A Phase I Study of Safety, Tolerability and Immunological Effects of SVN53-67/M57-KLH in Patients With Multiple Myeloma Receiving Lenalidomide Maintenance Therapy
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 18
- 试验地点
- 4
- 主要终点
- Toxicity profile of the SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant plus sargramostim, given before or after the start of lenalidomide maintenance
研究概览
简要总结
This phase I trial studies the safety of SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant together with sargramostim in treating patients with newly diagnosed multiple myeloma who are receiving lenalidomide maintenance therapy. Vaccines made from survivin peptide may help the body build an effective immune response to kill cancer cells that express survivin. Incomplete Freund's adjuvant may help stimulate the body's immune response to a vaccine treatment. Colony-stimulating factors, such as sargramostim, may increase the production of blood cells. Lenalidomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant and sargramostim before or after the start of lenalidomide maintenance therapy may be a better treatment for multiple myeloma.
详细描述
PRIMARY OBJECTIVES:
I. To determine the toxicity profile of the SVN53-67/M57-KLH peptide (SVN53-67/M57-KLH peptide vaccine) in Montanide ISA 51 (incomplete Freund's adjuvant) plus GM-CSF (sargramostim) (vaccine), given before or after the start of lenalidomide maintenance in patients with multiple myeloma.
SECONDARY OBJECTIVES:
I. To measure the immune responses induced by SVN53-67/M57-KLH with Montanide ISA 51 plus GM-CSF, either alone or with lenalidomide maintenance added either before or after the vaccine.
TERTIARY OBJECTIVES:
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
- •Able to adhere to the study visit schedule and other protocol requirements
- •Patients with newly diagnosed multiple myeloma who have at least a partial response after induction therapy based on the International Working Group (IWG) Uniform Response Criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry
- •Must be free of systemic infection; subjects with active infections (whether or not they require antibiotic therapy) may be eligible after complete resolution of the infection; subjects on antibiotic therapy must be off antibiotics for at least 7 days before beginning treatment
- •Absolute neutrophil count >= 750/mm^3
- •Platelet count >= 30,000/mm^3
- •Creatinine clearance >= 30 mL/minutes
- •Total bilirubin =< 2 mg/dL
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x upper limit of normal (ULN)
- •All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS)®, and be willing and able to comply with the requirements of the Revlimid REMS®
- •Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program
- •Able to take aspirin (81 or 325 mg) daily for prophylactic anticoagulation (patients intolerant to acetylsalicylic acid, ASA, may use warfarin or low molecular weight heparin or other anticoagulants as deemed appropriate by physician)
- •Disease free of prior malignancies for > 2 years with exception of currently treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
- •All study participants must have one of the HLA alleles: HLA-A*02, HLA-A*03, HLAA*11, or HLA-A*24
- •Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
排除标准
- •Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
- •Pregnant or breast feeding females; (lactating females must agree not to breast feed while taking lenalidomide)
- •Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study as determined by the Principal Investigator
- •Chemotherapy, immunotherapy, radiotherapy, radiosurgery, interferon (e.g. Intron-A®), allergy desensitization injections, growth factors (e.g. Procrit®, Aranesp®, Neulasta®), interleukins (e.g. Proleukin®) or any investigational therapeutic medication within 4 weeks of study entry
- •Known hypersensitivity to thalidomide, lenalidomide, Keyhole Limpet Hemocyanin (KLH), or granulocyte colony-macrophage stimulating factor (GM-CSF)
- •The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
- •Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are seropositive because of hepatitis B virus vaccine are eligible
- •Any prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy or autoimmune disorders with visceral involvement
- •Patients with a known diagnosis of plasma cell leukemia
- •Systemic corticosteroid therapy > 2 mg of dexamethasone or equivalent per day at study entry
- •Patients had prior autologous or allogeneic stem cell transplant; prior stem cell collection is allowed
- •Life expectancy less than 4 months
研究组 & 干预措施
Group A (vaccine and week-4 lenalidomide maintenance therapy)
Patients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC every 2 weeks at weeks 0, 2, 4, and 6 for up to 4 doses and then receive a booster in week 12. Beginning in week 4, patients receive lenalidomide maintenance therapy PO QD in the absence of disease progression or unacceptable toxicity.
干预措施: Lenalidomide (Drug)
Group B (vaccine and week-0 lenalidomide maintenance therapy)
Patients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC every 2 weeks at weeks 4, 6, 8, and 10 for up to 4 doses and then receive a booster in week 16. Beginning in week 0, patients receive lenalidomide maintenance therapy PO QD in the absence of disease progression or unacceptable toxicity.
干预措施: Lenalidomide (Drug)
Group A (vaccine and week-4 lenalidomide maintenance therapy)
Patients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC every 2 weeks at weeks 0, 2, 4, and 6 for up to 4 doses and then receive a booster in week 12. Beginning in week 4, patients receive lenalidomide maintenance therapy PO QD in the absence of disease progression or unacceptable toxicity.
干预措施: Incomplete Freund's Adjuvant (Biological)
Group A (vaccine and week-4 lenalidomide maintenance therapy)
Patients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC every 2 weeks at weeks 0, 2, 4, and 6 for up to 4 doses and then receive a booster in week 12. Beginning in week 4, patients receive lenalidomide maintenance therapy PO QD in the absence of disease progression or unacceptable toxicity.
干预措施: Sargramostim (Biological)
Group A (vaccine and week-4 lenalidomide maintenance therapy)
Patients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC every 2 weeks at weeks 0, 2, 4, and 6 for up to 4 doses and then receive a booster in week 12. Beginning in week 4, patients receive lenalidomide maintenance therapy PO QD in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Group A (vaccine and week-4 lenalidomide maintenance therapy)
Patients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC every 2 weeks at weeks 0, 2, 4, and 6 for up to 4 doses and then receive a booster in week 12. Beginning in week 4, patients receive lenalidomide maintenance therapy PO QD in the absence of disease progression or unacceptable toxicity.
干预措施: SVN53-67/M57-KLH Peptide Vaccine (Biological)
Group B (vaccine and week-0 lenalidomide maintenance therapy)
Patients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC every 2 weeks at weeks 4, 6, 8, and 10 for up to 4 doses and then receive a booster in week 16. Beginning in week 0, patients receive lenalidomide maintenance therapy PO QD in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Group B (vaccine and week-0 lenalidomide maintenance therapy)
Patients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC every 2 weeks at weeks 4, 6, 8, and 10 for up to 4 doses and then receive a booster in week 16. Beginning in week 0, patients receive lenalidomide maintenance therapy PO QD in the absence of disease progression or unacceptable toxicity.
干预措施: SVN53-67/M57-KLH Peptide Vaccine (Biological)
Group B (vaccine and week-0 lenalidomide maintenance therapy)
Patients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC every 2 weeks at weeks 4, 6, 8, and 10 for up to 4 doses and then receive a booster in week 16. Beginning in week 0, patients receive lenalidomide maintenance therapy PO QD in the absence of disease progression or unacceptable toxicity.
干预措施: Incomplete Freund's Adjuvant (Biological)
Group B (vaccine and week-0 lenalidomide maintenance therapy)
Patients receive SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant SC and sargramostim SC every 2 weeks at weeks 4, 6, 8, and 10 for up to 4 doses and then receive a booster in week 16. Beginning in week 0, patients receive lenalidomide maintenance therapy PO QD in the absence of disease progression or unacceptable toxicity.
干预措施: Sargramostim (Biological)
结局指标
主要结局
Toxicity profile of the SVN53-67/M57-KLH peptide vaccine in incomplete Freund's adjuvant plus sargramostim, given before or after the start of lenalidomide maintenance
时间窗: Up to 24 weeks
The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be used to evaluate toxicity. The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category and grade. The frequency of toxicities will also be tabulated for the regimen estimated to be the regimen-limiting toxicity.
次要结局
- Immune response using interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) and multimer assays(Up to 24 weeks)