Perifosine in Treating Patients With Refractory Solid Tumors or Hematologic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of perifosine in treating patients who have refractory solid tumors or hematologic cancer.

Detailed Description
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OBJECTIVES: Determine the dose-limiting toxicity and maximum tolerated dose of perifosine administered as a varying series of loading and maintenance doses in patients with refractory solid tumors, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, myelodysplastic syndromes, or Hodgkin's lymphoma. Determine the profile of adverse reactions (including changes in laboratory parameters) in patients treated with this regimen. Determine any disease responses that may occur in patients treated with this regimen. Determine the steady-state pharmacology and pharmacokinetics of this regimen in these patients. OUTLINE: This is a dose-escalation study. Patients receive a loading dose of oral perifosine on day 1 followed by a maintenance dose 2-3 times daily beginning on day 2 or 3 and continuing until day 21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating loading and maintenance doses of perifosine until the maximum tolerated dose (MTD) of each 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. Once the MTD is determined, an additional 10 patients are treated at that dose level. Patients are followed every 3 months. PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study within 12-18 months.

Official Title
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A Phase I Trial of Oral Perifosine With Different Loading Schedules in Patients With Refractory Neoplasms

Conditions
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Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: perifosine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed solid tumor, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, myelodysplastic syndromes, or Hodgkin's lymphoma that has no effective standard therapeutic option but requires systemic therapy No history of CNS neoplasms For prostate cancer: Tumor progression during blockade of testicular and adrenal androgens At least 4 weeks since prior flutamide or other antiandrogens without disease improvement Leuprolide or other gonadotropin-releasing hormones should be maintained in patients without an orchiectomy Testosterone in the castrate range For breast cancer: At least 4 weeks since any prior hormonal therapy with evidence of disease progression PATIENT CHARACTERISTICS: Age: Over 18 Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Platelet count greater than 50,000/mm^3 Absolute granulocyte count greater than 500/mm^3 Hemoglobin at least 9.0 g/dL Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT and SGPT no greater than 2.5 times normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No history of unstable or newly diagnosed angina pectoris No myocardial infarction within the past 6 months No New York Heart Association class II-IV heart disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No recent acute or chronic gastrointestinal conditions (e.g., stomach ulcer or enteritis) that might affect tolerability or drug absorption No allergic reaction to any medication with a structure similar to perifosine No pre-existing retinal disease or pathologic baseline electrooculogram No cataracts that would interfere with normal vision or require medical intervention No other serious concurrent illness that would preclude assessment of drug effect PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered At least 2 months since prior UCN-01 More than 3 months since prior suramin Endocrine therapy: See Disease Characteristics No concurrent corticosteroids except for physiological replacement or as antiemetics Radiotherapy: At least 4 weeks since prior radiotherapy (6 weeks for bone-seeking radioisotopes) and recovered Surgery: See Disease Characteristics Other: No other concurrent antineoplastic therapies

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: perifosine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, unspecified adult solid tumor, protocol specific, previously treated myelodysplastic syndromes, de novo myelodysplastic syndromes, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, secondary myelodysplastic syndromes, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult Burkitt lymphoma, stage IV adult Hodgkin lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma