A Phase 1 Study of VAC85135, a Neoantigen Vaccine Regimen, Concurrently Administered With Ipilimumab for the Treatment of Myeloproliferative Neoplasms
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 7
- 主要终点
- Number of Participants With Dose-limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study is to evaluate the safety of VAC85135 administered with ipilimumab for the treatment of myeloproliferative neoplasms (MPNs).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Be positive for a CALR (calreticulin) mutation: Type 1 or Type 2; Type 1-like, or Type 2-like may be considered with Sponsor approval; or positive for the JAK2V617F (Janus kinase 2 with valine 617 to phenylalanine mutation) mutation with HLA-A02:01 (human leukocyte antigens) per medical history or local testing
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 or 2
- •Have the following hematologic laboratory values: Leukocytes greater than or equal to (>=) 1.5*10^9 per liter, Neutrophils >=1.0*10^9 per liter, Platelets >=20*10^9 per liter, Hemoglobin greater than (>) 7 gram per deciliter (g/dL)
- •Have the following chemistry laboratory values: Alanine aminotransferase (ALT): less than or equal to (<=) 3*upper limit of normal (ULN), Aspartate aminotransferase (AST): <=3*ULN, Total bilirubin: <=1.5*ULN, and glomerular filtration rate >=40 milliliter per minute (mL/min)
- •A female participant of childbearing potential must agree to all the following during the study and for 6 months after the last dose of study treatment: use a barrier method of contraception, use a highly effective preferably user-independent method of contraception, not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction, not plan to become pregnant, not to breast-feed
- •A male participant must agree to all the following during the study and for 90 days after the last dose of study treatment: wear a condom when engaging in any activity that allows for passage of ejaculate to another person, not to father a child, not to donate sperm or freeze for future use for the purpose of reproduction
排除标准
- •History of any significant medical condition per investigators judgment (example: severe asthma/chronic obstructive pulmonary disease (COPD), poorly regulated heart condition, insulin dependent diabetes mellitus)
- •Serious known clinically relevant allergies or earlier anaphylactic reactions
- •Currently pregnant or breastfeeding
- •Prior treatment with any Janus kinase 1/2 (JAK1/2) inhibitor
- •Known sensitivity or contraindications to the use of Ipilimumab per local prescribing information
研究组 & 干预措施
Dose Escalation
Participants with essential thrombocythemia (ET) and myelofibrosis (MF) will receive VAC85135 target dose intramuscular (IM) injection in the safety lead-in cohort (Cohort 0). Participants in subsequent cohorts will receive VAC85135 target dose IM injection along with ipilimumab intravenous (IV) infusion. Ipilimumab dose may be escalated based on dose limiting toxicity (DLT) observations.
干预措施: VAC85135 (Biological)
Dose Escalation
Participants with essential thrombocythemia (ET) and myelofibrosis (MF) will receive VAC85135 target dose intramuscular (IM) injection in the safety lead-in cohort (Cohort 0). Participants in subsequent cohorts will receive VAC85135 target dose IM injection along with ipilimumab intravenous (IV) infusion. Ipilimumab dose may be escalated based on dose limiting toxicity (DLT) observations.
干预措施: Ipilimumab (Drug)
Dose Expansion
Participants with polycythemia vera (PV) or post-polycythemia vera myelofibrosis, ET and MF will receive VAC85135 target dose IM injection with ipilimumab IV infusion at the dose(s) determined by study evaluation team (SET).
干预措施: VAC85135 (Biological)
Dose Expansion
Participants with polycythemia vera (PV) or post-polycythemia vera myelofibrosis, ET and MF will receive VAC85135 target dose IM injection with ipilimumab IV infusion at the dose(s) determined by study evaluation team (SET).
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Number of Participants With Dose-limiting Toxicity (DLT)
时间窗: Baseline (Day 1) up to Day 78
Number of participants with a DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. Toxicities will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 79 weeks
Number of participants with AEs will be reported. An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical product. AEs will be graded as Grade 1: Mild- asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate- minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4- Life-threatening consequences- urgent intervention indicated; Grade 5: Death related to AE.
次要结局
- Number of Participants With Antigen-specific T-cell response(Up to end of treatment (EOT) (Up to 64 weeks))
- Number of Participants With Peripheral Blood Mutant Calreticulin (mutCALR) and Janus Kinase 2 With V617F Mutation (JAK2V617F) Allele Burden(Up to end of treatment (EOT) (Up to 64 weeks))
- Number of Participants With Transfusion Burden(Up to end of treatment (EOT) (Up to 64 weeks))
- Number of Participants With Patient-reported Symptoms on Therapy(Up to end of treatment (EOT) (Up to 64 weeks))
- Number of Participants With Overall Response per Revised Response Criteria by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) Consensus Report(Up to 79 weeks)
- Number of Participants Disease Response at Weeks 24, 48 and End of Treatment (EOT) per Modified IWG-MRT Criteria(Weeks 24, 48 and EOT (64 weeks))
- Time to Progression of Myeloproliferative Neoplasms (MPNs)(Up to end of treatment (EOT) (Up to 64 weeks))
- Time to Initiation of Next Therapy(Up to 79 weeks)