phase i/ii trial of r-chop + azacytidine in diffuse large b cell lymphoma

Conditions: Diffuse Large B Cell Lymphoma

Summary: this is a phase i/ii open label, multi-center study of azacytidine in combination with standard rchop therapy in patients with dlbcl. patients will be treated with azacytidine at escalating doses on days 1-5, followed by standard dose rituximab plus chop chemotherapy on day 8, every 21 days. patients will be treated for a total 6 cycles. the phase ii portion will then evaluate efficacy of the combination at the established mtd.


Eligibility criteria:
inclusion criteria: * patients must have histologically confirmed dlbcl with characteristic immunophenotypic profiles. tumor tissue must be confirmed to express the cd20 antigen by flow cytometry or immunohistochemistry. * patients must have at least one site of measurable disease, 1.5 cm in diameter or greater. * patient has not had any previous treatment. * stage ii (not appropriate for abbreviated chemoimmunotherapy and radiotherapy), iii or iv disease * able to adhere to the study visit schedule and other protocol requirements. * patients must have laboratory test results within these ranges: * absolute neutrophil count \> = 1500/mm³ * platelet count \> = 75,000/mm³ * serum creatinine \< = 1.5x upper limit of normal (uln) * total bilirubin \< = 1.5x uln. higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis. * ast (sgot) and alt (sgpt) \< = 2 x uln * disease free of prior malignancies for \> = 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. * women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment. * women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with azacitidine. the effects of azacytidine on the developing human fetus at the recommended therapeutic dose are unknown. for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * age \>18 years. * ability to understand and the willingness to sign a written informed consent document. * ecog performance status of 0-2 exclusion criteria: * patients must not have any serious medical condition, laboratory abnormality,or psychiatric illness that would prevent the subject from signing the informed consent form. * patients must not have any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * use of any other experimental drug or therapy within 28 days of baseline. * concurrent use of other anti-cancer agents or treatments. * known positive for hiv or infectious hepatitis b. * known central nervous system involvement by lymphoma. * known or suspected hypersensitivity to azacitidine or mannitol. * patients must not have advanced malignant hepatic tumors. * pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.