ELIGIBILITY CRITERIA:
INCLUSION CRITERIA FOR PATIENTS WITH SOLID TUMORS:
AGE: Patients must be greater than or equal to 2 years and less than or equal to 18 years of age.
DIAGNOSIS: Histologically confirmed solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms' tumor, hepatic tumors, germ cell tumors, and primary brain tumors. In patients with brain stem or optic gliomas the requirement for histological confirmation may be waived.
MEASURABLE/EVALUABLE DISEASE: Patients must have measurable or evaluable tumors.
PRIOR THERAPY:
- The patient's cancer must have relapsed after or failed to respond to frontline curative therapy and there must not be other potentially curative treatment options available. Curative therapy may include surgery, radiation therapy, chemotherapy, or any combination of these modalities.
- Patients must have had their last dose of radiation therapy at least four weeks prior to study entry, their last dose of chemotherapy at least 28 days prior to study entry (6 weeks for nitrosoureas), and their last dose of any investigational cancer therapy at least 30 days prior to study entry.
- Patients must have recovered from the toxic effects of all prior therapy before entry onto this trial.
- Patients with brain tumors must be on a stable or tapering dose of corticosteroids for 7 days prior to the baseline scan performed for the purpose of assessing response to therapy on this study.
- Patients should be off colony stimulating factors such as Filgrastim (G-CSF), sargramostim (GM-CSF), and IL-11 (with the exception of erythropoietin) for at least 72 hours prior to study entry.
PERFORMANCE STATUS: Patients greater than 10 years must have a Karnofsky performance level greater than or equal to 50, and children less than or equal to 10 years must have a Lansky performance level greater than or equal to 50. Patients who are unable to walk because of paralysis or weakness, but who are up in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.
HEMATOLOGIC FUNCTION: Patients must have adequate bone marrow function, defined as a peripheral absolute neutrophil count of greater than or equal to 1,500/micro liter, and a platelet count of greater than or equal to 100,000/micro liter.
HEPATIC FUNCTION: Patients must have adequate liver function, defined as bilirubin less than 1.5 times the upper limit of normal, SGPT (ALT) and SGOT (AST) less than 2.5 times the upper limit of normal.
RENAL FUNCTION: Patients must have an age-adjusted normal serum creatinine OR a creatinine clearance greater than or equal to 60 mL/min/1.73 m2.
Age Maximum Serum Creatinine
Less than or equal to 5 0.8
Less than age 5 equal to less than 10 1.0
Less than age 10 equal to less than 15 1.2
Greater than 15 1.5
INFORMED CONSENT: All patients or their legal guardians (if the patient is less than 18 years old) must sign a document of informed consent (screening protocol) prior to performing studies to determine patient eligibility. After confirmation of patient eligibility all patients or their legal guardians must sign the protocol specific informed consent to document their understanding of the investigational nature and the risks of this study before any protocol related studies are performed (other than the studies which were performed to determine patient eligibility).
DURABLE POWER OF ATTORNEY (DPA): Patients who have brain tumors and who are 18 years of age will be offered the opportunity to assign a DPA so that another person can make decisions about their medical care if they become incapacitated or cognitively impaired.
BIRTH CONTROL: Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.
INCLUSION CRITERIA FOR EXPANDED COHORT OF LEUKEMIA PATIENTS
(APPENDIX 1):
AGE: Patients must be greater than or equal to 12 months and less than or equal to 21 years of age.
DIAGNOSIS: Patients must have a diagnosis of relapsed or refractory leukemia.
DISEASE STATUS: Patients with refractory or second or greater relapsed leukemia must have greater than 25 percent blasts in the bone marrow (M3 bone marrow). Active extramedullary disease (except for leptomeningeal disease) may also be present.
THERAPEUTIC OPTIONS: Patients' current disease state must be one that has relapsed after or failed to respond to frontline curative therapy and there must not be other potentially curative treatment options available. Curative therapy may include surgery, radiation therapy, chemotherapy, or any combination of these modalities.
PRIOR THERAPY: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
-Myelosuppressive chemotherapy or monocolonal antibody treatment: Patients must have had their last dose of chemotherapy at least two weeks prior to study entry. Patients with acute promyelocytic leukemias (APL) must be refractory to treatment with retinoic acid and arsenic trioxide. Patients with Philadelphia (Ph) chromosome positive CML must be refractory to imatinab (Gleevac™ (Trademark)). Patients must not have received treatment with a monocolonal antibody within 3 weeks of entry onto this study.
-Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor with the exception of erythropoietin.
-Biologic (anti-neoplastic agent): At least 7 days since of the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
-Steroid Therapy: Must be on a stable or tapering dose of corticosteroids for 7 days prior to enrollment on this study.
-Radiation Therapy: greater than or equal to 2 weeks for local palliative XRT; greater than or equal to 3 months must have elapsed if prior to TBI, craniospinal XRT, or greater than or equal to 50 percent of radiation of pelvis; greater than or equal to 6weeks must have elapsed if other substantial bone marrow radiation.
-Stem Cell Transplant or Rescue: No evidence of acute graft vs. host disease and greater than or equal to 2 months must have elapsed.
PERFORMANCE STATUS: Patients greater than 10 years must have a Karnofsky performance level greater than or equal to 50, and children less than or equal to 10 years must have a Lansky performance of greater than or equal to 50 (See Appendix 1A).
HEMATOLOGIC FUNCTION: Patient's must have a platelet count greater than or equal to 20,000/microL (may receive platelet transfusions) and Hemoglobin of greater than or equal to 8.0 gm/dL (may receive RBC transfusions).
HEPATIC FUNCTION: Patients must have adequate liver function defined as bilirubin less than 1.5 times the upper limit of normal , SGPT (ALT) and SGOT (AST) less than 2.5 times the upper limit of normal.
RENAL FUNCTION: Patients must have an age-adjusted normal serum creatinine (see Table below) OR a creatinine clearance of greater than or equal to 60 mL/min/1.73 m(2).
Age Maximum Serum Creatinine
Less than or equal to 5 0.8
Less than age 5 equal to less than 10 1.0
Less than age 10 equal to less than 15 1.2
Greater than 15 1.5
INFORMED CONSENT: All patients or their legal guardians (if the patient is less than 18 years old) must sign a document of informed consent (screening protocol) prior to performing studies to determine patient eligibility. After confirmation of patient eligibility all patients or their legal guardians must sign the protocol specific informed consent to document their understanding of the investigational nature and the risks of this study before any protocol related studies are performed (other than the studies which were performed to determine patient eligibility).
DURABLE POWER OF ATTORNEY (DPA): Patients who are 18 years of age will be offered the opportunity to assign a DPA so that another person can make decisions about their medical care if they become incapacitated or cognitively impaired.
BIRTH CONTROL: Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.
EXCLUSION CRITERIA FOR REFRACTORY SOLID TUMORS AND LEUKEMIAS:
-Clinically significant unrelated systemic illness, such as serious infections, hepatic, renal or other organ dysfunction, which in the judgment of the Principal or Associate Investigators of this protocol would compromise the patient's ability to tolerate the investigational agent or are likely to interfere with the study procedures or results.
-Pregnant or breast feeding females are excluded because BMS-247550 may be harmful to the developing fetus or nursing child.
-Patients currently receiving other investigational agents.
-Patients currently receiving St. John Wort. The intake of other agents inducing CYP3A4 is not prohibited (list provided in Section 8.1.10).
-Patients receiving known inhibitors of CYP3A4 including grapefruit juice within 1 week prior to and following the administration of BMS-247550 (inhibitors of CYP3A4 are listed in Section 8.1.10).
-Patients with preexisting grade 2 or greater sensory neuropathy.
-Patients with known severe prior hypersensitivity reaction to agents containing Cremophor EL.
-For patients with solid tumors only: Patients with a history of bone marrow transplantation within the previous 6 months or extensive radiotherapy (craniospinal radiation, total body radiation, or radiation to more than half of the pelvis).
-For patients with leukemia only: Patients with active CNS leukemia (CNS3).
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009