A Personalized Vaccine for the Immune Prevention of Multiple Myeloma
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This early phase I trial studies the side effects of personalized vaccine in treating patients with smoldering multiple myeloma. Vaccines made from a person's blood and bone marrow may help the body build an effective immune response to kill cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To demonstrate that developing a custom vaccine for smoldering multiple myeloma (SMM) is feasible.
II. To show that a custom peptide-based vaccine in smoldering multiple myeloma is safe.
SECONDARY OBJECTIVES:
I. To determine the intensity and longevity of antigen specific T-cell mediated immune responses to the neoantigen vaccine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Adult patients with intermediate or high-risk smoldering multiple myeloma (SMM) are eligible
- •Patients must have histologically confirmed SMM based on the following criteria. Both criteria must be met: (a) Serum monoclonal protein (IgG or IgA) >= 3 g/dL or urinary monoclonal protein >=500 mg per 24 hours and/or clonal bone marrow plasma cells more or equal to 10% (b) Absence of myeloma defining events or amyloidosis
- •Additionally, patients must meet criteria for intermediate or high risk of progression to multiple myeloma by Programa para el Estudio de la Terapeutica en Hemopatía Maligna (PETHEMA) criteria (patients must have at least 1 risk factors present):
- •>= 95% abnormal plasma cells/total plasma cells in bone marrow compartment. (This is measured as a percentage of the total abnormal versus normal plasma cells in the bone marrow compartment using standard flow cytometry of the bone marrow aspirate. Having >= 95% abnormal plasma cells/total plasma cells constitutes a risk factor for progression to multiple myeloma by PETHEMA criteria)
- •Immunoparesis (The patient having low uninvolved immunoglobulins in peripheral blood, for example if a patient has IgA smoldering multiple myeloma, then either having a low IgM and/or low IgG will qualify as a risk factor for progression to multiple myeloma) *1 of 2 risk factors: intermediate risk for progression at a rate of ~50% at 5 years *2 of 2 risk factors: high risk for progression at a rate of 72% at 5 years
- •Creatinine clearance >= 40 ml/min using the modification of diet in renal disease (MDRD) equation
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
- •Hemoglobin >= 10 g/dL
- •Platelet count >= 50 x 10^9/L
- •Platelet and blood transfusions are allowed on protocol. Growth factors, including granulocyte colony stimulating factors and erythropoietin are allowed
- •Bilirubin < 1.5 x the upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x ULN
- •Subjects must be able to give informed consent
排除标准
- •Evidence of myeloma defining events due to underlying plasma cell proliferative disorder meeting at least one of the following
- •Hypercalcemia: 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/min or serum creatinine > 2 mg/dL
- •Anemia: hemoglobin value < 10 g/dL
- •Bone lesions: one or more osteolytic lesions on skeletal radiography, computerized tomography (CT) or 2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography CT (PET-CT)
- •Prior or concurrent systemic treatment for SMM
- •Bisphosphonates are permitted
- •Treatment with corticosteroids is not permitted (allowed for physiologic doses)
- •Radiotherapy is not permitted
- •Prior treatment for smoldering multiple myeloma with chemotherapy agents approved for the treatment of multiple myeloma is not permitted
- •Plasma cell leukemia
- •Pregnant or lactating females
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- •Has a known history of active TB (Bacillus tuberculosis)
- •Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
- •Has an active infection requiring systemic therapy
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 60 days after the last dose of trial treatment
- •Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- •Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
研究组 & 干预措施
Stage I (personalized vaccine)
Patients undergo collection of blood and bone marrow for making the vaccine. Patients then receive personalized vaccine SC on days 1 and 15 of cycles 1-2 and on day 1 of cycles 3-6. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Biopsy Specimen Radiography (Procedure)
Stage I (personalized vaccine)
Patients undergo collection of blood and bone marrow for making the vaccine. Patients then receive personalized vaccine SC on days 1 and 15 of cycles 1-2 and on day 1 of cycles 3-6. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Vaccine Therapy (Biological)
Stage II (personalized vaccine, lenalidomide)
Patients undergo collection of blood and bone marrow for making the vaccine. Patients then receive personalized vaccine SC on days 1 and 15 of cycles 1-2 and on day 1 of cycles 3-6. Patients also receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Biopsy Specimen Radiography (Procedure)
Stage II (personalized vaccine, lenalidomide)
Patients undergo collection of blood and bone marrow for making the vaccine. Patients then receive personalized vaccine SC on days 1 and 15 of cycles 1-2 and on day 1 of cycles 3-6. Patients also receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Lenalidomide (Drug)
Stage II (personalized vaccine, lenalidomide)
Patients undergo collection of blood and bone marrow for making the vaccine. Patients then receive personalized vaccine SC on days 1 and 15 of cycles 1-2 and on day 1 of cycles 3-6. Patients also receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Vaccine Therapy (Biological)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 12 months
Feasibility assessed by the proportion of participants for whom the vaccine is successfully developed and ready to administer
时间窗: Within 12 weeks
次要结局
- Duration of response(Up to 12 months)
- Intensity and longevity of antigen specific T-cell mediated immune responses to the neoantigen vaccine(Up to 12 months)
- Clinical benefit rate (minor response or better)(After 6 cycles (168 days))
- Time to progression(Up to 18 months)
- Overall survival(Up to 12 months)