Phase 2 Trial of Pomalidomide, Ixazomib and Dexamethasone in Patients With Multiple Myeloma With Extramedullary Disease or Plasma Cell Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- Confirmed Response Rate
研究概览
简要总结
This phase II trial studies how well pomalidomide, ixazomib citrate, and dexamethasone work in treating patients with previously treated multiple myeloma or plasma cell leukemia. Biological therapies, such as pomalidomide and dexamethasone, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving pomalidomide, ixazomib citrate, and dexamethasone together may be more effective in treating multiple myeloma.
详细描述
PRIMARY OBJECTIVES:
I. To determine the confirmed response rate (>= partial response [PR]) of ixazomib citrate (ixazomib), used in combination with pomalidomide and dexamethasone in patients with previously treated multiple myeloma (MM) with extramedullary disease.
SECONDARY OBJECTIVES:
I. To determine the toxicities associated with ixazomib in combination with pomalidomide and dexamethasone in patients with previously treated MM with extramedullary disease.
II. To determine the differential response rates (biochemical versus extramedullary disease) with ixazomib in combination with pomalidomide and dexamethasone in patients with previously treated MM with extramedullary disease.
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
- •Previously treated myeloma, currently with extramedullary disease (defined as plasmacytoma outside bone marrow that is not contiguous with a bone lesion) with at least one lesion that has a single diameter of >= 2 cm or plasma cell leukemia (defined as circulating plasma cells exceeding 5% of peripheral blood leukocytes or 0.5 X 10^9/L or 200 cells/150000 events by flow cytometry)
- •Calculated creatinine clearance (using Cockcroft-Gault equation) >= 30 mL/min
- •Absolute neutrophil count (ANC) >= 1000/mm^3
- •Platelet count >= 50,000/mm^3
- •Hemoglobin >= 8.0 g/dL
- •Patients with measurable disease defined as at least one of the following:
- •For patients with extramedullary disease (EMD) measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) or the CT portion of the positron emission tomography (PET)/CT: must have at least one lesion that has a single diameter of >= 2 cm; skin lesions can be used if the area is >= 2 cm in at least one diameter and measured with a ruler
- •Plasma cell count >= 0.5 X 10^9/L or 5 percent of the peripheral blood white cells
- •Plasma cell count if determined by flow cytometry, >= 200/150,000 events
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- •Provide informed written consent
- •Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- •All study participants must be registered into the mandatory pomalidomide (POMALYST) Risk Evaluation and Mitigation Strategy (REMS) program, and be willing and able to comply with the requirements of the POMALYST REMS program
- •Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- •Willing to provide bone marrow and blood samples for correlative research purposes
排除标准
- •Other malignancy requiring active therapy
- •EXCEPTIONS: Non-melanoma skin cancer, ductal breast carcinoma in situ (DCIS) or carcinoma-in-situ of the cervix
- •NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
- •Females of childbearing potential (FCBP)* must have a negative serum pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours prior to prescribing pomalidomide for cycle 1 (prescriptions must be filled within 7 days as required by RevAssist [lenalidomide REMS program]), 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 successful vasectomy; patient must follow pregnancy testing requirements as outlined in the POMALYST REMS program
- •A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •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
- •Patient has >= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
- •Major surgery =< 14 days before study registration
- •Systemic treatment with strong CYP3A4 inducers (e.g. rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, gingko biloba, St. John's wort) within 7 days before registration
- •Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months; Note: prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
- •Corrected QT Interval (QTc) > 470 milliseconds (msec) on a 12-lead ECG obtained during the screening period
- •Note: If a machine reading is above this value, the ECG should be reviewed by a qualified reader and confirmed on a subsequent ECG
- •Known human immunodeficiency virus (HIV) positive
- •Known hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
- •Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
- •Known allergy to any of the study medications, their analogues or excipients in the various formulations
- •Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
- •Diarrhea > grade 1, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading, in the absence of antidiarrheals
研究组 & 干预措施
Treatment (ixazomib citrate, pomalidomide, dexamethasone)
Patients receive ixazomib citrate PO on days 1, 8, and 15, pomalidomide PO on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (ixazomib citrate, pomalidomide, dexamethasone)
Patients receive ixazomib citrate PO on days 1, 8, and 15, pomalidomide PO on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Dexamethasone (Drug)
Treatment (ixazomib citrate, pomalidomide, dexamethasone)
Patients receive ixazomib citrate PO on days 1, 8, and 15, pomalidomide PO on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Ixazomib Citrate (Drug)
Treatment (ixazomib citrate, pomalidomide, dexamethasone)
Patients receive ixazomib citrate PO on days 1, 8, and 15, pomalidomide PO on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pomalidomide (Drug)
结局指标
主要结局
Confirmed Response Rate
时间窗: 4 years
A confirmed response is defined as a patient who has achieved a stringent complete response (sCR), complete response (CR), very good partial response (PR), or PR on two consecutive evaluations. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. 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
- Biochemical Response Rate(4 years)
- Extramedullary Response Rate(4 years)
- Progression-free Survival(4 years 8 months)
- Incidence of Adverse Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0(4 years 1 month)