Neil D. Palmisiano, Ju-Whei Lee, David F. Claxton, Elisabeth M. Paietta, Hassan Alkhateeb, Jae Park, Nikolai A. Podoltsev, Ehab L. Atallah, Dale G. Schaar, Shira N. Dinner, Jonathan A. Webster, Selina M. Luger, Mark R. Litzow
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Here, we report the safety and efficacy outcomes of the phase I portion of this trial (NCT03504644).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>In a 3+3 dose escalation design, r/r ALL subjects were given single-agent VEN doses reaching 400, 600, or 800 mg for the three respective dose levels. Weekly L-VCR at 2.25 mg/m<sup>2</sup> IV was started on D15 of cycle 1. The primary phase I objective was to determine the maximum tolerated dose (MTD) of the combination.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Among the 18 patients in phase I, grade ≥ 3 treatment-related adverse events were reported in 89% of treated patients. Two patients (two of three) at dose level 3 experienced dose-limiting toxicities. Therefore, the MTD of the combination was determined to be dose level 2 (VEN 600 mg). Twenty-two percent of evaluable patients (<i>N</i> = 4) achieved a complete response, with two of them showing no evidence of measurable residual disease (MRD).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>The combination of VEN and L-VCR was found to be safe for patients with r/r ALL and encouraging preliminary efficacy, including MRD negative responses. With the removal of L-VCR from the US market, the phase 2 portion of this trial is actively enrolling with vincristine sulfate.</p>\n </section>\n </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 5","pages":"951-956"},"PeriodicalIF":0.0000,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.991","citationCount":"0","resultStr":"{\"title\":\"A phase 1 trial of venetoclax in combination with liposomal vincristine in patients with relapsed or refractory B-cell or T-cell acute lymphoblastic leukemia: Results from the ECOG-ACRIN EA9152 protocol\",\"authors\":\"Neil D. Palmisiano, Ju-Whei Lee, David F. Claxton, Elisabeth M. Paietta, Hassan Alkhateeb, Jae Park, Nikolai A. Podoltsev, Ehab L. Atallah, Dale G. Schaar, Shira N. Dinner, Jonathan A. Webster, Selina M. Luger, Mark R. 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引用次数: 0
摘要
复发或难治性(r/r)急性淋巴细胞白血病(ALL)或淋巴细胞淋巴瘤(LL)仍然是一项治疗难题。B-ALL和T-ALL的临床前数据表明,venetoclax(VEN)与长春新碱(VCR)具有协同作用。我们设计了一项I/II期试验(EA9152),将L-VCR和VEN联合用于r/r B或T细胞ALL或LL患者。在 3+3 剂量递增设计中,r/r ALL 受试者的单药 VEN 剂量分别达到 400、600 或 800 毫克。在第一周期的第15天开始每周静脉注射2.25毫克/平方米的L-VCR。I 期治疗的主要目的是确定联合用药的最大耐受剂量(MTD)。在 I 期治疗的 18 名患者中,89% 的患者报告了≥3 级的治疗相关不良事件。剂量为3级的两名患者(3人中有2人)出现了剂量限制性毒性。因此,联合用药的最大剂量被确定为剂量水平 2(VEN 600 毫克)。22%的可评估患者(N = 4)获得了完全应答,其中两名患者没有出现可测量的残留疾病(MRD)。随着 L-VCR 退出美国市场,该试验的 2 期部分正在积极招募硫酸长春新碱患者。
A phase 1 trial of venetoclax in combination with liposomal vincristine in patients with relapsed or refractory B-cell or T-cell acute lymphoblastic leukemia: Results from the ECOG-ACRIN EA9152 protocol
Introduction
Relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) remains a therapeutic challenge. Preclinical data in both B- and T-ALL suggests synergy of venetoclax (VEN) with vincristine (VCR). We designed a phase I/II trial (EA9152) of the combination of L-VCR and VEN for patients with r/r B-or T-cell ALL or LL. Here, we report the safety and efficacy outcomes of the phase I portion of this trial (NCT03504644).
Methods
In a 3+3 dose escalation design, r/r ALL subjects were given single-agent VEN doses reaching 400, 600, or 800 mg for the three respective dose levels. Weekly L-VCR at 2.25 mg/m2 IV was started on D15 of cycle 1. The primary phase I objective was to determine the maximum tolerated dose (MTD) of the combination.
Results
Among the 18 patients in phase I, grade ≥ 3 treatment-related adverse events were reported in 89% of treated patients. Two patients (two of three) at dose level 3 experienced dose-limiting toxicities. Therefore, the MTD of the combination was determined to be dose level 2 (VEN 600 mg). Twenty-two percent of evaluable patients (N = 4) achieved a complete response, with two of them showing no evidence of measurable residual disease (MRD).
Conclusion
The combination of VEN and L-VCR was found to be safe for patients with r/r ALL and encouraging preliminary efficacy, including MRD negative responses. With the removal of L-VCR from the US market, the phase 2 portion of this trial is actively enrolling with vincristine sulfate.