AVM0703 combined with Non-Hodgkin's Lymphoma standard of care to enhance complete response rates without additional toxicities

AVM0703 与非霍奇金淋巴瘤护理标准相结合，可提高完全缓解率，且不会产生额外毒性

• 批准号: 10546563
• 负责人: Theresa Deisher
• 金额: $ 39.92万
• 依托单位: AVM BIOTECHNOLOGY, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-05 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546563
• 关键词: Acute; Adverse effects; Agammaglobulinaemia tyrosine kinase; Age; B-Cell NonHodgkins Lymphoma; Biotechnology; Blood; Body Weight decreased; Bone Marrow; Burkitt Lymphoma; Cancer Etiology; Cancerous; Cardiotoxicity; Cell Line; Cells; Chemotherapy-Oncologic Procedure; Clinical; Clinical Research; Clinical Trials; Combined Modality Therapy; Cyclophosphamide; DNA; Data; Death Rate; Desire for food; Dexamethasone; Diagnosis; Disease remission; Dose; Doxorubicin; Economic Burden; Elderly; Endotoxins; Evolution; Excipients; Exposure to; Feeling; Formulation; Frequencies; Genomics; Glucocorticoids; Goals; Growth; Health; Healthcare; Hour; In complete remission; Inbred BALB C Mice; Infusion procedures; Intravenous; Invaded; Lymphocyte; Lymphoma; Lymphoma cell; Malignant Neoplasms; Measurement; Modeling; Monoclonal Antibody CD20; Mus; Newly Diagnosed; Non-Hodgkin' s Lymphoma; Outcome; Package Insert; Patients; Pharmaceutical Preparations; Phase; Placebos; Population; Prednisone; Quality of life; Recurrence; Refractory; Regimen; Relapse; Reporting; Risk; Rogaine; Safety; Second Primary Cancers; Small Business Innovation Research Grant; Spleen; Therapeutic; Time; Toxic effect; Toxicology; Tumor Volume; Tyrosine Kinase Inhibitor; Vincristine; anti-CD20; base; cancer diagnosis; cancer therapy; chemotherapy; combinatorial; cost; efficacy study; experience; immune resistance; improved; inhibitor; innovation; large cell Diffuse non-Hodgkin' s lymphoma; mouse model; neurotoxicity; non-Hodgkin' s lymphoma patients; novel; novel strategies; novel therapeutics; older patient; patient population; patient subsets; pre-clinical; response; rituximab; side effect; sodium phosphate; standard of care; tositumomab; treatment strategy; tumor

PROJECT SUMMARY Non-Hodgkin’s Lymphoma (NHL) represents 4% of all cancer diagnosed in the U.S., and as many as 50% of patients will relapse within 2 years of diagnosis and treatment. The current standard of care is chemotherapy. For Diffuse Large B cell Lymphoma subtype (DLBCL) CHOP (cyclophosphamide- doxorubicin-vincristine-prednisone) is given in combination with an anti-CD20 monoclonal antibody, such as rituximab (R-CHOP). Unfortunately, chemotherapy requires numerous treatment cycles with challenging side effects and does not completely remove the cancerous lymphocytes, as indicated by the frequency of relapse. A drug that could reduce the lymphoma population and essentially increase the potency of the chemotherapy regimen (fewer lymphoma cells to the chemotherapy concentration) would have the potential to be synergistic as a treatment strategy. AVM0703, a proprietary formulation of high concentration dexamethasone developed by AVM Biotechnology, has been shown to control NHL growth in murine models. It also safely reduces lymphocytes following a single very high dose via one-hour infusion, in both pre-clinical and clinical settings. AVM0703 is currently the subject of a US-based clinical study in no-option, relapsed/refractory NHL patients and is distinguished from other investigative drugs in this ‘terminal no-option’ patient population by its absence of safety concerns with patients reporting feeling great, regaining appetite and energy, and durable response recorded. The goal of this project is to validate the combination of AVM0703 and standard DLBCL chemotherapy R-CHOP. This approach is expected to increase complete response rates and potentially reduce the required number of chemotherapy cycles, providing a more tolerable therapeutic option for newly diagnosed NHL patients. The feasibility of this approach will be validated in Phase I with the following aims: Aim 1) Evaluate the ability of AVM0703 in combination with R-CHOP to reduce R-CHOP cycles in an aggressive, immune-resistant murine B cell NHL model. Aim 2) Assessment of AVM0703 combination therapy with reduced dose R-CHOP to enhance outcomes in elderly patients. The Phase II project will further focus on efficacy studies, and a small clinical trial with newly diagnosed NHL patients to evaluate the effects of this novel therapeutic treatment approach.

项目摘要 非霍奇金的淋巴瘤（NHL）占美国诊断出的所有癌症的4％，多达50％ 患者将在诊断和治疗的2年内中继。当前的护理标准是 化学疗法。用于扩散的大B细胞淋巴瘤亚型（DLBCL）CHOP（环磷酰胺 - 阿霉素 - vincristine-prednisone）与抗CD20单克隆抗体相结合，例如 利妥昔单抗（R-Chop）。不幸的是，化学疗法需要许多挑战方面的治疗周期 效果，并不能完全清除取消的淋巴细胞，如缓解频率所示。 可以减少淋巴瘤群体并基本上增加化学疗法的药物 方案（较少的淋巴瘤细胞至化学疗法浓度）将具有协同作用 作为治疗策略。 AVM0703，高浓度地塞米松的专有公式 由AVM生物技术开发，已显示可控制鼠模型中的NHL生长。它也安全 通过一小时输注，在一次非常高剂量后，在临床前和临床上减少淋巴细胞 设置。目前，AVM0703是一项基于美国的临床研究的主题 患者并通过 它缺乏对报告感觉很好，恢复食欲和精力的患者的安全问题，以及 记录了持久的响应。该项目的目的是验证AVM0703和Standard的组合 DLBCL化学疗法R-CHOP。预计这种方法将提高完整的答复率，并且 有可能减少所需数量的化学疗法周期，提供更可耐受的治疗选择 对于新诊断的NHL患者。这种方法的可行性将在第一阶段验证 以下目的：目标1）评估AVM0703与R-Chop结合使用R-Chop的能力 在侵略性，抗性鼠B细胞NHL模型中循环。目标2）评估AVM0703 结合疗法与剂量R-CHOP减少，以增强老患者的结局。 II期 项目将进一步关注有效性研究，以及针对新诊断的NHL患者进行的小型临床试验 评估这种新型治疗方法的影响。