Safety Study of CPX-351 in Children With Relapsed Leukemia or Lymphoma

• Age

  1. 12 months to 21 years at time of enrollment into dose exploration phase
  2. 12 months to 30 years at time of enrollment into expanded phase
• Diagnosis: Patients must have a diagnosis of a hematologic malignancy (acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or aggressive lymphoma.

• Disease Status

  1. Acute myeloid leukemia - patients with non-therapy related AML must be in first or greater relapse or have refractory disease to at least two courses of induction therapy.
  2. Acute lymphoid leukemia - patients with ALL must be in second or greater relapse or have relapsed disease refractory to re-induction therapy.
  3. Aggressive Lymphoma - patients must have relapsed or refractory disease for which there is no known curative therapy available. Patients must have measurable disease by CT scan.
• Performance status: Karnofsky > or = to 50% or Lansky > or = to 50.

• Prior therapy: Patients must have fully recovered from acute toxicities of prior therapy.

  1. Hematopoetic Stem cell transplant (HSCT): Patients who relapsed after HSCT, are eligible provided they have no evidence of active graft versus host disease (GVHD) and are at least 2 months post-transplant.
  2. Anthracycline exposure: Patients who have not previously had TBI (total body irradiation) must have a total previous cumulative anthracycline exposure ≤ 450 mg/m2 daunorubicin equivalents. Patients who have had prior TBI or radiation to the mediastinum must have a previous cumulative anthracycline exposure e ≤ 300 mg/m2 daunorubicin equivalents.

  3. Cytotoxic therapy:

     1. AML and Lymphoma: at least 14 days must have elapsed since the completion of systemic cytotoxic therapy, with the exception of hydroxyurea.
     2. ALL: patients who relapsed while receiving standard maintenance therapy do not have a waiting period. At least 14 days must have elapsed since receiving systemic cytarabine or an anthracycline/anthracenedione.
     3. Intrathecal cytotoxic therapy: no waiting period is required for patients receiving intrathecal cytarabine, methotrexate and/or hydrocortisone. At least 14 days must have elapsed since receiving liposomal cytarabine in intrathecal injection.

• Organ function requirements

  1. Adequate bone marrow function - platelet count >/= 20,000/uL (may receive platelet transfusions; Hemoglobin >/= 8 g/dL (may receive red blood cell transfusions)
  2. Adequate Renal function - a maximum serum creatinine is based on age/gender. Subjects that do not meet eligibility criteria based upon serum creatinine may meet eligibility criteria based upon a 24 hour creatinine clearance or radioisotope determined GFR >/= 70 mL/min/1.73 m2.
  3. Adequate liver function - Direct bilirubin \</= 1.5 x upper limit of normal (ULN) for age and SGPT (ALT) \< 5.0 x upper limit of normal (ULN) for age and institution (unless elevation is related to leukemia involvement).
  4. Adequate cardiac function - Shortening fraction of >/= 27% by echocardiogram, or Ejection fraction of >/= 50% by gated radionuclide study or echocardiogram.
  5. Central Nervous system function - patients with seizure disorder may be enrolled if on anticonvulsants and well controlled and CNS toxicity \</= Grade 2.

Exclusion Criteria:

• Patients with the following diagnosis are not eligible: acute promyelocytic leukemia (APML), Down Syndrome, Fanconi Anemia, acute lymphoblastic leukemia with central nervous system leukemia (CNS status 3), Wilson's disease
• Pregnant or breast-feeding women. Males and females of reproductive potential may not participate unless they have agreed to use an effective method of contraception.

• Concomitant medications

  1. Growth factors- growth factors that support platelet or white cell number or function must not be administered within 7 days prior to enrollment.
  2. Investigational drugs - patients currently receiving another investigational drug are not eligible.
  3. Anti-cancer agents- patients who are currently receiving other anti-cancer agents are not eligible with the exception of intrathecal cytarabine and oral hydroxyurea. Hydroxyurea must be discontinued 24 hours prior to initiation of protocol therapy.
• Infection: Patients who have an uncontrolled infection are not eligible.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
• History of Wilson's disease or other copper-metabolism disorder
• Major surgery within 4 weeks of enrollment.
• Greater than 13.6 Gy prior radiation to the mediastinum