NCT05391750进行中（未招募）1 期
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
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
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.
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
- •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
- •Subjects with a history of autologous transplantation must have adequate peripheral blood counts as defined below, have recovered from any transplant related toxicity(s) and be > 100 days post-autologous transplant (prior to first dose of study drug)
- •Subjects must meet the following laboratory parameters, per laboratory reference range, at least once during the screening period:
- •Absolute neutrophil count (ANC) >= 1000/uL (Subject may use granulocyte colony-stimulating factor [G-CSF] to achieve ANC eligibility criteria)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x upper limit of normal range (ULN)
- •Calculated creatinine clearance >= 30 mL/min using a modified Cockcroft- Gault calculation or a 24-hour urine collection for creatinine clearance
- •Platelet count >= 75,000 cells/mm3 and independent of transfusion for 2 weeks
- •Hemoglobin >= 8.0 g/dL, subjects may not receive blood transfusion within 1 week to achieve hemoglobin eligibility criteria per investigator discretion
- •Total bilirubin =< 1.5 x ULN; subjects with Gilbert's syndrome may have bilirubin > 1.5 x ULN
- •If female, subject must be:
- •Postmenopausal defined as:
- •Age > 55 years with no menses for 24 or more months without an alternative medical cause
- •Age =< 55 years with no menses for 24 or more months without an alternative medical cause
- •AND an follicle stimulating hormone (FSH) level > 40 IU/L. OR
- •Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy) OR
- •A woman of childbearing potential (WOCP) practicing at least one protocol specified method of birth control starting at cycle 1 day 1 (or earlier) through at least 30 days after last dose of study drug
- •Females of childbearing potential (must have negative results for pregnancy test performed:
- •At screening, on a serum or urine sample obtained within 28 days prior to the first study drug administration,
- •Prior to dosing, on a urine sample obtained on the first day of study drug dosing, if it has been > 7 days since obtaining the serum pregnancy test results
- •Females of non-childbearing potential (either postmenopausal or permanently surgically sterile as defined above) at screening do not require pregnancy testing
- •Must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures
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
- •Known human immunodeficiency viral (HIV) infection
- •Active hepatitis B or C infection based on screening blood testing
- •Subject is receiving other ongoing anti-myeloma therapy
- •Subject has received any of the following within 7 days prior to the first dose of study drug:
- •Strong or moderate CYP3A inhibitors, or
- •Strong or moderate CYP3A inducers
- •Subject has received any of the following within 14 days prior to the first dose of study drug or has not recovered to less than a grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy: any anti-myeloma therapy including chemotherapy, radiotherapy, or investigational therapy, including targeted small molecule agents
- •Subject has received prior treatment with a BCL-2 family inhibitor
- •Subject is pregnant, parturient, or breastfeeding; deprived of freedom by judicial or administrative decision; hospitalized and unable to provide consent, or otherwise unable to provide consent
- •Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or star fruit within 3 days prior to the first dose of study drug
- •Subject has received immunization with live vaccine within 60 days of dosing
- •Recent corticosteroid therapy at a cumulative dose equivalent to > 140 mg of prednisone or a single dose equivalent to >= 40 mg of dexamethasone within 2 weeks prior to the first dose of study drug
- •Subject's decision to not divulge the race
研究组 & 干预措施
Treatment (venetoclax, tocilizumab)
Experimental
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 (Biological)
Treatment (venetoclax, tocilizumab)
Experimental
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 (Drug)
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)
研究者
Jonathan Kaufman
Principal Investigator
Emory University
研究点 (1)
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