Effectiveness and Safety of Therapy Based on Attenuated ATO Plus Low-Dose ATRA in Patients With APL

Summary

ATRA is the standard of care for all patients with APL. The use of lower doses of ATRA has been shown since the 1990s to achieve therapeutic efficacy with doses of 25mg/m2/day. ATO demonstrated considerable effectiveness in this disease. More recently, an attenuated regimen has been proven to be effective. In this study we intent to demonstrate the effectiveness of combined therapy of low-dose ATRA plus attenuated dose ATO.

Timeline

Start

2022-07-01

Primary completion

2025-06-30

Completion

2025-07-31

Publications

• Background Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567-72.
• Background Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, Shen ZX, Sun GL, Ma J, Zhang P, Zhang TD, Gazin C, Naoe T, Chen SJ, Wang ZY, Chen Z. In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood. 1996 Aug 1;88(3):1052-61.
• Background Castaigne S, Lefebvre P, Chomienne C, Suc E, Rigal-Huguet F, Gardin C, Delmer A, Archimbaud E, Tilly H, Janvier M, et al. Effectiveness and pharmacokinetics of low-dose all-trans retinoic acid (25 mg/m2) in acute promyelocytic leukemia. Blood. 1993 Dec 15;82(12):3560-3.
• Background Chen GQ, Shen ZX, Wu F, Han JY, Miao JM, Zhong HJ, Li XS, Zhao JQ, Zhu J, Fang ZW, Chen SJ, Chen Z, Wang ZY. Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Leukemia. 1996 May;10(5):825-8.
• Background Jaime-Perez JC, Gonzalez-Leal XJ, Pinzon-Uresti MA, Gomez-De Leon A, Cantu-Rodriguez OG, Gutierrez-Aguirre H, Gomez-Almaguer D. Is There Still a Role for Low-Dose All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia in the Arsenic Trioxide Era? Clin Lymphoma Myeloma Leuk. 2015 Dec;15(12):816-9. doi: 10.1016/j.clml.2015.09.002. Epub 2015 Sep 25.
• Background Burnett AK, Russell NH, Hills RK, Bowen D, Kell J, Knapper S, Morgan YG, Lok J, Grech A, Jones G, Khwaja A, Friis L, McMullin MF, Hunter A, Clark RE, Grimwade D; UK National Cancer Research Institute Acute Myeloid Leukaemia Working Group. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Oct;16(13):1295-305. doi: 10.1016/S1470-2045(15)00193-X. Epub 2015 Sep 14.

Drugs

Indications