Tags

Type your tag names separated by a space and hit enter

Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma.
J Clin Oncol 2010; 28(9):1591-8JC

Abstract

PURPOSE

KW-0761, a defucosylated humanized anti-CC chemokine receptor 4 (CCR4) antibody, exerts a strong antibody-dependent cellular cytotoxic effect. This phase I study assessed the safety, pharmacokinetics, recommended phase II dose and efficacy of KW-0761 in patients with relapsed CCR4-positive adult T-cell leukemia-lymphoma (ATL) or peripheral T-cell lymphoma (PTCL).

PATIENTS AND METHODS

Sixteen patients received KW-0761 once a week for 4 weeks by intravenous infusion. Doses were escalated, starting at 0.01, 0.1, 0.5, and finally 1.0 mg/kg by a 3 + 3 design.

RESULTS

Fifteen patients completed the protocol treatment. Only one patient, at the 1.0 mg/kg dose, developed grade 3 dose-limiting toxicities, skin rash, and febrile neutropenia, and grade 4 neutropenia. Other treatment-related grade 3 to 4 toxicities were lymphopenia (n = 10), neutropenia (n = 3), leukopenia (n = 2), herpes zoster (n = 1), and acute infusion reaction/cytokine release syndrome (n = 1). Neither the frequency nor severity of toxicities increased with dose escalation. The maximum tolerated dose was not reached. Therefore, the recommended phase II dose was determined to be 1.0 mg/kg. No patients had detectable levels of anti-KW-0761 antibody. The plasma maximum and trough, and the area under the curve of 0 to 7 days of KW-0761, tended to increase dose and frequency dependently. Five patients (31%; 95% CI, 11% to 59%) achieved objective responses: two complete (0.1; 1.0 mg/kg) and three partial (0.01; 2 at 1.0 mg/kg) responses.

CONCLUSION

KW-0761 was tolerated at all the dose levels tested, demonstrating potential efficacy against relapsed CCR4-positive ATL or PTCL. Subsequent phase II studies at the 1.0 mg/kg dose are thus warranted.

Authors+Show Affiliations

Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Aichi, Japan. kyamamoto@aichi-cc.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Multicenter Study

Language

eng

PubMed ID

20177026

Citation

Yamamoto, Kazuhito, et al. "Phase I Study of KW-0761, a Defucosylated Humanized anti-CCR4 Antibody, in Relapsed Patients With Adult T-cell Leukemia-lymphoma and Peripheral T-cell Lymphoma." Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 28, no. 9, 2010, pp. 1591-8.
Yamamoto K, Utsunomiya A, Tobinai K, et al. Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol. 2010;28(9):1591-8.
Yamamoto, K., Utsunomiya, A., Tobinai, K., Tsukasaki, K., Uike, N., Uozumi, K., ... Ueda, R. (2010). Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 28(9), pp. 1591-8. doi:10.1200/JCO.2009.25.3575.
Yamamoto K, et al. Phase I Study of KW-0761, a Defucosylated Humanized anti-CCR4 Antibody, in Relapsed Patients With Adult T-cell Leukemia-lymphoma and Peripheral T-cell Lymphoma. J Clin Oncol. 2010 Mar 20;28(9):1591-8. PubMed PMID: 20177026.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. AU - Yamamoto,Kazuhito, AU - Utsunomiya,Atae, AU - Tobinai,Kensei, AU - Tsukasaki,Kunihiro, AU - Uike,Naokuni, AU - Uozumi,Kimiharu, AU - Yamaguchi,Kazunari, AU - Yamada,Yasuaki, AU - Hanada,Shuichi, AU - Tamura,Kazuo, AU - Nakamura,Shigeo, AU - Inagaki,Hiroshi, AU - Ohshima,Koichi, AU - Kiyoi,Hitoshi, AU - Ishida,Takashi, AU - Matsushima,Kouji, AU - Akinaga,Shiro, AU - Ogura,Michinori, AU - Tomonaga,Masao, AU - Ueda,Ryuzo, Y1 - 2010/02/22/ PY - 2010/2/24/entrez PY - 2010/2/24/pubmed PY - 2010/5/5/medline SP - 1591 EP - 8 JF - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JO - J. Clin. Oncol. VL - 28 IS - 9 N2 - PURPOSE: KW-0761, a defucosylated humanized anti-CC chemokine receptor 4 (CCR4) antibody, exerts a strong antibody-dependent cellular cytotoxic effect. This phase I study assessed the safety, pharmacokinetics, recommended phase II dose and efficacy of KW-0761 in patients with relapsed CCR4-positive adult T-cell leukemia-lymphoma (ATL) or peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: Sixteen patients received KW-0761 once a week for 4 weeks by intravenous infusion. Doses were escalated, starting at 0.01, 0.1, 0.5, and finally 1.0 mg/kg by a 3 + 3 design. RESULTS: Fifteen patients completed the protocol treatment. Only one patient, at the 1.0 mg/kg dose, developed grade 3 dose-limiting toxicities, skin rash, and febrile neutropenia, and grade 4 neutropenia. Other treatment-related grade 3 to 4 toxicities were lymphopenia (n = 10), neutropenia (n = 3), leukopenia (n = 2), herpes zoster (n = 1), and acute infusion reaction/cytokine release syndrome (n = 1). Neither the frequency nor severity of toxicities increased with dose escalation. The maximum tolerated dose was not reached. Therefore, the recommended phase II dose was determined to be 1.0 mg/kg. No patients had detectable levels of anti-KW-0761 antibody. The plasma maximum and trough, and the area under the curve of 0 to 7 days of KW-0761, tended to increase dose and frequency dependently. Five patients (31%; 95% CI, 11% to 59%) achieved objective responses: two complete (0.1; 1.0 mg/kg) and three partial (0.01; 2 at 1.0 mg/kg) responses. CONCLUSION: KW-0761 was tolerated at all the dose levels tested, demonstrating potential efficacy against relapsed CCR4-positive ATL or PTCL. Subsequent phase II studies at the 1.0 mg/kg dose are thus warranted. SN - 1527-7755 UR - https://www.unboundmedicine.com/medline/citation/20177026/Phase_I_study_of_KW_0761_a_defucosylated_humanized_anti_CCR4_antibody_in_relapsed_patients_with_adult_T_cell_leukemia_lymphoma_and_peripheral_T_cell_lymphoma_ L2 - http://ascopubs.org/doi/full/10.1200/JCO.2009.25.3575?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -