A Phase II Study of Thalidomide (THALOMID®), Clarithromycin (BIAXIN®), Lenalidomide(REVLIMID®), and Dexamethasone (DECADRON®) for Subjects With Newly Diagnosed Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Effect of Drug Combination on Multiple Myeloma
研究概览
简要总结
Study Objectives
- Evaluate the efficacy of the combination of thalidomide (Thalomid®), clarithromycin (Biaxin®), lenalidomide (Revlimid®), and dexamethasone (Decadron®) as an induction therapy for patients with newly diagnosed multiple myeloma (MM).
- Evaluate the efficacy of the addition of thalidomide (Thalomid®) to BiRD combination therapy as a therapy to increase the complete response rate for patients with newly diagnosed multiple myeloma.
- Evaluate the safety of the combination of clarithromycin, lenalidomide, dexamethasone, and thalidomide as a therapy for patients with newly diagnosed MM
详细描述
This phase II study is a treatment program for patients with newly diagnosed multiple myeloma. Up to 25 patients will be enrolled. Patients who sign consent and fulfill all eligibility criteria will be enrolled to receive the following treatment plan:
T-BiRD Therapy:
Cycles 1-4
- Thalidomide (50mg daily for days 1-7, thereafter 100mg daily for days 8-28 of the first 28 day cycle. Thalidomide will then be given at 100mg/daily for days 1-28 for each subsequent cycle)
- Clarithromycin (500mg twice daily for each 28 day cycle)
- Lenalidomide (25 mg daily days 1-21 of every 28 day cycle) and
- Dexamethasone (40 mg daily on day 1, 8, 15 and 22 of each 28 day cycle)
- Prophylactic medications will be given.
After completing 4 cycles
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
- •Subject must voluntarily sign and understand written informed consent.
- •Age > 18 years at the time of signing the consent form.
- •Histologically confirmed Salmon-Durie stage II or III MM. Stage I MM patients will be eligible if they display poor prognostic factors (ß2M ≥5.5 mg/L, plasma cell proliferation index ≥5%, albumin of less then 3.0, and unfavorable cytogenetics).
- •Newly diagnosed myeloma.
- •No anti-myeloma therapy within 14 days prior to initiation of study treatment except for corticosteroids with a maximum allowed dosage equivalent to three pulses of dexamethasone (40mg daily for 4 days equals one pulse). Patients may be receiving adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care.
- •Measurable disease as defined by > 1.0 g/dL serum monoclonal protein, >0.1 g/dL serum free light chains, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s).
- •Karnofsky performance status ≥70% (>60% if due to bony involvement of myeloma.
- •Able to take aspirin daily as prophylactic anticoagulation. (patients intolerant to ASA may use warfarin or low molecular weight heparin)
- •All study participants must be registered into the mandatory RevAssist® and S.T.E.P.S.® programs, and be willing and able to comply with the requirements of RevAssist® and the S.T.E.P.S.® programs.
- •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 prescribing lenalidomide and thalidomide (prescriptions must be filled within 7 days) 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 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy.
- •Life expectancy ≥ 3 months
- •Subjects must meet the following laboratory parameters:
- •Absolute neutrophil count (ANC) ≥1000 cells/mm3 (1.0 x 109/L)
- •Platelets count ≥ 75,000/mm3 (75 x 109/L)
- •Serum SGOT/AST <3.0 x upper limits of normal (ULN)
- •Serum SGPT/ALT <3.0 x upper limits of normal (ULN)
- •Serum creatinine <2.5 mg/dL (221 µmol/L)
- •Serum total bilirubin <2.0 mg/dL (34 µmol/L)
排除标准
- •Patients with non-secretory MM (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine).
- •Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ≥ 5 years.
- •Myocardial infarction within 6 months prior to enrollment , or NYHA(New York Hospital Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- •Pregnant or lactating females are ineligible.
- •Given the potential of the study drugs to trigger or worsen HIV viremia and the incidence of opportunistic infections inpatients infected with the HIV virus, HIV-1 or HIV-2 positive patients will be excluded. The interactions of HAART with study drugs have not been determined.
- •Active hepatitis B or hepatitis C infection.
- •Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
- •Any coexisting medical problem or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial.
- •Known hypersensitivity to dexamethasone, clarithromycin, lenalidomide, or thalidomide.
- •History of thromboembolic event within the past 6 months prior to enrollment.
研究组 & 干预措施
T-BiRD Therapy
All patients were treated with the same regimen, starting with T-BIRD therapy (Cycles 1-4).
After 4 cycles, Patients with disease progression will be taken off study. Patients who achieve maximum response will receive maintenance. Patients who achieve VGPR or PR will be given T-BiRD for 2 cycles (cycles 5-6). After 6 cycles of T-BiRD, Patients who achieve maximum response will receive maintenance; those with disease progression will be taken off study; all other patients will receive BIRD.
Patients who progress on BiRD will reinitiate T-BiRD. If disease progression continues after 2 cycles, patients will be taken off study.
Patients in CR/sCR or that achieve a plateau of disease for > 2 cycles on BiRD or T-BiRD therapy will receive maintenance.
干预措施: thalomid (Drug)
T-BiRD Therapy
All patients were treated with the same regimen, starting with T-BIRD therapy (Cycles 1-4).
After 4 cycles, Patients with disease progression will be taken off study. Patients who achieve maximum response will receive maintenance. Patients who achieve VGPR or PR will be given T-BiRD for 2 cycles (cycles 5-6). After 6 cycles of T-BiRD, Patients who achieve maximum response will receive maintenance; those with disease progression will be taken off study; all other patients will receive BIRD.
Patients who progress on BiRD will reinitiate T-BiRD. If disease progression continues after 2 cycles, patients will be taken off study.
Patients in CR/sCR or that achieve a plateau of disease for > 2 cycles on BiRD or T-BiRD therapy will receive maintenance.
干预措施: lenalidomide (Drug)
T-BiRD Therapy
All patients were treated with the same regimen, starting with T-BIRD therapy (Cycles 1-4).
After 4 cycles, Patients with disease progression will be taken off study. Patients who achieve maximum response will receive maintenance. Patients who achieve VGPR or PR will be given T-BiRD for 2 cycles (cycles 5-6). After 6 cycles of T-BiRD, Patients who achieve maximum response will receive maintenance; those with disease progression will be taken off study; all other patients will receive BIRD.
Patients who progress on BiRD will reinitiate T-BiRD. If disease progression continues after 2 cycles, patients will be taken off study.
Patients in CR/sCR or that achieve a plateau of disease for > 2 cycles on BiRD or T-BiRD therapy will receive maintenance.
干预措施: clarithromycin (Drug)
T-BiRD Therapy
All patients were treated with the same regimen, starting with T-BIRD therapy (Cycles 1-4).
After 4 cycles, Patients with disease progression will be taken off study. Patients who achieve maximum response will receive maintenance. Patients who achieve VGPR or PR will be given T-BiRD for 2 cycles (cycles 5-6). After 6 cycles of T-BiRD, Patients who achieve maximum response will receive maintenance; those with disease progression will be taken off study; all other patients will receive BIRD.
Patients who progress on BiRD will reinitiate T-BiRD. If disease progression continues after 2 cycles, patients will be taken off study.
Patients in CR/sCR or that achieve a plateau of disease for > 2 cycles on BiRD or T-BiRD therapy will receive maintenance.
干预措施: dexamethasone (Drug)
结局指标
主要结局
Effect of Drug Combination on Multiple Myeloma
时间窗: This was collected from patients for their duration on study treatment. Only the best response was recorded. Best responses were reported at any point of the study, from start of treatment up until removal of study, which occurred up to 57.4 cycles
Objective response rate, defined according to the International Myeloma Working Group (IMWG) criteria as greater then or equal to a Partial Response (PR). The best response was recorded. The IMWG criteria can be found here: imwg.myeloma.org/international-myeloma-working-group-imwg-uniform-response-criteria-for-multiple-myeloma/
次要结局
- Median Time to Maximum Response(from baseline to cycle with maximum response)
- Event Free Survival(from baseline to the time of first event that lead to removal from study (defined as progression, death, withdrawal of consent, or removal for toxicity))
- Progression Free Survival(From start of treatment, to the date of first progression)