Ixabepilone in Treating Young Patients With Solid Tumors or Leukemia That Haven't Responded to Therapy

• Status: Completed
• Trial end date: 2010-04-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of ixabepilone in treating young patients with relapsed or refractory solid tumors or leukemia.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborator: National Cancer Institute (NCI)
• Treatments: Epothilones

Criteria

DISEASE CHARACTERISTICS:

• Meets 1 of the following criteria:

• Histologically confirmed solid tumor (closed to accrual as of 10/4/2007) that relapsed after or failed to respond to front-line curative therapy and for which no other potentially curative treatment options exist

• Curative therapy may include surgery, radiotherapy, chemotherapy, or any combination of these modalities

• Eligible tumor types include, but are not limited to, the following:

• Rhabdomyosarcoma

• Other soft tissue sarcomas

• Ewing's sarcoma family of tumors

• Osteosarcoma

• Neuroblastoma

• Wilms' tumor

• Hepatic tumors

• Germ cell tumors

• Primary brain tumors

• Histologic confirmation may be waived for brain stem or optic glioma

• Diagnosis of relapsed or refractory leukemia

• Patients with refractory or second or greater relapsed leukemia must have > 25% blasts in the bone marrow (M3 bone marrow) with or without active extramedullary disease (except for leptomeningeal disease)

• Relapsed after or failed to respond to frontline curative therapy and no other potentially curative therapy (e.g., radiotherapy, chemotherapy, or any combination of these modalities) exists

• Patients with acute promyelocytic leukemia must be refractory to treatment with retinoic acid and arsenic trioxide

• Patients with Philadelphia chromosome positive chronic myelogenous leukemia must be refractory to imatinib

• No active CNS leukemia (CNS3)

PATIENT CHARACTERISTICS:

Age:

• 2 to 18 (solid tumor patients [closed to accrual as of 10/4/2007])

• 1 to 21 (leukemia patients)

Performance status:

• For patients age 11 to 21:

• Karnofsky 50-100%

• For patients age 1 to 10:

• Lansky 50-100%

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count at least 100,000/mm^3 (20,000/mm^3 for leukemia patients)

• Hemoglobin ≥ 8.0 g/dL

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)

• SGOT and SGPT less than 2.5 times ULN

• No hepatic dysfunction that would preclude study

Renal:

• Creatinine normal for age OR

• Creatinine clearance at least 60 mL/min

• No renal dysfunction that would preclude study

Other:

• No known severe prior hypersensitivity reaction to agents containing Cremophor EL

• No clinically significant unrelated systemic illness (e.g., serious infections or other organ dysfunction) that would preclude study

• No grade 2 or greater preexisting sensory neuropathy

• More than 2 month since prior and no concurrent evidence of graft vs host disease

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Recovered from all therapy-related acute toxic effects (leukemia patients only)

• Prior epoetin alfa allowed

• At least 3 days since other prior colony-stimulating factors (e.g., filgrastim (G-CSF), sargramostim (GM-CSF), or interleukin-11 (IL-11))

• At least 6 months since prior bone marrow transplantation

• At least 2 months since prior stem cell transplantation or rescue (leukemia patients)

• At least 7 days since prior therapy with a biological agent and hematopoietic growth factor with the exception of erythropoietin

• More than 3 weeks since prior monoclonal antibody therapy (leukemia patients only)

• No concurrent GM-CSF or IL-11

• No concurrent immunotherapy

Chemotherapy:

• See Disease Characteristics

• Recovered from all therapy-related acute toxic effects (leukemia patients only)

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)

• No other concurrent anticancer chemotherapy

Endocrine therapy:

• Concurrent corticosteroids allowed for the control of symptoms related to tumor-associated edema in patients with brain tumors

• Patients with brain tumors must be on a stable or tapering dose of corticosteroids for 7 days before baseline scan is performed for the purpose of assessing response to study therapy

• Must be on a stable or tapering dose of corticosteroids for 7 days prior to study entry (leukemia patients only)

Radiotherapy:

• See Disease Characteristics

• Recovered from all therapy-related acute toxic effects (leukemia patients only)

• At least 4 weeks since prior radiotherapy

• More than 2 weeks since prior local palliative radiotherapy (leukemia patients only)

• More than 3 months since prior total-body irradiation, craniospinal radiotherapy, or radiotherapy to ≥50% of the pelvis (leukemia patients only)

• More than 6 weeks since prior other substantial bone marrow radiotherapy (leukemia patients only)

• No prior extensive radiotherapy (e.g., craniospinal irradiation, total body irradiation, or radiotherapy to more than half of the pelvis)

• No concurrent anticancer radiotherapy

Surgery:

• See Disease Characteristics

Other:

• Recovered from prior therapy

• At least 30 days since any prior investigational anticancer therapy

• At least 1 week since prior known inhibitors of CYP3A4, including any of the following:

• Antibiotics (i.e., clarithromycin, erythromycin, or troleandomycin)

• Anti-HIV agents (i.e, delaviridine, nelfinavir, amprenavir, ritonavir, idinavir, saquinavir, or lopinavir)

• Anti-fungals (i.e., itraconazole, ketoconazole, fluconazole [doses > 3mg/kg/day], or voriconazole)

• Anti-depressants (i.e., nefaxodone or fluovoxamine)

• Calcium channel blockers (i.e., verapamil or diltiazem)

• Anti-emetics (i.e., aprepitant [Emend®])

• Miscellaneous agents (i.e., amiodarone)

• Grapefruit juice

• No other concurrent investigational agents

• No concurrent St. John's Wort

• No concurrent known inhibitors of CYP3A4, including grapefruit juice

• Concurrent other agents inducing CYP3A4 allowed