free survival in a patient group who historically has had
      inferior outcomes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) with <
             5% blasts in the bone marrow (M1) by morphology and that meets one of the following
             criteria:

        Flow cytometric evidence of MRD (≥ 0.01% leukemic blasts for ALL or ≥ 0.5% leukemic blasts
        for AML detected in the bone marrow) OR Molecular/cytogenetic evidence of disease (FISH or
        PCR methodology) performed within 7 days And with the intent of going on to an allogeneic
        hematopoietic cell transplantation (HCT) independent of this study

          -  Patients must have an available donor and have intention of proceeding directly to
             ALL-HCT after completion of 1 cycle of Bridging therapy.

          -  Age 0 to 39 years

          -  Karnofsky Performance Status ≥ 50% for patients 16 years and older and Lansky Play
             Score ≥ 50 for patients under 16 years of age (see Appendix 2)

          -  Patients must have a life expectancy ≥ 8 weeks as determined by the enrolling
             investigator

          -  Have acceptable organ function as defined within 7 days of study registration

        Renal: creatinine clearance ≥ 60 mL/min/1.73 m2 or serum creatinine based on age/gender as
        follows:

        Hepatic: ALT < 5 x upper limit of normal (ULN) and total bilirubin ≤ 1.5 x upper limit of
        normal (ULN) for age Cardiac: left ventricular ejection fraction ≥ 40% by ECHO/MUGA

          -  Patients must have fully recovered from the acute toxic effects of all prior
             chemotherapy, immunotherapy, or radiotherapy prior to entering this study. At least 7
             days must have elapsed from prior chemotherapy.

          -  Hematopoietic Growth Factors: At least 7 days since the completion of therapy with a
             growth factor and at least 14 days since pegfilgrastim (Neulasta®) administration.

          -  Sexually active females of child bearing potential must agree to use adequate
             contraception (diaphragm, birth control pills, injections, intrauterine device [IUD],
             surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration
             of treatment and for 2 months after the last dose of chemotherapy. Sexually active men
             must agree to use barrier contraceptive for the duration of treatment and for 2 months
             after the last dose of chemotherapy.

          -  Voluntary written consent before performance of any study-related procedure not part
             of normal medical care, with the understanding that consent may be withdrawn by the
             subject at any time without prejudice to future medical care.

        Exclusion Criteria:

          -  Acute Promyelocytic Leukemia (APL)

          -  Active extramedullary disease (CNS ≥ CNS2 and/or testicular leukemia) or presence of
             chloromatous disease

          -  Receiving concomitant chemotherapy, radiation therapy; immunotherapy or other
             anti-cancer therapy other than is specified in the protocol

          -  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)

          -  Pregnant or lactating. The agents used in this study are known to be teratogenic to a
             fetus and there is no information on the excretion of agents into breast milk. All
             females of childbearing potential must have a blood test or urine study within 2 weeks
             prior to registration to rule out pregnancy.

          -  Known allergy to any of the agents or their ingredients used in this study

          -  Participating in a concomitant Phase 1 or 2 study