Indenoisoquinoline LMP744 in Adults With Relapsed Solid Tumors and Lymphomas

Summary

Background: The new drug LMP744 (NSC 706744) damages deoxyribonucleic acid (DNA). This causes cell death. Researchers want to see if it can treat certain kinds of cancer. They want to understand how the drug works and how it affects the body. Objective: To test the safety of LMP744 and find out the dose of the drug that can be safely given to humans. Eligibility: Adults at least 18 years old who have metastatic solid tumors or lymphoma, which have progressed after other treatment. Design: Participants will be screened with: * Vital signs taken * Blood and urine tests * Heart tests * Scans or ultrasound Some participants will have a tumor sample taken 2 times. A small piece of tumor is removed by a small needle. A scan or ultrasound will guide the process. The study will be done in 28-day cycles. Each cycle, participants will get the study drug in a vein for 60 minutes once a day for 5 days. For day 1 of cycle 1, participants will be admitted to the clinic and have blood and urine taken several times. At the beginning of each cycle, participants will have a clinic visit and repeat some screening tests. They will also do this twice in the middle of cycle 1 and once in the middle of cycle 2. After participants stop taking the study drug, they will be followed for 30 days. They may give blood samples. They will be contacted by phone to see how they are doing....

Timeline

Start

2017-02-27

Primary completion

2023-10-02

Completion

2023-10-12

Publications

• Background Antony S, Kohlhagen G, Agama K, Jayaraman M, Cao S, Durrani FA, Rustum YM, Cushman M, Pommier Y. Cellular topoisomerase I inhibition and antiproliferative activity by MJ-III-65 (NSC 706744), an indenoisoquinoline topoisomerase I poison. Mol Pharmacol. 2005 Feb;67(2):523-30. doi: 10.1124/mol.104.003889. Epub 2004 Nov 5.
• Background Antony S, Agama KK, Miao ZH, Takagi K, Wright MH, Robles AI, Varticovski L, Nagarajan M, Morrell A, Cushman M, Pommier Y. Novel indenoisoquinolines NSC 725776 and NSC 724998 produce persistent topoisomerase I cleavage complexes and overcome multidrug resistance. Cancer Res. 2007 Nov 1;67(21):10397-405. doi: 10.1158/0008-5472.CAN-07-0938.
• Background Meng LH, Liao ZY, Pommier Y. Non-camptothecin DNA topoisomerase I inhibitors in cancer therapy. Curr Top Med Chem. 2003;3(3):305-20. doi: 10.2174/1568026033452546.
• O'Sullivan Coyne G, Kummar S, Rubinstein LV, Wilsker D, Moore N, Hogu M, Piekarz R, Covey J, Beumer JH, Ferry-Galow KV, Villaruz LC, Hollingshead MG, Holleran JL, Deppas JJ, Pommier Y, Ko B, Johnson BC, Parchhment RE, Ivy P, Doroshow JH, Chen AP. Phase 1 studies of the indenoisoquinolines LMP776 and LMP744 in patients with solid tumors and lymphomas. Cancer Chemother Pharmacol. 2025 May 29;95(1):58. doi: 10.1007/s00280-025-04778-5.

Drugs

Indications