Lymphoma, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, small intestine lymphoma, unspecified adult solid tumor, protocol specific, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III adult Burkitt lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, recurrent adult T-cell leukemia/lymphoma, primary central nervous system non-Hodgkin lymphoma, intraocular lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent mantle cell lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage III marginal zone 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
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of azacitidine plus phenylbutyrate in treating patients with advanced or metastatic solid tumors that have not responded to previous treatment.
Detailed description
OBJECTIVES: * Evaluate the safety and toxicity of azacitidine plus phenylbutyrate in patients with refractory solid tumors. * Determine the maximum tolerated dose of this treatment regimen where maximal gene reexpression occurs in these patients. * Evaluate the pharmacokinetics of these drugs in these patients. * Determine the minimally effective dose of azacitidine in combination with phenylbutyrate that elicits a biological or clinical response in these patients. OUTLINE: This is a dose escalation study. Patients receive azacitidine subcutaneously for 14-21 days and sodium phenylbutyrate IV continuously for 1-7 days. Treatment repeats every 35 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses and durations of treatment with azacitidine and phenylbutyrate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities. PROJECTED ACCRUAL: Approximately 3-50 patients will be accrued for this study within 12-18 months.
Interventions
subcutaneous injection (SC)
DRUGsodium phenylbutyrate
continuous intravenous (CIV)
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor not amenable to curative therapy * Lymphoma allowed * Progressive disease * Evaluable disease * No CNS metastases by CT scan or MRI PATIENT CHARACTERISTICS: Age: * 18 and over Performance status: * ECOG 0-2 Life expectancy: * Not specified Hematopoietic: * Hemoglobin at least 8 g/dL (may be achieved by transfusion) * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic: * Bilirubin no greater than 2 mg/dL (unless due to hemolysis or Gilbert's syndrome) * SGOT and SGPT less than 2 times upper limit of normal Renal: * Creatinine no greater than 2.0 mg/dL Other: * No active infection * HIV negative * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception for 2 weeks before, during, and 3 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * At least 4 weeks since prior adjuvant chemotherapy for advanced or metastatic disease and recovered Endocrine therapy: * Not specified Radiotherapy: * At least 4 weeks since prior radiotherapy and recovered Surgery: * Not specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimal Effective Dose (MED) of Azacitidine with Phenylbutyrate | up to 6 months | MED (milligrams) of combined Azacitidine and Phenylbutyrate that results in clinical response, as defined by Standard World Health Organization (WHO) criteria and/or target inhibition. |
Secondary
| Measure | Time frame |
|---|---|
| Toxicity as assessed by number of participants experiencing adverse events Grade 3 or higher as defined by CTCAE v2.0 | up to 6 months |
| Pharmacokinetics of Azacitidine combined with Phenylbutyrate as measured by maximal plasma concentration (Cmax) | Up to 24 hours |
| Gene-re-expression of epigenetic modulation in Peripheral Blood Mononuclear Cells (PBMC) as measured by change in Epstein-Barr Virus (EBV) viral load (number of copies per 1 million cells) after treatment with Azacitidine | Change from baseline to up to 6 months |
Countries
United States
Outcome results
None listed