MC230818 Understanding the Mechanisms of Clonal and Non-Clonal Cytopenia Following CAR-T Therapy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 82
- 试验地点
- 7
- 主要终点
- Unexplained cytopenia
研究概览
简要总结
This clinical trial evaluates the impact of preexisting and therapy-emergent germline and somatic variants on cytopenia in patients with multiple myeloma or CD19 positive lymphoproliferative disorder (LPD) following chimeric antigen receptor T-cell (CAR-T) therapy. The most common adverse event after CAR-T therapy is lower than normal blood cells (cytopenia) and up to one third of patients experience cytopenia that last longer than 30 days post-infusion. Germline and somatic variants are changes in genes found using cancer genomic tests. Cancer genetic/genomic testing is a series of tests that find specific changes in cancer cells or in blood deoxyribonucleic acid. Identifying gene mutations may help identify the risk of cytopenia in patients with multiple myeloma or CD19 positive LPD following CAR-T therapy.
详细描述
PRIMARY OBJECTIVE:
I. Determine the preexisting and therapy-emergent germline and somatic variants associated with an increased risk of clonal and non-clonal cytopenia following CAR-T cell therapy on research basis.
SECONDARY OBJECTIVE:
I. Characterize the baseline transcriptomic signature associated with non-clonal and clonal cytopenia following CAR-T therapy on research basis.
OUTLINE:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 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
- •Age ≥ 18 years
- •Histologically or cytologically confirmed diagnosis of multiple myeloma (MM) as defined in International Myeloma Working Group (IMWG) criteria or a CD19+ lymphoproliferative disorder (LPD) as defined by 2016 World Health Organization (WHO) classification
- •Provide written informed consent
- •Willingness to provide mandatory bone marrow aspirate specimens for correlative research. All bone marrow aspirate samples are collected during a clinical procedure
- •Willingness to provide mandatory hair follicle or skin punch biopsy specimens (skin punch biopsy specimens will be obtained from Mayo Clinic Rochester patients only) for correlative research
- •Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- •Willingness to provide mandatory saliva or buccal swab sample for correlative research
排除标准
- •Ineligible for CAR-T therapy
- •Patients diagnosed with myeloid neoplasm before CAR-T therapy
研究组 & 干预措施
Supportive care (bone marrow aspiration, CFU)
Patients undergo bone marrow aspiration and hair, saliva, buccal swab, or skin sample collection up to 14 days prior to LD therapy. Patients undergo CFU on day 90 post-CAR-T therapy. Patients with unexplained cytopenia also undergo bone marrow aspiration for sequencing analysis on day 90 and at development of MN-pCT during CFU. Patients also undergo bone marrow aspiration at determination of clonal evolution or myeloid neoplasm if not done during CFU on day 90.
干预措施: Bone Marrow Aspiration (Procedure)
Supportive care (bone marrow aspiration, CFU)
Patients undergo bone marrow aspiration and hair, saliva, buccal swab, or skin sample collection up to 14 days prior to LD therapy. Patients undergo CFU on day 90 post-CAR-T therapy. Patients with unexplained cytopenia also undergo bone marrow aspiration for sequencing analysis on day 90 and at development of MN-pCT during CFU. Patients also undergo bone marrow aspiration at determination of clonal evolution or myeloid neoplasm if not done during CFU on day 90.
干预措施: Biospecimen Collection (Procedure)
Supportive care (bone marrow aspiration, CFU)
Patients undergo bone marrow aspiration and hair, saliva, buccal swab, or skin sample collection up to 14 days prior to LD therapy. Patients undergo CFU on day 90 post-CAR-T therapy. Patients with unexplained cytopenia also undergo bone marrow aspiration for sequencing analysis on day 90 and at development of MN-pCT during CFU. Patients also undergo bone marrow aspiration at determination of clonal evolution or myeloid neoplasm if not done during CFU on day 90.
干预措施: Genetic Counseling (Other)
Supportive care (bone marrow aspiration, CFU)
Patients undergo bone marrow aspiration and hair, saliva, buccal swab, or skin sample collection up to 14 days prior to LD therapy. Patients undergo CFU on day 90 post-CAR-T therapy. Patients with unexplained cytopenia also undergo bone marrow aspiration for sequencing analysis on day 90 and at development of MN-pCT during CFU. Patients also undergo bone marrow aspiration at determination of clonal evolution or myeloid neoplasm if not done during CFU on day 90.
干预措施: Electronic Health Record Review (Other)
Supportive care (bone marrow aspiration, CFU)
Patients undergo bone marrow aspiration and hair, saliva, buccal swab, or skin sample collection up to 14 days prior to LD therapy. Patients undergo CFU on day 90 post-CAR-T therapy. Patients with unexplained cytopenia also undergo bone marrow aspiration for sequencing analysis on day 90 and at development of MN-pCT during CFU. Patients also undergo bone marrow aspiration at determination of clonal evolution or myeloid neoplasm if not done during CFU on day 90.
干预措施: Follow-Up (Procedure)
Supportive care (bone marrow aspiration, CFU)
Patients undergo bone marrow aspiration and hair, saliva, buccal swab, or skin sample collection up to 14 days prior to LD therapy. Patients undergo CFU on day 90 post-CAR-T therapy. Patients with unexplained cytopenia also undergo bone marrow aspiration for sequencing analysis on day 90 and at development of MN-pCT during CFU. Patients also undergo bone marrow aspiration at determination of clonal evolution or myeloid neoplasm if not done during CFU on day 90.
干预措施: Genetic Testing (Other)
结局指标
主要结局
Unexplained cytopenia
时间窗: At day 90
Unexplained cytopenia will be defined per World Health Organization (WHO)-5 as a combination of any of the following: hemoglobin \< 12 g/dL in females, hemoglobin \< 13 g/dL in males, absolute neutrophil count \< 1.8 x 10\^9/L and platelets \< 150 x 10\^9/L. Logistic regression will be used to identify the presence or absence of baseline germline and somatic mutations associated with unexplained cytopenia. An odds ratio and 95% confidence interval will be reported.
Pathogenic and likely pathogenic germline and somatic variants associated with increased risk
时间窗: At baseline
The count and percentage of patients with the presence of somatic or germline variants will be reported. The number, type, and function of somatic variants will also be reported.
次要结局
- Development of myeloid neoplasm post-cytotoxic therapies (MN-pCT)(Up to 2 years)