A Phase 1/1b Multicenter, Open Label Study to Evaluate the Safety of UF-KURE19 Cells in Patients With B Cell Non-Hodgkin Lymphomas
Overview
- Phase
- Phase 1
- Intervention
- UF-KURE19 CAR-T cells
- Conditions
- Non Hodgkin Lymphoma
- Sponsor
- David Wald
- Enrollment
- 21
- Locations
- 6
- Primary Endpoint
- Phase 1: Recommended dose(s) of UF-KURE19 CAR-T Cells
- Status
- Active, Not Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
This study seeks to determine the safety and efficacy of the infusion of autologous CD19 CAR-T cells that are manufactured using an ultra-fast process.
Detailed Description
This treatment uses T cells already present in the participant's body that have been modified outside of the body by a lentivirus and then returned by an infusion to target the cancer. Lentivirus is a family of viruses that can be used by scientists to alter cells. The specific type of cells that will be used is called UF-KURE19 chimeric antigen receptor T cells (CAR-T cells). The CAR-T cells that will be reinfused into the body are modified using a lentivirus that is no longer active. The investigators are evaluating UF-KURE19 because it uses a process that is shorter than other approved CAR-T cells. While the shorter manufacture time can be an advantage, the safety of this approach has not been demonstrated.
Investigators
David Wald
IND Holder
Case Comprehensive Cancer Center
Eligibility Criteria
Inclusion Criteria
- •Phase 1 Cohort:
- •Inclusion Criteria:
- •Male or female patients aged 18 years or older.
- •Participants must have histologically confirmed, CD19 positive (by IHC or flow cytometry) NHL that meets at least one of the following treatment indications.
- •Relapsed after 2 or more lines of chemotherapy, (or)
- •Refractory to chemotherapy, defined as: Progressive disease while receiving last chemotherapy, or Persistent disease after first line chemotherapy treatment with curative intent or stable disease lasting ≤6 months after last chemotherapy, or relapse within 6 months of last chemotherapy, or disease progression or relapse ≤12 months after prior autologous stem cell transplant, (or)
- •Relapsed disease that is ineligible to receive hematopoietic stem cell transplantation due to comorbidities or age or patient preference.
- •ECOG Performance status ≤
- •At least one measurable lesion according to Lugano Revised Response Criteria for Malignant Lymphoma.
- •Minimum of 2 weeks since prior radiation therapy or systemic therapy to treat malignancy at the time of leukapheresis.
Exclusion Criteria
- •The presence of any of the following will exclude a subject from study enrollment:
- •Autologous stem cell transplant within 6 weeks of informed consent.
- •History of allogeneic hematopoietic stem cell transplantation.
- •Active central nervous system or leptomeningeal involvement by lymphoma. Subjects with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal CASE 2422 Page 37 Version 13 02.03.2025 involvement must be in a documented remission by CSF evaluation and contrastenhanced MRI imaging for at least 90 days prior to registration.
- •Second active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast).
- •Less than 28 days elapsed between prior treatment with investigational agent(s) and leukapheresis.
- •New York Heart Association class III-IV congestive heart failure. Cardiovascular disorders including unstable angina pectoris, clinically significant cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic attack, or other ischemic event) within 6 months prior to registration.
- •Known human immunodeficiency virus infection or acquired immunodeficiency syndrome related illness.
- •Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
- •Evidence of myelodysplastic syndrome or cytogenetic abnormality indicative of myelodysplasia on the most recent bone marrow biopsy prior to initiation of therapy.
Arms & Interventions
UF-KURE19 CAR-T cell infusion
The safety and manufacturing feasibility of UF-KURE19 will be determined with up to 10 patients being enrolled. Lymphodepleting therapy will begin on Days -4 to -2 with each weight category of participants receiving 30mg/m2/IV of Fludarabine and 500mg/m2/IV of Cyclophosphamide regardless of the level of UF-KURE19 CAR-T cell dosing. Dosing: Participants greater than or equal to 50 kg: * Level -1: 10 x 10\^6 UF-KURE19 CAR-T Cell Dose (CAR positive cells) * Level 1 : 17.5 x 10\^6 UF-KURE19 CAR-T Cell Dose Participants less than 50 kg: * Level -1: 6.5 x 10\^6 UF-KURE19 CAR-T Cell Dose * Level 1: 11.5 x 10\^6 UF-KURE19 CAR-T Cell Dose
Intervention: UF-KURE19 CAR-T cells
UF-KURE19 CAR-T cell infusion
The safety and manufacturing feasibility of UF-KURE19 will be determined with up to 10 patients being enrolled. Lymphodepleting therapy will begin on Days -4 to -2 with each weight category of participants receiving 30mg/m2/IV of Fludarabine and 500mg/m2/IV of Cyclophosphamide regardless of the level of UF-KURE19 CAR-T cell dosing. Dosing: Participants greater than or equal to 50 kg: * Level -1: 10 x 10\^6 UF-KURE19 CAR-T Cell Dose (CAR positive cells) * Level 1 : 17.5 x 10\^6 UF-KURE19 CAR-T Cell Dose Participants less than 50 kg: * Level -1: 6.5 x 10\^6 UF-KURE19 CAR-T Cell Dose * Level 1: 11.5 x 10\^6 UF-KURE19 CAR-T Cell Dose
Intervention: Fludarabine
UF-KURE19 CAR-T cell infusion
The safety and manufacturing feasibility of UF-KURE19 will be determined with up to 10 patients being enrolled. Lymphodepleting therapy will begin on Days -4 to -2 with each weight category of participants receiving 30mg/m2/IV of Fludarabine and 500mg/m2/IV of Cyclophosphamide regardless of the level of UF-KURE19 CAR-T cell dosing. Dosing: Participants greater than or equal to 50 kg: * Level -1: 10 x 10\^6 UF-KURE19 CAR-T Cell Dose (CAR positive cells) * Level 1 : 17.5 x 10\^6 UF-KURE19 CAR-T Cell Dose Participants less than 50 kg: * Level -1: 6.5 x 10\^6 UF-KURE19 CAR-T Cell Dose * Level 1: 11.5 x 10\^6 UF-KURE19 CAR-T Cell Dose
Intervention: Cyclophosphamide
Outcomes
Primary Outcomes
Phase 1: Recommended dose(s) of UF-KURE19 CAR-T Cells
Time Frame: Up to 28 days after treatment
Safety will be assessed by the number of DLT experienced at the target dose which is hypothesized to be less than 33%.
Phase 1: Toxicities associated with the target dose of UF-KURE19 CAR-T Cells
Time Frame: Up to 12 months after treatment
Toxicities will be reported as specific adverse events as a result of the target dose of UF-KURE19 CAR-T Cells. An adverse event (AE) is any unfavorable or unintended event, physical or psychological, associated with a research study, which causes harm or injury to a research participant as a result of the participant's involvement in a research study.
Phase 1b: Toxicities associated with the target dose of UFKURE19 in patients with Relapsed or Refractory Large B-cell Lymphoma (LBCL).
Time Frame: Up to 12 months after treatment
Phase 1b: Complete response rate (CRR) with UF-KURE19 in patients with Relapsed or Refractory LBCL.
Time Frame: Up to 12 months after treatment
Phase 1b: Objective response rate (ORR, CR + PR) with UF-KURE19 in patients with Relapsed or Refractory LBCL.
Time Frame: Up to 12 months after treatment
Phase 1b: CRR in double/triple hit lymphoma (DHL/THL) patients treated with first-line standard of care chemoimmunotherapy PLUS early intervention of UFKURE19.
Time Frame: Up to 12 months after treatment
Secondary Outcomes
- Phase 1: Success rate of semi-automated CAR-T manufacturing process(Up to 2 weeks after culture of UF-KURE19 CAR-T cells)
- Phase 1: Objective response rates per Lugano Revised Response Criteria for Malignant Lymphoma after treatment with UF-KURE19 in patients with relapsed or refractory non-Hodgkin lymphoma(Up to 12 months after treatment)
- Phase 1: Complete response rates per Lugano Revised Response Criteria for Malignant Lymphoma after treatment with UF-KURE19 in patients with relapsed or refractory non-Hodgkin lymphoma(Up to 12 months after treatment)
- Phase 1b cohort of Relapsed or Refractory LBCL: duration of response in patients treated with UF-KURE19(Up to 12 months after treatment)
- Phase 1b cohort of Relapsed or Refractory Large B cell Lymphoma(LBCL): Overall survival in patients treated with UF-KURE19(Up to 12 months after treatment)
- Phase 1b cohort of Relapsed or Refractory LBCL: Progression-free survival in patients treated with UF-KURE19(Up to 12 months after treatment)
- Phase 1b cohort of Relapsed or Refractory LBCL: Manufacturing success rate(Up to 2 weeks after culture of UF-KURE19 CAR-T cells)
- Phase 1b cohort of DHL/THL: PFS in DHL/THL patients treated with first-line standard of care chemoimmunotherapy PLUS early intervention of UF-KURE19.(Up to 12 months after treatment)