Phase I/II of Venetoclax in Combination With Azacitidine in Treatment Naïve and Relapse Refractory High Risk MDS Individuals"
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Incidence of adverse events (Phase I)
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of venetoclax when given together with azacitidine in treating patients with high-risk myelodysplastic syndrome that has come back (recurrent) or does not respond to treatment (refractory). Drugs used in chemotherapy, such as venetoclax and azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
详细描述
PRIMARY OBJECTIVE:
I. To determine the safety and tolerability (phase 1) and overall response rate (ORR) (phase 2) of venetoclax in combination with azacitidine in patients with treatment-naive high-risk myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) with bone marrow excess blasts > 5% and patients that are relapsed/refractory to prior hypomethylating agent (HMA) therapy.
SECONDARY OBJECTIVES:
I. Rate of complete remission (CR). II. Rate of marrow/morphologic complete remission (mCR). III. Rate of hematologic improvement (HI; erythroid/platelet/neutrophil responses).
IV. Rate of red blood cell (RBC) transfusion independence. V. Rate of platelet (PLT) transfusion independence. VI. Rate of cytogenetic response. VII. Rate of bone marrow blast response. VIII. Time to transformation to acute myeloid leukemia (AML). IX. Duration of response (DOR). X. Overall survival (OS). XI. Progression-free survival (PFS). XII. Time to next MDS treatment (TTNT). XIII. Event-free survival (EFS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •For phase I, patients can be HMA-naive high-risk MDS (Int-2 or high risk by the International Prognostic Scoring System [IPSS] with overall score >= 1.5) with excess blasts > 5%, or relapsed/refractory MDS post-HMA failure (defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy) with > 5% blasts
- •For phase II, patients will be divided into 2 cohorts: Cohort A: patients with HMA-naive high-risk MDS (Int-2 or high risk by the IPSS with overall score >= 1.5) with excess blasts > 5%. Cohort B: patients with relapsed/refractory MDS post-HMA failure (defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy) with > 5% blasts are eligible. Note: Patients with chronic myelomonocytic leukemia (CMML) and therapy-related MDS are eligible. Hydroxyurea is allowed to lower the white cell count =< 10,000/ul prior to initiation of venetoclax
- •Total bilirubin < 3 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
- •Alanine aminotransferase (ALT) < 4 x ULN unless considered due to leukemic involvement
- •Creatinine < 2 x ULN unless related to the disease
- •Signed written informed consent. Consent may be translated for Non-English Speaking Patients per institutional policy.
- •Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment. Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment
- •Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment
排除标准
- •Patients having received any prior BCL2 inhibitor therapy
- •Patients with MDS with IPSS risk categories low or Int-1 (overall IPSS score < 1.5)
- •Pregnant or breastfeeding
- •Cognitively impaired patients
研究组 & 干预措施
Treatment (venetoclax, azacitidine)
Patients receive venetoclax orally PO QD on days 1-7 or 1-14 and azacitidine SC or IV over 15 minutes on days 1-5. Cycles repeat every 4-8 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Azacitidine (Drug)
Treatment (venetoclax, azacitidine)
Patients receive venetoclax orally PO QD on days 1-7 or 1-14 and azacitidine SC or IV over 15 minutes on days 1-5. Cycles repeat every 4-8 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Incidence of adverse events (Phase I)
时间窗: Up to 5 years
Safety data will be summarized by category, severity, and frequency.
Maximum tolerated dose (MTD) of the combination regimen of venetoclax and azacitidine (Phase I)
时间窗: Up to 8 weeks
The MTD is the highest dose level in which \< 2 patients of 6 develop first cycle dose-limiting toxicity.
次要结局
- Rate of marrow/morphologic CR(Up to 5 years)
- Rate of red blood cell transfusion independence(Up to 5 years)
- Rate of cytogenetic response(Up to 5 years)
- Rate of bone marrow blast response(Up to 5 years)
- Time to transformation to acute myeloid leukemia(Up to 5 years)
- Progression-free survival(From treatment to progression or last follow-up, assessed up to 5 years)
- Time to next myelodysplastic syndrome treatment(Up to 5 years)
- Event-free survival(From the date of treatment initiation to the date of documented treatment failure, relapses from CR, or death from any cause, whichever occurs first, assessed up to 5 years)
- Overall response rate (Phase 2)(Up to 5 years)
- Rate of hematologic improvement(Up to 5 years)
- Duration of response(From the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, whichever occurs first, assessed up to 5 years)
- Rate of CR(Up to 5 years)
- Overall survival(From treatment start till death or last follow-up, assessed up to 5 years)
- Rate of platelet transfusion independence(Up to 5 years)