bcx-1777 in treating patients with refractory cutaneous t-cell lymphoma

Conditions: Lymphoma

Summary: rationale: bcx-1777 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. purpose: phase i/ii trial to study the effectiveness bcx-1777 in treating patients who have refractory cutaneous t-cell lymphoma.

objectives: * determine the maximum tolerated dose of bcx-1777 in patients with refractory cutaneous t-cell lymphoma. * determine the efficacy of this drug in these patients. * determine the toxicity profile of this drug in these patients. * correlate plasma concentration of deoxyguanosine with clinical response and toxicity in patients treated with this drug. * determine the provisional optimal biological dose of this drug in these patients. outline: this is an open-label, nonrandomized, dose-escalation, multicenter study. * phase i: patients receive bcx-1777 iv over 30 minutes every 12 hours on days 1-5 (a total of 9 doses). treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of bcx-1777 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose at which no more than 2 of 6 patients experience dose-limiting toxicity. * phase ii: patients receive treatment as in phase i at the mtd of bcx-1777. patients (including those who respond to treatment) are followed at 14 and 30 days, monthly for 6 months, every 2 months for 6 months, and then every 6 months thereafter. projected accrual: a total of 3-64 patients (3-24 for phase i and 40 for phase ii) will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed cutaneous t-cell lymphoma (ctcl) * any stage except ia patch only * previously treated according to 1 of the following: * stage ia plaque, ib, or iia: * at least 4 prior conventional and/or experimental regimens (topical or systemic, including psoralen-ultraviolet light \[puva\] and systemic corticosteroids) * stage iib, iii, or iv: * at least 1 prior systemic regimen (systemic corticosteroids and puva do not count as systemic regimens for this purpose) note: repeated use of the same regimen is considered one regimen * measurable disease patient characteristics: age * 18 and over performance status * ecog 0-3 life expectancy * at least 3 months hematopoietic * granulocyte count at least 2,000/mm\^3 * platelet count at least 75,000/mm\^3 * hemoglobin at least 10.0 g/dl hepatic * bilirubin no greater than 1.5 times upper limit of normal (uln) (unless due to gilbert's syndrome) * alt no greater than 2 times uln * alkaline phosphatase no greater than 2 times uln * no hepatitis b or c renal * creatinine clearance at least 45 ml/min other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * hiv negative * human t-cell leukemia virus type 1 (htlv-1) negative * no other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * no other illness that would limit study participation * no active serious infection not controlled by antibiotics prior concurrent therapy: biologic therapy * no concurrent anticancer antibody therapy * no concurrent anticancer immunotherapy * no concurrent anticancer gene therapy * no concurrent anticancer vaccine therapy * no concurrent anticancer angiogenesis inhibitors * no concurrent sargramostim (gm-csf) * no concurrent filgrastim (g-csf) during course 1 of therapy chemotherapy * more than 21 days since prior chemotherapy unless fully recovered * no concurrent anticancer chemotherapy endocrine therapy * see disease characteristics * more than 2 weeks since prior topical corticosteroids * no concurrent anticancer hormonal therapy radiotherapy * more than 2 weeks since prior radiotherapy * no concurrent radiotherapy surgery * not specified other * more than 2 weeks since prior antineoplastic therapy * more than 21 days since prior investigational agents unless fully recovered * no concurrent citrate-blood products within 30 minutes before or after study treatment * no concurrent anticancer matrix metalloprotease inhibitors * no other concurrent anti-ctcl therapy * no concurrent use of tanning beds * no other concurrent investigational agents

Keywords: recurrent cutaneous t-cell non-hodgkin lymphoma stage i cutaneous t-cell non-hodgkin lymphoma stage ii cutaneous t-cell non-hodgkin lymphoma stage iii cutaneous t-cell non-hodgkin lymphoma stage iv cutaneous t-cell non-hodgkin lymphoma recurrent mycosis fungoides/sezary syndrome stage i mycosis fungoides/sezary syndrome stage ii mycosis fungoides/sezary syndrome stage iii mycosis fungoides/sezary syndrome stage iv mycosis fungoides/sezary syndrome