Phase I/II clinical trial of in-house BCMA CAR T-cell therapy and opaganib in ultrahigh risk multiple myeloma
About This Grant
Our long-term goal is to develop novel therapeutic approaches to improve the outcomes and survival of patients with ultrahigh risk multiple myeloma (uHRMM). uHRMM encompasses 15-20% of all multiple myeloma diagnoses and is associated with a very poor prognosis. The median overall survival for patients with uHRMM is only about 2 years, and a significant portion of patients with uHRMM die within 6-12 months of the diagnosis. Autologous hematopoietic stem cell transplantation does not provide a sustained response for patients with uHRMM, highlighting an unmet need to develop more effective therapeutic approaches for this population of patients. In this application, we describe a protocol in which we will manufacture in-house BCMA CART-cells using a closed system device, and treat uHRMM patients with BCMA CART-cells for consolidation following standard induction therapy, Additionally, to further improve the efficacy of BCMA CART-cell therapy, we propose the use of the sphingosine kinase 2 inhibitor opaganib after CAR T-cell infusion. Sphingolipid metabolism is increasingly being recognized as a key pathway in tumor biology and anti-tumor immunity. Sphingosine kinases (SK1 and SK2) offer a potential target for modulating tumor cell proliferation and apoptosis, as well as immune responses. We recently found that SK2 plays a critical but suppressive role in CD8 T-cell-mediated anti-tumor activity. CD8 T-cells isolated from SK2-1 - KO mice were more proliferative and more cytotoxic against myeloma cells. Compared to CART-cells generated from WT mice, anti-BCMA CART-cells generated from SK2-1 - KO mice exhibited enhanced anti-myeloma activities in vivo in our preclinical CAR T mouse model, Moreover, the combination of opaganib and BCMA CART-cell therapy resulted in much improved tumor control in our NSG myeloma xenograft CAR T mouse model, The obiective of this application is to determine the safety and preliminary efficacy of BCMA CART-cell therapy in combination with SK2 inhibition in the treatment of uHRMM. Our central hypothesis is that opaganib, administered following CART therapy, will enhance CART-cell function and reduce CART-cell exhaustion, resulting in a deeper and more sustained response for patients with uHRMM. We have two specific aims. Aim 1 is to perform a phase lb clinical trial to determine the safety, pharmacokinetics, and pharmacodynamics of opaganib in combination with in-house BCMA CART cell therapy in uHRMM following standard induction therapy, Up to 18 patients will be enrolled in phase lb study. Aim 2 is to perform a phase II clinical trial to determine the preliminary efficacy of opaganib in combination with inhouse BCMA CAR T cell therapy in uHRMM. Up to 21 additional patients will be enrolled at the recommended phase 2 dose to confirm safety and to investigate preliminary efficacy in this population of patients. We anticipate that this clinical trial will have significant implications for the treatment of uHRMM. The proposed studies constitute a focused approach for developing a novel treatment for patients with uHRMM, a disease with a high unmet clinical need. If positive, these data will provide justification for a larger, multi-center phase Ill study. Project Summary/Abstract
Grant Summary
Phase I/II clinical trial of in-house BCMA CAR T-cell therapy and opaganib in ultrahigh risk multiple myeloma is a NCI - National Cancer Institute grant providing up to $629K for university, nonprofit, healthcare org. Applications are due 2031-07-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $629K
2031-07-31
- 1Confirm your organization is eligible for Phase I/II clinical trial of in-house BCMA CAR T-cell therapy and opaganib in ultrahigh risk multiple myeloma from NCI - National Cancer Institute, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NCI - National Cancer Institute before the deadline.
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Phase I/II clinical trial of in-house BCMA CAR T-cell therapy and opaganib in ultrahigh risk multiple myeloma: Frequently Asked Questions
Who is eligible for the Phase I/II clinical trial of in-house BCMA CAR T-cell therapy and opaganib in ultrahigh risk multiple myeloma?
Phase I/II clinical trial of in-house BCMA CAR T-cell therapy and opaganib in ultrahigh risk multiple myeloma is offered by NCI - National Cancer Institute and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Phase I/II clinical trial of in-house BCMA CAR T-cell therapy and opaganib in ultrahigh risk multiple myeloma provide?
Phase I/II clinical trial of in-house BCMA CAR T-cell therapy and opaganib in ultrahigh risk multiple myeloma provides up to $629K per award from NCI - National Cancer Institute. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Phase I/II clinical trial of in-house BCMA CAR T-cell therapy and opaganib in ultrahigh risk multiple myeloma deadline?
Applications for Phase I/II clinical trial of in-house BCMA CAR T-cell therapy and opaganib in ultrahigh risk multiple myeloma are due 2031-07-31 (open). Because deadlines can change, verify the date with the funder, NCI - National Cancer Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Phase I/II clinical trial of in-house BCMA CAR T-cell therapy and opaganib in ultrahigh risk multiple myeloma?
To apply for Phase I/II clinical trial of in-house BCMA CAR T-cell therapy and opaganib in ultrahigh risk multiple myeloma, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NCI - National Cancer Institute.