A Phase 1 Study Evaluating the Safety of Venetoclax and Tocilizumab in African American and Non-African American Subjects With Relapsed or Refractory t(11;14) Multiple Myeloma
概览
- 阶段
- 1 期
- 干预措施
- Tocilizumab
- 疾病 / 适应症
- Recurrent Plasma Cell Myeloma
- 发起方
- Emory University
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD)
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
This phase I trial finds out the best dose and side effects of venetoclax and tocilizumab in treating patients with t(11;14) multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Tocilizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Tocilizumab is used to treat side effects from immune therapy in patients with myeloma. Giving venetoclax and tocilizumab may kill more cancer cells.
详细描述
PRIMARY OBJECTIVE: I. To determine the dose limiting toxicity (DLT), safety profile, and the recommended phase 2 dose (RPTD) of venetoclax and tocilizumab when administered in subjects with relapsed and recurrent (RR) multiple myeloma t(11;14) (MM). SECONDARY OBJECTIVES: I.To evaluate the preliminary efficacy data regarding the effect of venetoclax and tocilizumab by objective response rate per IMWG criteria. II. To evaluate the effect of chronic tocilizumab administration on venetoclax exposure. TERTIARY/EXPLORATORY OBJECTIVES: I. To evaluate the preliminary efficacy data regarding the effect of venetoclax and tocilizumab by time to response (TTR), time to disease progression (TTP), duration of response (DOR), progression free survival (PFS) and overall survival (OS). II. To measure the effect of IL6 receptor blockade on ex vivo venetoclax sensitivity. III. To evaluate the cell populations in the bone marrow of responders versus non-responders as well as the effect of IL6 receptor blockade on those populations. IV. To evaluate the expression of B cell markers on venetoclax sensitive myeloma. V. To determine the expression of key BCL2 family members with and without IL6 receptor blockade. VI. To correlate differences in somatic mutations, structural alterations, gene expression and chromatin accessibility with venetoclax response. OUTLINE: This is a dose-escalation study of venetoclax and tocilizumab. Patients receive tocilizumab intravenously (IV) on day -7 of cycle 1, and on day 1 of subsequent cycles. Patients also receive venetoclax orally (PO) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks, then every 6 months thereafter.
研究者
Jonathan Kaufman
Principal Investigator
Emory University
入排标准
入选标准
- •Subject must be \>= 18 years of age Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of =\< 2
- •Diagnosis of multiple myeloma that requires treatment and has been previously treated with:
- •Has received at least 2 prior lines of therapy
- •Has had documented disease progression on or within 60 days after completion of the last therapy.
- •Has received at least 2 consecutive cycles of lenalidomide and be relapsed/refractory to lenalidomide, as defined per protocol.
- •Has received at least 2 consecutive cycles of a proteasome inhibitor (PI). Have MM positive for t(11;14) translocation as determined by an analytically validated fluorescence in-situ hybridization (FISH) assay per the central laboratory testing
- •Subject must have had measurable disease at Screening, defined as any of the following:
- •Serum monoclonal protein \>= 1.0 g/dL (\>= 10 g/L) by protein electrophoresis, or
- •\>= 200 mg of monoclonal protein in the urine on 24-hour electrophoresis, or
- •Serum immunoglobulin free light chain (FLC) \>= 10 mg/dL provided serum FLC ratio is abnormal
排除标准
- •Subject exhibits evidence of other clinically significant uncontrolled condition(s), including, but not limited to:
- •Acute infection within 14 days prior to first dose of study drug requiring antibiotic, antifungal, or antiviral therapy
- •Diagnosis of fever and neutropenia within 1 week prior to first dose of study drug
- •Subject has a cardiovascular disability status of New York Heart Association class \>= 3
- •Subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular or hepatic disease within the last 6 months that, in the opinion of the investigator, would adversely affect his/her participation in the study
- •Subject has a history of other active malignancies other than multiple myeloma within the past 3 years prior to study entry, with the following exceptions:
- •Adequately treated in situ carcinoma of the cervix uteri,
- •Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin,
- •Localized prostate cancer Gleason grade 6 or lower AND with stable prostate specific antigen (PSA) levels off treatment
- •Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent
研究组 & 干预措施
Treatment (venetoclax, tocilizumab)
Patients receive tocilizumab IV on day -7 of cycle 1, and on day 1 of subsequent cycles. Patients also receive venetoclax PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Tocilizumab
Treatment (venetoclax, tocilizumab)
Patients receive tocilizumab IV on day -7 of cycle 1, and on day 1 of subsequent cycles. Patients also receive venetoclax PO on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Venetoclax
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: Completion of cycle 1 (each cycle is 21 days)
The MTD for each arm is selected based on isotonic regression27, using the shiny app BOINComb (http://www.trialdesign.org). The dose is selected as the MTD for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate. If there are ties, the higher dose level is selected when the isotonic estimate is lower than the target toxicity rate; the lower dose level is selected when the isotonic estimate is greater than or equal to the target toxicity rate.
次要结局
- Overall response rate (ORR)(Up to 5 years)
- Incidence of adverse events (AEs)(Up to 30 days post-treatment)
- Complete response rate(Up to 5 years)
- Duration of response (DOR)(From date of treatment response to date of disease progression, assessed up to 5 years)
- Progression-free survival (PFS)(From date of receipt of study treatment to date of disease progression or death from any cause, where those alive without are censored at date of last follow-up, assessed up to 5 years)
- Time to response (TTR)(From date of receipt of study treatment to date of treatment response, where those not responding are censored at date of last follow-up or death from any cause, assessed up to 5 years)
- Overall survival (OS)(From date of receipt of study treatment to date of death from any cause, where those alive without are censored at date of last follow-up, assessed up to 5 years)
- Time to disease progression (TTP)(From date of receipt of study treatment to date of disease progression, where those not progressing or have died are censored at date of last follow-up or death from any cause, assessed up to 5 years)