a phase 1 study evaluating cpi-0610 in patients with progressive lymphoma

Conditions: Lymphoma

Summary: first in human, open-label, sequential dose escalation and expansion study of cpi-0610 in patients with progressive lymphoma. cpi-0610 is a small molecule inhibitor of bromodomain and extra-terminal (bet) proteins.


Eligibility criteria:
inclusion criteria: * adults (aged ≥ 18 years) * histologically confirmed diagnosis of a non-hodgkin or hodgkin lymphoma that has progressed in spite of prior treatment, and for which additional effective standard therapy is not available * patients may have either measurable or non-measurable disease, but in all cases eligible patients must have disease that can be clinically evaluated for improvement or progression * eastern cooperative oncology group (ecog) performance status ≤2 * adequate hematological, renal, hepatic, and coagulation laboratory assessments * written informed consent to participate in this study before the performance of any study-related procedure exclusion criteria: * a primary lymphoma of the central nervous system (cns) or known lymphomatous involvement of the cns. cns imaging and cerebrospinal fluid sampling are not mandatory in the absence of a clinical suspicion of lymphomatous involvement of the cns. * current infection with hiv, hepatitis b or hepatitis c. patients will have serologic testing performed during screening for hiv and hepatitis b and c. any serologic results suggestive of an ongoing viral infection will be further investigated as necessary to clarify the patient's status. * impairment of gastrointestinal (gi) function or gi disease that may significantly alter the absorption of cpi-0610, including any unresolved nausea, vomiting, or diarrhea that is ctcae grade \>1. * impaired cardiac function or clinically significant cardiac diseases, including any of the following: * acute myocardial infarction or angina pectoris ≤ 6 months prior to starting study drug * serum cardiac troponin (ctn) level ≥ 99% percentile of the upper reference limit * qtcf \> 470 msec on the screening ecg * left ventricular ejection fraction (lvef) \< 40% * uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded.) * any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection) * systemic anti-cancer treatment or radiotherapy less than 2 weeks before the first dose of cpi-0610 * radioimmunotherapy (e.g., 131i-tositumomab, 90y-ibritumomab tiuxetan) less than 6 weeks before the first dose of cpi-0610 * treatment with an investigational small molecule less than 2 weeks before the first dose of cpi-0610. in addition, the first dose of cpi-0610 should not occur before a period equal to or greater than 5 half-lives of the small molecule investigational agent has elapsed. * treatment with a therapeutic antibody less than 4 weeks before the first dose of cpi-0610. a minimum 2-week period between the last treatment with a therapeutic antibody and the first dose of cpi-0610 may be permitted in patients with rapidly progressive or aggressive subtypes of lymphoma following discussion with the medical monitor. * treatment with medications that are known to be strong inhibitors or inducers of cyp450 enzymes. * treatment with medications that are known to carry a risk of torsades de pointes. * immunosuppressive treatment that cannot be discontinued both prior to study entry and for the duration of the study. oral prednisone at a dose of 10 mg or less per day is allowed, as are other oral corticosteroids given at glucocorticoid-equivalent doses. topical, nasal and inhaled corticosteroids are also allowed. * pregnant or lactating women * women of child-bearing potential and men with reproductive potential, if they are unwilling to use adequate contraception while on study therapy and for 3 months thereafter * patients unwilling or unable to comply with this study protocol

Keywords: phase 1 oncology bet inhibitor