Phase II Subcutaneous VELCADE and Oral Cyclophosphamide-based Induction + Sequential VELCADE and Revlimid Maintenance for Newly Diagnosed Multiple Myeloma in Non-transplant Candidates: An Entirely Non-intravenous Regimen
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR) During Induction Therapy
研究概览
简要总结
The primary purpose of this study is to estimate the overall response rate (ORR), defined as partial response (PR) or better at any time during induction therapy. The success of the therapy will be determined by ORR with strong consideration given to the secondary endpoints of tolerability, duration of response, and quality of life (QOL).
All patients will be treated with the same experimental regimen. Several novel features are being explored: the substitution of cyclophosphamide for melphalan; once weekly AND subcutaneous bortezomib instead of standard twice weekly, intravenous dosing; and alternating bortezomib and lenalidomide in maintenance.
The investigators hypothesize that this regimen will prove to be tolerable and effective in inducing and maintaining remission in a patient population that is historically very difficult to treat, namely Multiple Myeloma (MM) patients who are too elderly or suffer comorbidities, such as renal insufficiency, that otherwise complicate aggressive therapies like autologous stem-cell transplantation (ASCT). In short, the investigators view this as the "Multiple Myeloma trial for non-trial candidates."
详细描述
A total of 35 patients will be accrued to this single arm, open label, phase II trial over a period of about 18 months, studying induction chemotherapy with VELCADE, cyclophosphamide and dexamethasone administered on an attenuated dosing schedule to accommodate non-candidates for high-dose chemotherapy with autologous stem cell transplantation - an often frail patient population. Maintenance therapy will follow with alternating lenalidomide and VELCADE. All patients should receive antiviral (zoster) prophylaxis, and peptic ulcer prophylaxis is recommended. Aspirin and/or anticoagulation are left to study physician discretion. All patients will be treated with the same experimental regimen. Several novel features are being explored: the substitution of cyclophosphamide for melphalan; once weekly AND subcutaneous bortezomib instead of standard twice weekly, intravenous dosing; and alternating bortezomib and lenalidomide in maintenance. The overarching aim is to preserve efficacy while minimizing toxicity and inconvenience to this often frail patient population.
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
- •Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- •Age ≥18 years at the time of signing the informed consent form.
- •Able to adhere to the study visit schedule and other protocol requirements.
- •Multiple Myeloma (MM) diagnosed according to the following standard criteria (all three criteria must be met):
- •Monoclonal plasma cells in bone marrow ≥10% and/or presence of biopsy-proven plasmacytoma
- •Laboratory tests meet the levels specified in the protocol
- •Measurable disease requiring systemic therapy.
- •No prior systemic therapy or radiation therapy active against myeloma lasting more than four weeks duration. Any prior therapy must be completed a minimum of 21 days before starting study drugs. Enrollment of subjects who require radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
- •Karnofsky performance status (KPS) of ≥ 60% at study entry.
- •In order to obtain lenalidomide, patients must be registered into the mandatory RevlimidREMS® program during the maintenance phase of therapy, and be willing and able to comply with the requirements of RevlimidREMS®
- •Female subjects must be postmenopausal for at least 1 year before the screening visit or surgically sterilized. If females are of childbearing potential, they must adhere to required pregnancy testing; male and female subjects must use specified effective birth control methods.
- •Patients should receive concomitant therapy with bisphosphonates, regardless of the presence of bony lesions, although study physicians may use their discretion based on presence of renal insufficiency or other mitigating factors.
排除标准
- •Abnormal laboratory tests within the ranges specified in the protocol
- •Serum creatinine will not be used to exclude patients. Patients on renal-replacement therapy (e.g., hemodialysis or peritoneal dialysis) will be eligible to participate.
- •Light-chain (AL) amyloidosis. Patients with secondary amyloidosis due to MM are eligible.
- •≥ Grade 2 peripheral neuropathy
- •Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any Electrocardiography (ECG) abnormality at screening must be documented by the investigator as not medically relevant.
- •Hypersensitivity to VELCADE, boron, mannitol, or any other component of protocol therapy.
- •Female subject is pregnant or lactating. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (b- hCG) pregnancy test result obtained during screening as specified in section 7.
- •Female patients who are lactating or have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on Day 1 before first dose of study drug, if applicable.
- •Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- •Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- •Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
- •Concurrent use of other anti-cancer agents or treatments
- •Known HIV positivity
- •Known active hepatitis A, B or C
研究组 & 干预措施
Velcade, cyclophosphamide, Revlimid
INDUCTION (28-day cycles for 8 cycles):
- VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15
- Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15
- Dexamethasone 40 mg PO days 1,8 and 15
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):
- Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21
- Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15
干预措施: Velcade (Drug)
Velcade, cyclophosphamide, Revlimid
INDUCTION (28-day cycles for 8 cycles):
- VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15
- Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15
- Dexamethasone 40 mg PO days 1,8 and 15
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):
- Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21
- Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15
干预措施: Cyclophosphamide (Drug)
Velcade, cyclophosphamide, Revlimid
INDUCTION (28-day cycles for 8 cycles):
- VELCADE 1.3 mg/m2 subcutaneously (SC) days 1, 8 and 15
- Cyclophosphamide 300 mg/m2 orally (PO) days 1, 8 and 15
- Dexamethasone 40 mg PO days 1,8 and 15
MAINTENANCE (28-day alternating cycles until stopped for toxicity, relapse or death):
- Odd cycles (9, 11, 13, etc.) lenalidomide 10 mg PO days 1-21
- Even cycles (10, 12, 14, etc.) VELCADE 1.3 mg/m2 SC days 1, 15
干预措施: Revlimid (Drug)
结局指标
主要结局
Overall Response Rate (ORR) During Induction Therapy
时间窗: Up to 8 months
Defined as percentage of patients achieving a partial response or better by International Myeloma Working Group (IMWG) standard criteria: IMWG: Complete Response (CR): negative immunofixation on the serum and urine, no soft tissue plasmacytomas and \<5% plasma cells in the bone marrow; stringent CR: CR+normal free light chain ratio, no clonal cells in bone marrow by immunohistochemistry or immunofluorescence; Very Good Partial Response: serum and urine M-protein detected by immunofixation but not electrophoresis, \>90% in serum M-protein+urine, M-protein level \<100 mg/24hour; Partial Response (PR): ≥50% decrease of serum and M-protein, 24 hour urinary M-protein decrease by ≥90% or \<200 mg/24hour.
次要结局
- Maximum Depth of Response During Induction Therapy(Up to 8 months)
- Median Progression-free Survival(4 years)
- QLQ-C30 Question 30(baseline, 3 months, 5 months)
- Risk Score as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool(Day 1)
- Severe Adverse Event Rate(Up to 3 years)
- Median Overall Survival(Up to 3 years)
- Maximum Depth of Response During Maintenance Therapy(Up to 3 years)
- Median Time to Response(Up to 8 months)
- QLQ-C30 Question 29(baseline, 3 months, 5 months)
- Median Duration of Response(From date of first confirmed response until date of disease progression or up to 3 years)
- Functionality as Assessed Using the Cancer and Leukemia Group B (CALGB) Geriatric Assessment Tool(baseline)