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Predictive markers for personalized therapy in chronic lymphocytic leukemia

慢性淋巴细胞白血病个体化治疗的预测标记

基本信息

批准号：
10591089
负责人：
Jacob Soumerai
金额：
$ 28.59万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10591089
关键词：
17p Abbreviations Achievement Address Aftercare Anemia Antibodies BCL2 gene Biological Assay Biological Markers Biometry Bone Marrow Cancer Personalized Profiling by Deep Sequencing Chronic Lymphocytic Leukemia Clinical Clinical Research Clinical Trials Clonal Evolution Data Detection Development Development Plans Disease remission Doctor of Philosophy Ensure Evaluation Failure Fellowship Funding General Hospitals Globulins Goals Health Hematologist Kinetics Knowledge Lactate Dehydrogenase Lymphoma MS4A1 gene Massachusetts Medical Oncologist Medicine Mentors Mentorship Mission Mutation Patient Care Patient-Focused Outcomes Patients Persons Phase Positioning Attribute Procedures Public Health Recurrent disease Relapse Research Research Personnel Residual Neoplasm Resistance Retreatment Risk Risk Factors Sampling Scientific Advances and Accomplishments TP53 gene Technical Expertise Techniques Testing Therapeutic Time Training Training Activity Translations Treatment Efficacy Variant assay development biomarker development biomarker validation career career development clinical translation detection limit experience genomic predictors genomic signature high risk improved improved outcome inhibitor inhibitor therapy leukemia treatment medical schools novel therapeutic intervention peripheral blood personalized medicine phase II trial predictive marker predictive signature professor prognostic model programs prospective relapse patients resistance mechanism response biomarker skills success targeted sequencing therapy duration treatment duration tumor DNA

项目摘要

PROJECT SUMMARY/ABSTRACT Candidate. Jacob D. Soumerai, MD is an Assistant Professor of Medicine at Harvard Medical School (HMS) and Hematologist/Medical Oncologist at Massachusetts General Hospital (MGH) who conducts mentored clinical research in lymphoma and chronic lymphocytic leukemia (CLL). His goal over the next 5 years is to transition to an R01-funded, independent investigator leading a clinical trials and translational biomarker research program that advances the care of patients with lymphoma/CLL. Mentorship, Career Development, and Training Activities. To ensure his successful transition to independence, Dr. Soumerai developed a robust career development plan to address his training gaps through focused training/coursework and mentoring. His mentors are world-renowned experts in lymphoma and CLL with non-overlapping technical expertise directly related to Dr. Soumerai’s proposed K08 research plan and career objectives, and include Jeremy Abramson MD, Timothy Graubert MD and Andrew Zelenetz MD, PhD. Dr. Soumerai’s K08 career development plan will provide necessary training in translational biomarker assay development, advanced biostatistical techniques for biomarker research, regulatory requirements/procedures and clinical utility evaluation to develop validated biomarkers for clinical use. Research. Validated predictive markers for response are needed to develop personalized therapies and ultimately to improve the health and survival of people living with CLL. His central goal is to identify clinically validated predictive markers for response that help guide development of personalized CLL therapies. To achieve this goal, he will use his co-mentor’s trial of BCL2 inhibitor (BCL2i)-based therapy, which modifies therapy duration based on ΔMRD400 status (400-fold minimal residual disease (MRD) depletion over 4 months) to validate ΔMRD400 as a predictive marker to guide treatment duration to achieve undetectable MRD (uMRD) and identify high-risk patients (Aim 1). Next, he will use BCL2i retreatment efficacy data from his co-mentor’s trial to determine if ΔMRD400 status with prior BCL2i therapy, BALL risk factors for survival (B2-microglobulin, Anemia, LDH, time from Last therapy), or TP53 mutation/17p deletion can predict BCL2i retreatment success/failure (Aim 2). Finally, he will subject serial baseline/on-treatment patient samples from his co-mentor’s trial to PhasED-Seq/CAPP-Seq to identify genomic signatures that predict for failure to achieve uMRD, which might identify therapeutic vulnerabilities leading to novel therapeutic approaches (Aim 3). Completion of this proposal/training plan will position Dr. Soumerai with the necessary experience and skills to become an R01-funded independent investigator leading a clinical trials/translational biomarker research program in lymphoma/CLL.

项目总结/文摘