Sorafenib in Treating Young Patients With Relapsed or Refractory Solid Tumors or Leukemia

Inclusion Criteria:

• Diagnosis of 1 of the following:

  • Histologically confirmed malignant solid tumor at original diagnosis or relapse

    • Measurable or evaluable disease by CT scan or MRI

  • Histologically confirmed leukemia, including 1 of the following:

    • Acute lymphoblastic leukemia (ALL)

      • Greater than 25% blasts in the bone marrow (M3 bone marrow)

    • Acute myeloid leukemia (AML)

      • Greater than 25% blasts in the bone marrow (M3 bone marrow)

    • AML and FLT3-ITD mutation

      • Patients must have ? 5% blasts in the bone marrow
      • Active extramedullary disease (except leptomeningeal disease) allowed

    • Juvenile myelomonocytic leukemia (JMML) meeting the following criteria:

      • Peripheral blood monocytosis > 1,000/mm^3
      • Blasts (including promonocytes) are < 20% of the WBCs in the blood and of the nucleated bone marrow cells
      • No Philadelphia chromosome (Ph) or BCR/ABL fusion gene

      • Has ? 2 of the following additional diagnostic criteria:

        • Hemoglobin F increased for age
        • Immature granulocytes in the peripheral blood
        • WBC > 10,000/mm^3
        • Clonal chromosomal abnormality (e.g., may be monosomy 7)
        • Sargramostim (GM-CSF) hypersensitivity of myeloid progenitors in vitro

    • Chronic myelogenous leukemia (CML) in blast crisis

      • Greater than 25% blasts in the bone marrow (M3 bone marrow)
      • Patients with Ph-positive CML must be refractory to imatinib mesylate

• Relapsed or refractory disease

  • Patients with acute promyelocytic leukemia (APL) must be refractory to treatment with tretinoin and arsenic trioxide
• Standard curative therapies or therapies proven to prolong survival with an acceptable quality of life do not exist
• Active extramedullary disease, except active leptomeningeal leukemia, allowed
• No brain tumors or known brain metastases
• Karnofsky performance status (PS) 50-100% (for patients > 10 years of age)
• Lansky PS 50-100% (for patients ? 10 years of age)

• Patients with solid tumors must have adequate bone marrow function, as defined by the following:

  • Absolute neutrophil count ? 1,000/mm^3
  • Platelet count ? 75,000/mm^3 (transfusion independent)
  • Hemoglobin ? 8.0 g/dL (red blood cell [RBC] transfusions allowed)

• Patients with leukemia may have abnormal blood counts but must meet the following criteria:

  • Platelet count ? 20,000/mm^3 (platelet transfusions allowed)
  • Hemoglobin ? 8.0 g/L (RBC transfusions allowed)

• Patients with acute myeloid leukemia and FLT3-ITD mutation

  • Platelet count ? 20,000/mm^3
• Lipase and amylase normal

• Creatinine clearance or radioisotope glomerular filtration rate ? 70 mL/min OR creatinine normal based on age as follows:

  • No greater than 0.8 mg/dL (for patients 5 years of age and under)
  • No greater than 1.0 mg/dL (for patients 6-10 years of age)
  • No greater than 1.2 mg/dL (for patients 11-15 years of age)
  • No greater than 1.5 mg/dL (for patients over 15 years of age)

• Patients with solid tumors must meet the following criteria:

  • Bilirubin normal for age
  • ALT normal for age (for the purpose of this study, the upper limit of normal [ULN] for ALT is 45 ?/L)
  • Serum albumin ? 2 g/dL

• Patients with leukemia must meet the following criteria:

  • Bilirubin (sum of conjugated + unconjugated) ? 1.5 times ULN for age
  • ALT ? 5.0 times ULN for age (? 225 ?/L) (for the purpose of this study, the ULN for ALT is 45 ?/L)
  • Serum albumin ? 2 g/dL
• Albumin ? 2 g/dL
• PT, PTT, and INR normal (for patients on prophylactic anticoagulation)
• No evidence of dyspnea at rest
• No exercise intolerance
• Pulse oximetry >94% on room air, if there is clinical indication for determination
• Diastolic blood pressure ? the 95th percentile for age and gender (height included for AML and FLT3-ITD mutation patients)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• Able to swallow tablets
• No evidence of bleeding diathesis
• No other medical condition or situation that would preclude study compliance
• No known Gilbert syndrome
• Fully recovered from prior chemotherapy, immunotherapy, or radiotherapy (for patients with solid tumors)
• Recovered from the non-hematologic toxic effects of all prior therapy (for patients with leukemia)
• Recovered from acute non-hematologic toxic effects of all prior anti-cancer chemotherapy (for patients with AML and FLT3-ITD mutation)
• At least 7 days since prior hematopoietic growth factors
• At least 7 days since prior biologic agents
• At least 2 weeks since prior local palliative radiotherapy (small port)
• At least 3 months since prior total-body irradiation, craniospinal radiotherapy, or radiation to ? 50% of the pelvis
• At least 6 weeks since other prior substantial bone marrow radiation (e.g., skull, spine, pelvis, ribs)

• At least 3 months since prior stem cell transplantation or rescue (for patients with solid tumors)

  • No evidence of active graft-vs-host disease
• At least 3 months since prior myeloablative therapy followed by bone marrow or stem cell transplantation (for patients with leukemia)

• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) (for patients with solid tumors)

  • At least 24 hours since prior nitrosoureas (for patients with AML and FLT3-ITD mutation)
• At least 2 weeks since prior chemotherapy (for patients with leukemia)
• At least 3 weeks since prior monoclonal antibody therapy
• No prior sorafenib
• No other concurrent investigational drugs

• No other concurrent anticancer agents or therapies, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy

  • Concurrent maintenance-like chemotherapy for patients with AML and FLT3-ITD mutation allowed

• No concurrent administration of any of the following:

  • Cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
  • Rifampin
  • Grapefruit juice
  • Hypericum perforatum (St. John wort)

• No concurrent therapeutic anticoagulation

  • Concurrent prophylactic anticoagulation (e.g., low-dose warfarin) of venous or arterial access devices allowed provided the requirements for PT, INR, or PTT are met