Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia
Condition: Childhood Acute Promyelocytic Leukemia (M3); Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Juvenile Myelomonocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Burkitt Lymphoma; Lymphoma; Neoplasms; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neuroblastoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Medulloblastoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Leukemia, Promyelocytic, Acute; Lymphomatoid Granulomatosis; Rhabdoid Tumor; Leukemia, Myelomonocytic, Juvenile; Recurrence
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I trial is studying the side effects and best dose of vorinostat when given
      together with isotretinoin in treating young patients with recurrent or refractory solid
      tumors, lymphoma, or leukemia. Drugs used in chemotherapy, such as vorinostat, work in
      different ways to stop the growth of cancer cells, either by killing the cells or by stopping
      them from dividing. Vorinostat may also stop the growth of cancer cells by blocking some of
      the enzymes needed for cell growth and by blocking blood flow to the cancer. Isotretinoin may
      cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving
      vorinostat together with isotretinoin may be an effective treatment for cancer.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. Determine the maximum tolerated dose (MTD) of vorinostat (SAHA) in young patients with
      recurrent or refractory solid tumors or lymphomas.

      II. Determine the MTD of SAHA administered in combination with isotretinoin in young patients
      with recurrent or refractory neuroblastoma, medulloblastoma/CNS primitive neuroectodermal
      tumor, or atypical teratoid rhabdoid tumor.

      III. Determine the tolerability of the solid tumor MTD of SAHA in young patients with
      recurrent or refractory leukemia.

      IV. Determine the toxic effects of SAHA administered with or without isotretinoin in these
      patients.

      V. Determine the pharmacokinetics of this drug in these patients.

      SECONDARY OBJECTIVES:

      I. Determine, preliminarily, the antitumor activity of SAHA administered with or without
      isotretinoin in these patients.

      II. Correlate the pharmacokinetics of this drug with genetic polymorphisms (e.g., UGT1A1) in
      these patients.

      OUTLINE: This is a multicenter, dose-escalation study of vorinostat (SAHA).

      Group 1 (solid tumor or lymphoma patients): Patients receive oral SAHA once daily on days
      1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease
      progression or unacceptable toxicity.Cohorts of 3-6 patients receive escalating doses of SAHA
      until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
      preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An
      additional 6 patients may be treated at the MTD.

      Group 2 (leukemia patients): Patients receive SAHA as in group 1 at the MTD.

      Group 3 (select solid tumor patients): Patients receive oral isotretinoin twice daily on days
      1-14. Patients also receive SAHA once daily on days 1-28 OR once on days 1, 3, 5, 8, 10, 12,
      15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 courses in the
      absence of disease progression or unacceptable toxicity.The MTD of SAHA is determined as in
      group 1. An additional 6 patients may be treated at the MTD.

      After completion of study treatment, patients are followed periodically.
    

Intervention name(s): vorinostat; isotretinoin
Intervention type(s): Drug; Drug
Intervention description(s): Given orally; Given orally
Other intervention name(s): L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza; 13-CRA; Amnesteem; Cistane; Claravis; Sotret
Intervention MeSH terms: Vorinostat; Isotretinoin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment