A Randomized, Multi-Center, Phase II Study of Vemurafenib Plus Obinutuzumab vs. Cladribine Plus Rituximab in Patients With Previously Untreated Hairy Cell Leukemia (HCL)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 86
- 试验地点
- 18
- 主要终点
- incidences of ≥ grade 3 treatment-related toxicities
研究概览
简要总结
The researchers are doing this study to compare the safety of vemurafenib in combination with obinutuzumab to the standard of approach of cladribine in combination with rituximab. The researchers will look at which treatment causes fewer or milder side effects. Researchers think vemurafenib and obinutuzumab (non-chemotherapy drugs) may cause fewer side effects compared with the usual approach of chemotherapy drugs. They will also compare the two approaches to see which approach is more effective at eliminating cancer cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be ≥ 18 years of age
- •Histologically confirmed classical HCL by the enrolling institution
- •Presence of BRAF V600E mutation as confirmed by PCR, NGS or immunohistochemistry. If patient is known to have negative BRAF mutation, repeat testing is advisable as well as discussion with the main study principal investigator.
- •Has not received any prior therapy for the disease
- •Patients who meet the standard treatment initiation criteria, as defined by ANC ≤1.0, Hgb ≤ 10.0 or PLT ≤100K
- •ECOG performance status of 0 - 2
- •Acceptable pre-study organ function during screening as defined as:
- •Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), except in patients with known Gilbert's syndrome who may be enrolled if direct bilirubin ≤ 3 x ULN);
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x ULN; and
- •Serum creatinine ≤ 1.5x ULN
- •Electrocardiogram (ECG) without evidence of clinically significant ventricular arrhythmias or ischemia as determined by the investigator and a rate-corrected QT interval (QTc, Bazett's formula) of < 480 msec
- •For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of vemurafenib and cladribine, and 18 months after discontinuation of rituximab and obinutuzumab
- •For men with female partners of childbearing potential, agreement to use a latex condom and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of vemurafenib
- •Negative serum pregnancy test within 7 days of commencement of treatment in women of childbearing potential
排除标准
- •Have had previous treatment for HCL, including purine analogs, vemurafenib, rituximab, obinutuzumab, and other investigational agents. Previous treatment with transfusions and other supportive care such as G-CSF and erythropoietin are allowed.
- •Known hypersensitivity to any of the study drugs.
- •Patients with known long QT syndrome or uncorrectable electrolyte abnormalities
- •Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
- •Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibody
- •° Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody [HBcAb] and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly DNA testing and take HBV viral prophylaxis such as entecavir.
- •Known infection with HIV or human T-cell leukemia virus 1 (HTLV-1)
- •Active uncontrolled infection, e.g. persistent bacteremia, supplemental oxygen or pressor supports, etc.
- •Live vaccination within 28 days of randomization
- •Patients with concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation or hormonal therapy, with the exception of squamous and basal cell carcinoma of the skin, in situ cervical cancer, adequately treated stage I/II cancer from which the patient is current in complete remission, or any other cancer from which the patient has been disease free for five years
- •Malabsorption syndrome or other condition that precludes enteral route of administration
- •Patients with HCL variant (as defined by absence of expression of CD25)
- •Pregnant or lactating, or intending to become pregnant during the study
研究组 & 干预措施
Vemurafenib plus Obinutuzumab
Patients assigned to the study arm will receive vemurafenib orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days) for a total of 4 cycles. Obinutuzumab will be administered concomitantly with vemurafenib starting at cycle 2 of treatment in cycles of 4 weeks. Obinutuzumab infusions will be administered on days 1, 8 and 15 during the cycle 2 and every 4 weeks during the cycle 3 and 4 of treatment.
干预措施: Vemurafenib (Drug)
Vemurafenib plus Obinutuzumab
Patients assigned to the study arm will receive vemurafenib orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days) for a total of 4 cycles. Obinutuzumab will be administered concomitantly with vemurafenib starting at cycle 2 of treatment in cycles of 4 weeks. Obinutuzumab infusions will be administered on days 1, 8 and 15 during the cycle 2 and every 4 weeks during the cycle 3 and 4 of treatment.
干预措施: Obinutuzumab (Drug)
Standard treatment of Cladribine plus Rituximab
Patients assigned to the SOC arm will receive cladribine IV on days 1-5 concurrently with rituximab IV per week for 8 times, i.e., weekly x8 from day 1.
干预措施: Rituximab (Drug)
Standard treatment of Cladribine plus Rituximab
Patients assigned to the SOC arm will receive cladribine IV on days 1-5 concurrently with rituximab IV per week for 8 times, i.e., weekly x8 from day 1.
干预措施: Cladribine (Drug)
结局指标
主要结局
incidences of ≥ grade 3 treatment-related toxicities
时间窗: within 6 months of treatment
per CTCAE v5.0 within first 6 months from the start of the treatment to account delayed toxicities of the treatments
次要结局
- complete remission(2 years)
- partial response(2 years)