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Pomalidomide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

2020年4月7日 更新者:Mayo Clinic

MC1082: A Phase I/II Trial of Pomalidomide (CC-4047), Bortezomib, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

RATIONALE: Pomalidomide and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pomalidomide and bortezomib together with dexamethasone may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib when given together with pomalidomide and dexamethasone and to see how well it works in treating patients with relapsed or refractory multiple myeloma.

研究概览

详细说明

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of bortezomib in combination with pomalidomide and dexamethasone.

II. To evaluate the hematologic response rate (PR, VGPR, or CR) of pomalidomide, bortezomib and dexamethasone in patients with relapsed or refractory myeloma.

SECONDARY OBJECTIVES:

I. Time to progression.

II. To assess the toxicity of pomalidomide, bortezomib and dexamethasone in this patient population.

OUTLINE : This is a phase I, dose-escalation study of bortezomib followed by a phase II study. Patients receive oral pomalidomide on days 1-21; bortezomib IV on days 1, 8,15, 22; and oral dexamethasone on days 1, 8, 15, 22 . Treatment repeats every 28 days for 8 courses. Patients then receive maintenance therapy comprising oral pomalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months.

研究类型

介入性

注册 (实际的)

50

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • Arizona
      • Scottsdale、Arizona、美国
        • Mayo Clinic in Arizona
    • Florida
      • Jacksonville、Florida、美国
        • Mayo Clinic in Florida
    • Minnesota
      • Rochester、Minnesota、美国、55905
        • Mayo Clinic

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Serum Creatinine =< 3 mg/dL
  • Absolute neutrophil count >= 1000/uL
  • Platelet count >= 75,000/uL
  • Measurable disease of multiple myeloma as defined by at least ONE of the following:

    • serum monoclonal protein >= 1.0 g/dL
    • > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
    • serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
    • monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
    • measurable plasmacytoma that has not been radiated
  • ECOG Performance status (PS) 0, 1, or 2
  • Previously treated relapsed or refractory multiple myeloma
  • Patients must have received at least one prior therapy but no more than 4 therapies.

    • one or more of the prior regimens must have included lenalidomide and it has been determined the patient is refractory, resistant, or relapsed this therapy
    • prior bortezomib not required but if prior exposure, patients should not be refractory (Refractory means progression on therapy or within 60 days from the last dose of bortezomib.)
  • Provide informed written consent
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide; FCBP must also agree to ongoing pregnancy testing
  • Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy
  • All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • Willing and able to take aspirin or alternate prophylactic anticoagulation
  • All previous cancer therapy, including chemotherapy, high dose corticosteroids, immune modulatory drugs or proteosome inhibitors must have been discontinued >= 2 weeks prior to study registration
  • Any prior treatment with investigational agents must be discontinued >= 28 days prior to study registration
  • Willing to abstain from donating blood during study participation and for 28 days after discontinuation of study drug
  • Men must agree to abstain from donating semen or sperm during study participation and for 28 days after discontinuation of study drug
  • Willingness to return to enrolling institution for follow-up

Exclusion Criteria:

  • Concomitant high dose corticosteroids (concurrent use of corticosteroids); EXCEPTION: Patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, i.e., adrenal insufficiency, rheumatoid arthritis, etc
  • Another malignancy undergoing active treatment with the exception of non melanoma skin cancer or in situ cervical or breast cancer
  • Pregnant women or women of reproductive ability who are unwilling to use effective contraception
  • Nursing women
  • Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment
  • Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
  • Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational: NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
  • Active DVT or PE that has not been therapeutically anticoagulated
  • Known positive for HIV or active hepatitis infection
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Known hypersensitivity to thalidomide or lenalidomide including development of erythema nodosum if characterized by a desquamating rash
  • > grade 2 peripheral neuropathy
  • Any prior use of pomalidomide

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:不适用
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:Arm I
Patients receive oral pomalidomide on days 1-21; bortezomib IV on days 1, 8, 15, 22; and oral dexamethasone on days 1, 8, 15, 22. Treatment repeats every 28 days for 8 courses. Patients then receive maintenance therapy comprising oral pomalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
口头给予
其他名称:
  • Aeroseb-Dex
  • 十年级
  • 十进制
  • 私信
  • 数字XM
  • 脱钙喷雾
可选的相关研究
鉴于IV
其他名称:
  • MLN341
  • PS-341
  • 自民党 341
  • 万卡得
口头给予
其他名称:
  • CC-4047
Optional correlative studies

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Find Maximum Tolerated Dose (MTD) of Bortezomib in Combination With Pomalidomide and Dexamethasone Out to 2.5 Years, by Count of Patients With Dose Limiting Toxicities.
大体时间:2.5 years
MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).
2.5 years
Number of Participants With a Hematologic Response (PR, VGPR, or CR)
大体时间:2.5 years
The number of participants who achieve PR, VGPR, or CR as defined by The International Myeloma Working Group uniform response criteria(2011). sCR: CR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h. PR: > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h. MR: NA. SD: Not meeting criteria for CR, VGPR, PR, or progressive disease. PD: Increase of > 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL), Urine M-component and/or (the absolute increase must be > 200 mg/24 h)
2.5 years

次要结果测量

结果测量
措施说明
大体时间
Progression Free Survival
大体时间:2.5 years
The progression-free survival (PFS) time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. PD: Increase of > 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL), Urine M-component and/or (the absolute increase must be > 200 mg/24 h)
2.5 years
Number of Participants With Adverse Events
大体时间:2.5 years
Reported in Adverse Events section of the results
2.5 years

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

调查人员

  • 学习椅:Martha Lacy, M.D.、Mayo Clinic
  • 首席研究员:Joseph R. Mikhael, M.D.、Mayo Clinic

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2011年9月1日

初级完成 (实际的)

2017年8月15日

研究完成 (实际的)

2018年3月22日

研究注册日期

首次提交

2010年9月29日

首先提交符合 QC 标准的

2010年9月29日

首次发布 (估计)

2010年10月1日

研究记录更新

最后更新发布 (实际的)

2020年4月17日

上次提交的符合 QC 标准的更新

2020年4月7日

最后验证

2019年2月1日

更多信息

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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