A Phase I Study of Indenoisoquinolines LMP400 and LMP776 in Adults With Relapsed Solid Tumors and Lymphomas

Background: * Indenoisoquinolines are non-camptothecin inhibitors of topoisomerase 1 (top1) with improved characteristics over their predecessors. Indenoisoquinolines have better chemical stability, producing stable DNA-top1 cleavage complexes, and exhibit a preference for unique DNA cleavage sites, compared with their camptothecin counterparts. * They have demonstrated activity against camptothecin-resistant cell lines and produce DNA-protein crosslinks, which are resistant to reversal. They also show less or no resistance to cells overexpressing the ATP-binding cassette (ABC) transporters, ABCG2, and multidrug resistance (MDR-1). Primary Objectives: * Define the maximum tolerated dose (MTD) of LMP400 (NSC 743400) and LMP776 (NSC 725776) administered intravenously (IV) daily for 5 days (QDx5). * Define the dose-limiting toxicities (DLTs) and toxicity profile associated with administration of LMP400 and LMP776. * Evaluate the effect of LMP400 and LMP776 on the pharmacodynamic (PD) endpoint, gamma-H2AX, in tumor biopsy pre- and post-treatment. In particular, compare the PD response, defined as the mean percent nuclear area that is gamma-H2AX positive (%NAP) in tumor biopsies, at the MTD for LMP400 and LMP776, and the toxicity profile versus PD dose-response relationship. Secondary Objectives: * Obtain preliminary evidence of anti-tumor activity of LMP400 and LMP776. * Characterize the pharmacokinetic (PK) profile of LMP400 and LMP776. Eligibility: -Adult patients must have histologically confirmed relapsed solid tumor malignancy or lymphoma that is metastatic or unresectable for which standard curative measures do not exist or are associated with minimal patient survival benefit. Study Design: * Cycle 1 and subsequent cycles: Patients will be randomized to receive either LMP400 or LMP776 administered IV QD over 1 hour on days 1-5 followed by 23 days without drug (28-day cycle). * PK and PD samples will be collected in cycle 1 only. Tumor biopsies will not be collected during the escalation phase; however, tumor biopsies will be mandatory during the expansion phase.