Phase I/II Trial of Systemic Administration of Edmonston Strain of Measles Virus, Genetically Engineered to Express NIS, With or Without Cyclophosphamide, in Patients With Recurrent or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I)
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of vaccine therapy when given with or without cyclophosphamide and to see how well they work in treating patients with multiple myeloma that has come back (recurrent) or has not responded to previous treatment (refractory). Vaccines made from a gene-modified virus may help the body build an effective immune response to kill cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, 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. Giving vaccine therapy together with cyclophosphamide may be a better treatment for multiple myeloma.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) when administered with or without cyclophosphamide in patients with relapsed or refractory multiple myeloma. (Phase I) II. To evaluate the confirmed response rate of MV-NIS alone in patients with relapsed or refractory multiple myeloma who have exhausted all therapeutic options. (Phase II, Cohort A) III. To evaluate the confirmed response rate of MV-NIS alone in patients who are relapsing from very good partial response (VGPR) or complete response (CR) and have not received myeloma directed therapy for at least 12 weeks. (Phase II, Cohort B)
SECONDARY OBJECTIVES:
I. To determine the safety and toxicity of the intravenous administration of an Edmonston vaccine strain measles virus engineered to express the thyroidal sodium iodide symporter (MV-NIS) when administered with or without cyclophosphamide in patients with relapsed or refractory multiple myeloma. (Phase I) II. To evaluate the confirmed response rate of MV-NIS in patients with relapsed or refractory multiple myeloma. (Phase I) III. To further evaluate the adverse event profile of MV-NIS in patients with relapsed or refractory multiple myeloma. (Phase II) IV. To evaluate overall survival, failure-free survival and progression-free survival. (Phase II)
TERTIARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Myeloma relapsing from partial response or better
- •Patients relapsing > 18 months from transplant if not on maintenance, or
- •If off maintenance, discontinued at least 6 months ago, or
- •If relapsing on maintenance, at least 3 years from transplant, or
- •Off prior myeloma therapy at least 6 months ago
- •Sufficient tumor burden that is assessable for response
- •Serum M-spike >= 0.5 g/dL, or
- •If immunoglobulin A (IgA) myeloma, IgA > 1000 mg/dL, or
- •Difference between involved and uninvolved free light chain (dFLC) > 10 mg/dL, or
- •Urine M-spike >= 200 mg/24 hours, or
- •Bone marrow plasmacytosis >= 10%, or
- •Plasmacytoma >= 2 cm in diameter
- •Absolute neutrophil count (ANC) >= 1000/uL
- •Platelets (PLT) >= 50,000/uL
- •Hemoglobin >= 8.5 g/dl
- •Aspartate aminotransferase (AST) =< 2 times upper limit of normal
- •Creatinine < 2 times upper limit of normal
- •Total bilirubin =< 1.5 x upper limit of normal
- •International normalized ratio (INR) =< 1.4 x ULN at the time of registration
- •Ability to provide informed consent
- •Willingness to return to Mayo Clinic Rochester for follow-up
- •Life expectancy >= 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- •Willingness to provide all biological specimens as required by the protocol
- •Negative serum pregnancy test done =< 7 days prior to registration for women of childbearing potential only
- •Measles antibody titer on the BioRad Multiplex assay less than or equal to 1.0
排除标准
- •Uncontrolled infection
- •Active tuberculosis
- •Any myeloma directed therapy within 12 weeks of registration including plasmapheresis or transfusion
- •New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review
- •Active central nervous system (CNS) disorder or seizure disorder
- •Human immunodeficiency virus (HIV) positive test result
- •Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (used for a non-Food and Drug Administration [FDA] approved indication and in the context of a research investigation)
- •Previous exposure to heat inactivated measles virus vaccine (this vaccine was given to some individuals between the years of 1963-1967)
- •Any of the following:
- •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
- •Evidence of chronic or acute graft versus host disease or on-going treatment for graft versus host disease from prior allogeneic stem cell transplantation
- •Exposure to household contacts =< 15 months old or household contact with known immunodeficiency
研究组 & 干预措施
Stage 1 (MV-NIS alone)
Patients receive MV-NIS IV over 1 hour on day 1. (Closed to accrual on 12/17/2009 and reopened 10/13/2011)
干预措施: Laboratory Biomarker Analysis (Other)
Stage 1 (MV-NIS alone)
Patients receive MV-NIS IV over 1 hour on day 1. (Closed to accrual on 12/17/2009 and reopened 10/13/2011)
干预措施: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter (Biological)
Stage 1 (MV-NIS alone)
Patients receive MV-NIS IV over 1 hour on day 1. (Closed to accrual on 12/17/2009 and reopened 10/13/2011)
干预措施: Pharmacological Study (Other)
Stage 2 (MV-NIS and cyclophosphamide)
Patients receive cyclophosphamide IV over 30 minutes and then MV-NIS IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11)
干预措施: Cyclophosphamide (Drug)
Stage 2 (MV-NIS and cyclophosphamide)
Patients receive cyclophosphamide IV over 30 minutes and then MV-NIS IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11)
干预措施: Laboratory Biomarker Analysis (Other)
Stage 2 (MV-NIS and cyclophosphamide)
Patients receive cyclophosphamide IV over 30 minutes and then MV-NIS IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11)
干预措施: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter (Biological)
Stage 2 (MV-NIS and cyclophosphamide)
Patients receive cyclophosphamide IV over 30 minutes and then MV-NIS IV over 1 hour 2 days later. (Temporarily closed to accrual on 10/13/11)
干预措施: Pharmacological Study (Other)
结局指标
主要结局
Number of Phase I Participants With Dose-Limiting Toxicity Events (Phase I)
时间窗: 6 weeks
The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include non-hematologic events graded 3 or higher and deemed at least possibly related to treatment. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. The number of patients reporting a dose-limiting event are reported.
Maximum Tolerated Dose (MTD) (Phase I)
时间窗: 6 weeks
The Maximum Tolerated Dose (MTD) is defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Dose-limiting toxicities include non-hematologic events graded 3 or higher and deemed at least possibly related to treatment. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. The MTD is reported below.
Proportion of Confirmed Response, Defined as a Partial Response (PR) or Better (Phase II)
时间窗: Up to 1 year
Confirmed response will be evaluated using all cycles. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
次要结局
- Overall Survival (Phase II)(Time from registration to death due to any cause, assessed up to 1 year)
- Failure-free Survival (Phase II)(Time from registration to the earliest of progressive disease, alternative treatment for myeloma, or death due to any cause, assessed up to 1 year)
- Overall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase I)(Up to 1 year)
- Overall Toxicity Rate, Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0) (Phase II)(Up to 1 year)
- Number of Patients With Clinical Responses (Phase I)(Up to 1 year)
- Progression-free Survival (Phase II)(Up to 5 years)
- Time to Progression (TTP) (Phase II)(Time from registration to the earliest date with documentation of disease progression, assessed up to 1 year)