Solitary Plasmacytoma of Bone: Randomized Phase III Trial to Evaluate Treatment With Adjuvant Systemic Treatment and Zoledronic Acid Versus Zoledronic Acid After Definite Radiation Therapy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 388
- 主要终点
- Symptomatic Myeloma Progression Free-survival (PFS) Rate
研究概览
简要总结
This randomized phase III trial compares ixazomib citrate, lenalidomide, dexamethasone and zoledronic acid with zoledronic acid alone to see how well they work when given after radiation therapy in treating patients with solitary plasmacytoma of bone. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may help the immune system kill abnormal blood cells or cancer cells. Dexamethasone is a drug used in chemotherapy that may cause tumor cells to die. Zoledronic acid may prevent bone fractures and reduce bone pain, and may also improve survival. Standard treatment for this cancer is radiation therapy alone. It is not yet known whether ixazomib citrate, lenalidomide, dexamethasone and zoledronic acid or zoledronic acid alone is more effective, and whether adding these treatments after radiation therapy is more effective than radiation therapy alone in treating patients with solitary plasmacytoma of bone.
详细描述
This phase III randomized clinical trial was designed to assess the impact of the addition of ixazomib, lenalidomide, and dexamethasone to zoledronic acid the multiple myeloma progression rate at 5 years. A dynamic allocation procedure will be used to allocate an equal number of patients to each of the treatment arms. This procedure will balance the number of patients which falls into each of the following categories between the two treatment arms:
- % of abnormal plasma cells in the bone marrow: 5-9%
- age < 60; % of abnormal plasma cells in the bone marrow < 5%; and monoclonal protein/clonal light chains present in the blood or urine
- age < 60; % of abnormal plasma cells in the bone marrow < 5% and no monoclonal protein/clonal light chains present in the blood or urine, (MRD+) minimal residual disease
- age ≥ 60; % of abnormal plasma cells in the bone marrow < 5%; and monoclonal protein/clonal light chains present in the blood or urine
- age ≥ 60; % of abnormal plasma cells in the bone marrow < 5% and no monoclonal protein/clonal light chains present in the blood or urine, (MRD+) minimal residual disease
The primary and secondary objectives are described below.
Primary objective
To assess whether ixazomib, lenalidomide, dexamethasone with zoledronic acid is more promising than zoledronic acid alone in increasing the time before progression to multiple myeloma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Pre-registration eligibility criteria (Step 0)
- •Documentation of Disease: Histologic Documentation of Solitary Bone Plasmacytoma
- •For patients pre-registering after the completion of radiation therapy, documentation of a bone marrow aspirate and biopsy containing <10% clonal plasma cells done at most 28 days prior to start of radiation therapy
- •For patients pre-registering before the start of radiation therapy, radiation therapy scheduled to begin at most 28 days after a bone marrow aspirate and biopsy were performed containing <10% clonal plasma cells
- •Participants must have disease that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains or by minimal residual detection. Measurable disease is defined as one or more of the following:
- •serum M protein > 0.5 G/DL, or
- •urine M protein >200 MG/24H, and/or
- •serum FLC assay: involved FLC level > 10 MG/DL with abnormal serum FLC ratio
- •≥ 50 Plasma cells detectable by multicolor flow cytometry, at a sensitive level of 10^-4
- •Age ≥ 18 years
- •ECOG Performance Status 0-2
- •Registration Eligibility Criteria (Step 1)
- •Documentation of Disease:
- •No lytic lesions on skeletal survey and whole body PET/CT other than a single lesion associated with solitary bone plasmacytoma within 28 days prior to registration.
- •Participants must have disease that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains or by minimal residual detection. Measurable disease is defined as one or more of the following:
- •serum M protein > 0.5 G/DL, or
- •urine M protein >200 MG/24H, and/or
- •serum FLC assay: involved FLC level > 10 MG/DL with abnormal serum FLC ratio
- •≥ 50 Plasma cells detectable by multicolor flow cytometry, at a sensitive level of 10^-4
- •Prior Treatment
- •No major surgery within 21 days of registration with stabilization or resolution of surgical adverse events.
- •No investigational agent within 21 days prior to registration
- •No ongoing therapy with corticosteroids greater than 10 mg of prednisone or its equivalent per day. Please note: Inhaled and topical steroids are permitted.
- •No prior proteasome inhibitor or IMiD use.
- •Prior bisphosphonate use is permitted.
- •For all patients:
- •Radiation dose should range from 4500 cGy to 6000 cGy
- •No treatment for this disease following radiation therapy
- •Registration must be completed within 90 days of completion of radiation therapy.
- •Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown and an agent that has known genotoxic, mutagenic and teratogenic effects.
- •Females of childbearing potential (FCBP), defined as a sexually mature female who 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal for at least 24 consecutive months that is, has not had menses at any time in the preceding 24 consecutive months:
- •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 lenalidomide.
- •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 lenalidomide.
- •must 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.
- •ECOG Performance Status 0-2
- •Required Initial Laboratory Values within 14 days of registration:
- •Absolute Neutrophil Count (ANC) ≥ 1,500/mm^3
- •Platelet Count ≥ 75,000/mm^3
- •Hemoglobin ≥ 10 g/dL
- •Serum Creatinine < 2.0 mg/dL [176.8 µmol/liter]
- •Serum calcium ≤ 11.5 mg/dL
- •Calc. Creatinine Clearance > 50 mL/min
- •Bilirubin ≤ 1.5 x upper limits of normal (ULN)
- •AST ≤ 2.5 x upper limits of normal (ULN)
- •Intercurrent or Recent Illness
- •If history of prior malignancy, subject should be in complete remission for ≥ 5 years at the time of registration (with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection).
- •HIV + patients are eligible provided they meet the other eligibility criteria and:
- •CD4+ cells are ≥ 250/mm^3
- •There is no history of AIDS defining conditions other than historically low CD4+ cell count.
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排除标准
- 未提供
研究组 & 干预措施
ixazomib + lenalidomide + dexamethasone + zoledronic acid
Patients receive 4 mg ixazomib by mouth on days 1, 8 and 15. Patients also receive 15 mg lenalidomide by mouth on days 1-21, 12 mg dexamethasone by mouth on days 1, 8, 15, and 22 and zoledronic acid (dose based on creatinine clearance on day 1) IV infusion on day 1. Patients receive treatment every 28 days for a maximum of 6 cycles.
干预措施: ixazomib (Drug)
ixazomib + lenalidomide + dexamethasone + zoledronic acid
Patients receive 4 mg ixazomib by mouth on days 1, 8 and 15. Patients also receive 15 mg lenalidomide by mouth on days 1-21, 12 mg dexamethasone by mouth on days 1, 8, 15, and 22 and zoledronic acid (dose based on creatinine clearance on day 1) IV infusion on day 1. Patients receive treatment every 28 days for a maximum of 6 cycles.
干预措施: zoledronic acid (Drug)
ixazomib + lenalidomide + dexamethasone + zoledronic acid
Patients receive 4 mg ixazomib by mouth on days 1, 8 and 15. Patients also receive 15 mg lenalidomide by mouth on days 1-21, 12 mg dexamethasone by mouth on days 1, 8, 15, and 22 and zoledronic acid (dose based on creatinine clearance on day 1) IV infusion on day 1. Patients receive treatment every 28 days for a maximum of 6 cycles.
干预措施: dexamethasone (Drug)
ixazomib + lenalidomide + dexamethasone + zoledronic acid
Patients receive 4 mg ixazomib by mouth on days 1, 8 and 15. Patients also receive 15 mg lenalidomide by mouth on days 1-21, 12 mg dexamethasone by mouth on days 1, 8, 15, and 22 and zoledronic acid (dose based on creatinine clearance on day 1) IV infusion on day 1. Patients receive treatment every 28 days for a maximum of 6 cycles.
干预措施: lenalidomide (Drug)
zoledronic acid
Patients receive zoledronic acid (dose based on creatinine clearance on day 1) IV on day 1. Patients receive treatment every 28 days for a maximum of 6 cycles.
干预措施: zoledronic acid (Drug)
结局指标
主要结局
Symptomatic Myeloma Progression Free-survival (PFS) Rate
时间窗: 18 months
Symptomatic myeloma PFS is defined as time from randomization to the first instance of criteria for multiple myeloma (MM). MM is defined as clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following: * Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: Hypercalcaemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than the upper limit of normal or \>2.75 mmol/L (\>11 mg/dL); Renal insufficiency: creatinine clearance \<40 mL per min or serum creatinine \>177 μmol/L (\>2 mg/dL); Anaemia: haemoglobin value of \>20 g/L below the lower limit of normal, or a haemoglobin value \<100 g/L; Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT * Any one or more of the following biomarkers of malignancy: Clonal bone marrow plasma cell percentage ≥60%; Involved:uninvolved serum free light chain ratio ≥100 ; \>1 focal lesions on MRI studies
次要结局
- Changes in Minimal Residual Disease From Study Entry to the Completion of Adjuvant Treatment (Approximately Six Months Post-registration) and at 1 Year Post-registration(at 6 and 12 months post-registration)