MLN8237 in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

  • Histologically confirmed malignant solid tumor at original diagnosis or relapse

    • Neuroblastoma
    • Rhabdomyosarcoma (RMS)
    • Osteosarcoma
    • Ewing sarcoma/peripheral primitive neuroectodermal tumor
    • Non-RMS soft tissue sarcoma
    • Hepatoblastoma
    • Malignant germ cell tumor
    • Wilms tumor

    • Rhabdoid tumor

      • Morphology and immunophenotypic panel consistent with rhabdoid tumor (required)
      • Loss of INI1 confirmed by immunohistochemistry
      • Molecular confirmation of tumor-specific bi-allelic INI1 loss/mutation if INI1 immunohistochemistry is not available

  • Histologically confirmed leukemia recurrent or refractory to ≥ 2 prior induction or treatment regimens (must not be known to be refractory to red blood cell or platelet transfusions)

    • Acute lymphoblastic leukemia

      • > 25% blasts in the bone marrow (M3 bone marrow), excluding known CNS disease

    • Acute myeloid leukemia

      • ≥ 5 % blasts in the bone marrow (M2/M3 bone marrow), excluding known CNS disease

• Radiographically measurable disease for solid tumors

  • Patients with neuroblastoma who do not have measurable disease but have iodine-123 metaiodobenzylguanidine (¹²³ I-MIBG)-positive lesions allowed

  • None of the following qualify as measurable disease:

    • Malignant fluid collections (e.g., ascites, pleural effusions)
    • Bone marrow infiltration
    • Lesions detected by nuclear medicine studies (e.g., bone, gallium, or PET scans)
    • Elevated tumor markers in plasma or cerebrospinal fluid
    • Previously irradiated lesions that have not demonstrated clear progression after radiotherapy
• No CNS disease (leukemia patients)

PATIENT CHARACTERISTICS:

• ECOG performance score (PS) 0-2

  • Karnofsky PS 50-100% (for patients > 16 years of age)
  • Lansky PS 50-100% (for patients ≤ 16 years of age)

• ANC ≥ 1,000/mm³

  • ANC ≥ 750/mm³ (solid tumor and known bone marrow metastatic disease)
  • Transfusion allowed
• Hemoglobin ≥ 8.0 g/dL (RBC transfusion allowed)

• Platelet count ≥ 100,000/mm³ (transfusion independent, > 7 days since platelet transfusion )

  • Platelet count ≥ 50,000/mm³ (solid tumor and known bone marrow metastatic disease)

  • Transfusion allowed

    • Not refractory to RBC or platelet transfusions

• Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR a serum creatinine based on age and/or gender as follows:

  • 0.6 mg/dL (1 to < 2 years of age)
  • 0.8 mg/dL (2 to < 6 years of age)
  • 1.0 mg/dL (6 to < 10 years of age)
  • 1.2 mg/dL (10 to < 13 years of age)
  • 1.5 mg/dL (male) and 1.4 mg/dL (female) (13 to < 16 years of age)
  • 1.7 mg/dL (male) and 1.4 mg/dL (female) (≥ 16 years of age)
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT ≤ 5.0 times ULN
• Serum albumin ≥ 2 g/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study therapy
• Not unable to swallow capsules
• No uncontrolled infection
• No patient who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Fully recovered from all prior chemotherapy, immunotherapy, or radiotherapy
• More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea) (solid tumor patients)

• At least 14 days since prior cytotoxic therapy (leukemia patients)

  • Patients who relapse during standard maintenance therapy are not required to wait 14 days
  • At least 24 hours since prior cytoreduction with hydroxyurea
• More than 7 days since prior growth factors (14 days for pegfilgrastim [Neulasta])
• At least 7 days since prior biologic agent (antineoplastic agent)
• At least 3 half-lives since prior monoclonal antibody therapy

• At least 2 weeks since prior local palliative radiotherapy (small port)

  • At least 6 weeks since prior therapeutic doses of ¹²³ I-MIBG or other substantial bone marrow irradiation
  • At least 6 months since prior craniospinal radiotherapy, radiotherapy to ≥ 50% of the pelvis, or total-body irradiation
• At least 3 months since stem cell transplantation with no evidence of active graft-vs-host disease
• Concurrent corticosteroids allowed provided patient is on a stable or decreasing dose for ≥ 7 days before study enrollment
• No other concurrent investigational drugs
• No other concurrent anticancer agents, including chemotherapy, radiotherapy, or immunomodulating agents
• No concurrent daily benzodiazepine therapy
• No concurrent P-glycoprotein substrates (e.g., digoxin, cyclosporine, tacrolimus, or sirolimus)