title: A multicenter, open-label phase II study of recombinant CPT (Circularly Permuted TRAIL) plus thalidomide in patients with relapsed and refractory multiple myeloma.
abstract: Circularly permuted TRAIL (CPT), a recombinant mutant of human Apo2L/TRAIL, is a novel antitumor candidate for multiple myeloma (MM) and other hematologic malignancies. In this phase II study, the safety and efficacy of CPT plus thalidomide was investigated in thalidomide-resistant MM patients. A total of 43 patients were recruited into three CPT plus thalidomide cohorts based on CPT dosage in sequence: 5 mg/kg (n = 11), 8 mg/kg (n = 17), and 10 mg/kg (n = 15). CPT was administered via intravenous infusion on days 1-5, and thalidomide was given orally at 100 mg once daily in each 21-day cycle. The overall response rate (ORR) of 41 efficacy-evaluable patients was 22.0% (2 complete response, 3 near complete response, and 4 partial response). No significant difference in the ORR was observed among the three dose cohorts; however, the ORR tended to be higher with the higher-dose regimen. Median progression-free survival and median duration of response were 6.6 months and 6.1 months, respectively. The most common treatment-related adverse events (TRAEs) were neutropenia (46.5%), leukopenia (41.9%), fever (37.2%), elevated AST (32.6%), and elevated ALT (20.9%). TRAEs of Grade 3-4 were mainly neutropenia (18.6%), anemia (9.3%), elevated AST (7.0%), and leukopenia (4.7%). No significant differences were found in the incidence and severity of TRAEs among the three cohorts. In conclusion, CPT plus thalidomide was well tolerated with no occurrence of dose-limiting toxicities and demonstrated promising antitumor activity in RRMM patients. CPT at 10 mg/kg for 5 days in combination with thalidomide and dexamethason will be studied in the next clinical trial.
authors.affiliation: Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
authors.forename: Chuanying
authors.initials: C
authors.lastname: Geng
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
authors.forename: Yaozhong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ke
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.forename: Lugui
authors.initials: L
authors.lastname: Qiu
authors.forename: Hao
authors.initials: H
authors.lastname: Xi
authors.forename: Fuxu
authors.initials: F
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Shifang
authors.initials: S
authors.lastname: Yang
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zheng
authors.forename: Zhongxia
authors.initials: Z
authors.lastname: Huang
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007970:Leukopenia / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D016879:Salvage Therapy; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage / Q000009:adverse effects; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D013792:Thalidomide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase