Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia
Childhood Acute Promyelocytic Leukemia (M3), Childhood Atypical Teratoid/Rhabdoid Tumor, Childhood Burkitt Lymphoma
About this trial
This is an interventional treatment trial for Childhood Acute Promyelocytic Leukemia (M3)
Eligibility Criteria
Inclusion Criteria: Histologically confirmed* diagnosis of 1 of the following: Recurrent or refractory solid tumor or lymphoma (for patients in group 1) Measurable or evaluable disease Recurrent or refractory leukemia (for patients in group 2) Greater than 25% blasts in the bone marrow (i.e., M3 bone marrow) Active extramedullary disease allowed except leptomeningeal disease Recurrent or refractory CNS tumor of 1 of the following types (for patients in group 3): Neuroblastoma Medulloblastoma/CNS primitive neuroectodermal tumor Atypical teratoid rhabdoid tumor No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists No bone marrow involvement by disease (for patients in groups 1 and 3) No active CNS leukemia Performance status - Lansky 50-100% (for patients ≤ 10 years of age) Performance status - Karnofsky 60-100% (for patients > 10 years of age) Absolute neutrophil count ≥ 1,000/mm^3 (for solid tumor patients) Platelet count ≥ 100,000/mm^3* (for solid tumor patients) (20,000/mm^3** for leukemia patients) Hemoglobin ≥ 8.0 g/dL (RBC transfusion allowed) (for solid tumor and leukemia patients) Triglycerides < 300 mg/dL (for patients in group 3) Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT ≤ 5 times ULN Albumin ≥ 2 g/dL Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min Creatinine based on age as follows: No greater than 0.8 mg/dL (for patients ≤ 5 years of age) No greater than 1.0 mg/dL (for patients 6 to 10 years of age) No greater than 1.2 mg/dL (for patients 11 to 15 years of age) No greater than 1.5 mg/dL (for patients over 15 years of age) Negative dipstick for protein OR < 1,000 mg protein/24 hour urine collection (for patients in group 3) No evidence of gross hematuria (for patients in group 3) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Body surface area ≥ 0.5 m^2 Neurologic deficits in patients with CNS tumors must be stable for ≥ 1 week before study entry Able to swallow whole capsules No uncontrolled infection Skin toxicity < grade 1 (for patients in group 3) Recovered from prior immunotherapy At least 7 days since prior hematopoietic growth factors At least 7 days since prior antineoplastic biologic agents At least 2 months since prior stem cell transplantation or rescue No evidence of active graft-versus-host disease No other concurrent biologic therapy or immunotherapy More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered No concurrent chemotherapy Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for ≥ 7 days prior to study entry No concurrent dexamethasone for antinausea or antiemetic therapy Recovered from prior radiotherapy At least 2 weeks since prior local, palliative, small-port radiotherapy At least 3 months since prior total-body irradiation, radiotherapy to the craniospinal area, or radiotherapy to ≥ 50% of the pelvis At least 6 weeks since other prior substantial radiotherapy to the bone marrow No concurrent radiotherapy At least 2 weeks since prior valproic acid No other concurrent investigational agents No other concurrent anticancer therapy No concurrent enzyme-inducing anticonvulsants
Sites / Locations
- Children's Oncology Group
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Arm I
Arm II
Arm III
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.