2024-520121-36-00招募中2 期
STEP-WISE COMBINATION OF OBINUTUZUMAB, VEMURAFENIB AND COBIMETINIB IN PATIENTS WITH HAIRY CELL LEUKEMIA (HCL) PREVIOUSLY TREATED WITH PURINE ANALOGS OR UNFIT FOR CHEMOTHERAPY: A PHASE-2, SINGLE-ARMS, ITALIAN, MULTICENTER STUDY (HCL-PG04)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 8
- 主要终点
- 1. The primary endpoint in each cohort is to meet or exceed a pre-determined rate of response (complete or overall response as specified later for each cohort) according to a per-protocol analysis. The rate of response will be also calculated according to the intention-to-treat analysis for informative purpose only, because this is a phase- 2 non-randomized trial primarily designed to test the anti-leukemic activity of the study drugs.
研究概览
简要总结
To determine the depth of anti-leukemic activity of the study drugs vemurafenib, cobimetinib and obinutuzumab in three distinct cohorts of eligible HCL patients carrying the BRAF-V600E mutation and receiving the study drugs in step-wise combinations (Cohort-1/Phase-A, Cohort-1/Phase-B, Cohort-2 and Cohort-3).
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Male or female HCL patients ≥ 18 years of age.
- •Signed informed consent must be obtained prior to performing any study-related procedures.
- •Clinical indication for treatment, i.e. the presence of one or more of the following: neutrophils <1.5x109 per liter, hemoglobin <11 g per deciliter, platelets <100x109 per liter, bulky and/or symptomatic splenomegaly, clinically relevant infiltration of other organs (e.g., lymphadenopathy), recurrent disease-related opportunistic infections.
- •Proven diagnosis of HCL according to the morphological and immunophenotypic criteria (co-expression of CD11c/CD25/CD103 and/or positivity for annexin-A1) of the World Health Organization (WHO-2008) classification of lymphoid neoplasms12, accompanied by the presence of the BRAF-V600E mutation as detected using a sensitive allele-specific polymerase chain reaction (AS-PCR) recently developed in our laboratory
- •Patients with HCL must fall in one of the categories indicated in the “Overview” of study population.
- •Any prior treatment (chemotherapy and/or immunotherapy) must have been completed at least 12 weeks prior to initiation of study medication, except if no response to this treatment is already manifestly evident earlier.
- •ECOG performace status 0-
- •Patients must have recovered from all side effects of their most recent treatment for HCL.
- •Negative serum pregnancy test within 14 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year.
- •Fertile men and women must use an effective method of contraception during treatment and for at least 16 weeks (for men) and 12 months (for women) after completion of treatment as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly (for example implants, injectables, or intrauterine devices). Oral contraceptives are not reliable due to potential drug-drug interaction. At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
- •Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry.
排除标准
- •Concurrent administration of any anti-cancer therapies (e.g. chemotherapy, other targeted therapy, experimental drug, etc.) other than those administered in this study and concurrent treatment on another therapeutic clinical trial.
- •Inability to comply with other requirements of the protocol
- •Pregnant (negative serum pregnancy test is required in women of child-bearing potential) or lactating women.
- •Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption. Patients must be able to swallow tablets.
- •History of congenital long QT syndrome
- •Corrected QT (QTc) interval ≥500 msec at baseline or uncorrectable electrolyte abnormalities.
- •Active hepatitis infection.
- •Uncontrolled medical illness.
- •Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, or which in the judgment of the investigator would make the patient inappropriate for entry into this study.
- •Unwillingness to practice effective birth control.
结局指标
主要结局
1. The primary endpoint in each cohort is to meet or exceed a pre-determined rate of response (complete or overall response as specified later for each cohort) according to a per-protocol analysis. The rate of response will be also calculated according to the intention-to-treat analysis for informative purpose only, because this is a phase- 2 non-randomized trial primarily designed to test the anti-leukemic activity of the study drugs.
1. The primary endpoint in each cohort is to meet or exceed a pre-determined rate of response (complete or overall response as specified later for each cohort) according to a per-protocol analysis. The rate of response will be also calculated according to the intention-to-treat analysis for informative purpose only, because this is a phase- 2 non-randomized trial primarily designed to test the anti-leukemic activity of the study drugs.
次要结局
- 1. To describe the type, incidence, grade and relationship to the study drugs of adverse events (AE) occurring in each cohort.
- 2. To describe separately in each cohort: the time to response; the relapse-free survival (or response duration); the treatment-free survival; the progression-free survival; the event-free survival; the disease-specific survival; the overall survival; the specific type of, and response to, other anti-leukemic treatments.
研究者
Enrico Tiacci
Scientific
Universita' Degli Studi Di Perugia
研究点 (8)
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