The goal of this Phase II single-arm, open-label clinical trial is to evaluate whether UF-KURE19, an autologous CD19-directed CAR-T cell therapy manufactured t…The goal of this Phase II single-arm, open-label clinical trial is to evaluate whether UF-KURE19, an autologous CD19-directed CAR-T cell therapy manufactured through an ultra-fast (less than 1 day) process, can treat adult patients (18 years and older, male or female) with relapsed or refractory B-cell Non-Hodgkin Lymphoma (NHL), including Large B-Cell Lymphoma (LBCL), Follicular Lymphoma (FL), and Marginal Zone Lymphoma (MZL).
The participants will be divided in two cohorts:
81 participants in Cohort 1: Large B-Cell Lymphoma (LBCL) 24 participants in Cohort 2: Follicular Lymphoma (FC) and Marginal Zone Lymphoma (MZL)
The main questions it aims to answer are:
There is no comparison group. This is a single-arm study, (all participants receive UF-KURE19) with 2 cohorts as outlined above.
Participants will:
Inclusion Criteria:
Male or female patients aged 18 years or older.
Participants must have histologically confirmed, CD19 positive (by IHC or flow cytometry) NHL at the most recent biopsy. If a previous CD19 targeting therapy was utilized, a biopsy should be available after this therapy demonstrating sustained CD19 expression.
Subjects in cohort 1 (LBCL) must meet the following inclusion criteria:
a. Subjects must fit one of the following diagnoses: i. Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma) ii. High-grade B-cell lymphoma iii. Primary mediastinal large B-cell lymphoma iv. Follicular lymphoma grade 3B b. LBCL disease status must consist of one of the following: i. Relapsed after 2 or more lines of chemoimmunotherapy OR ii. Disease that is refractory to first line chemoimmunotherapy or relapses within 12 months of completion of initial chemoimmunotherapy OR iii. Relapsed disease that is ineligible to receive hematopoietic stem cell transplantation due to comorbidities or age or patient preference
Subjects in cohort 2 (FL) must meet the following inclusion criteria:
a. Subjects must fit one of the following diagnoses: i. Follicular lymphoma ii. Marginal zone lymphoma b. Disease status must have relapsed after 2 or more lines of therapy
ECOG Performance status ≤ 2.
Participants must exhibit measurable disease with at least one FDG avid lesion at enrollment per Lugano Criteria
Minimum of 2 weeks since prior radiation therapy or systemic therapy to treat malignancy at the time of leukapheresis.
Total bilirubin ≤ 1.5X institutional upper limit of normal.
AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal.
Calculated creatinine clearance ≥ 30mL/min estimated by the Cockcroft - Gault formula.
Cardiac ejection fraction of ≥ 45%.
Adequate pulmonary function, defined as ≤ Grade 1 dyspnea (unless considered secondary to lymphoma) and oxygen saturation (SaO2) ≥ 90% on room air.
Subjects (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document.
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 90 days after the UF-KURE19 CAR-T cell infusion.
A woman is considered to be of childbearing potential if she is post menarcheal, has not reached a postmenopausal state (< 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the UF-KURE19 CAR-T cell infusion. Men must refrain from donating sperm during this same period. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the UF-KURE19 CAR-T cell infusion to avoid potential embryonal or fetal exposure. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
Inclusion of Women and Minorities: Men, women and members of all races and ethnic groups are eligible for this trial.
Exclusion Criteria:
Inclusion Criteria
Male or female patients aged 18 years or older.
Participants must have histologically confirmed, CD19 positive (by IHC or flow cytometry) NHL at the most recent biopsy. If a previous CD19 targeting therapy was utilized, a biopsy should be available after this therapy demonstrating sustained CD19 expression.
Subjects in cohort 1 (LBCL) must meet the following inclusion criteria:
a. Subjects must fit one of the following diagnoses: i. Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma) ii. High-grade B-cell lymphoma iii. Primary mediastinal large B-cell lymphoma iv. Follicular lymphoma grade 3B b. LBCL disease status must consist of one of the following: i. Relapsed after 2 or more lines of chemoimmunotherapy OR ii. Disease that is refractory to first line chemoimmunotherapy or relapses within 12 months of completion of initial chemoimmunotherapy OR iii. Relapsed disease that is ineligible to receive hematopoietic stem cell transplantation due to comorbidities or age or patient preference
Subjects in cohort 2 (FL) must meet the following inclusion criteria:
a. Subjects must fit one of the following diagnoses: i. Follicular lymphoma ii. Marginal zone lymphoma b. Disease status must have relapsed after 2 or more lines of therapy
ECOG Performance status ≤ 2.
Participants must exhibit measurable disease with at least one FDG avid lesion at enrollment per Lugano Criteria
Minimum of 2 weeks since prior radiation therapy or systemic therapy to treat malignancy at the time of leukapheresis.
Total bilirubin ≤ 1.5X institutional upper limit of normal.
AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal.
Calculated creatinine clearance ≥ 30mL/min estimated by the Cockcroft - Gault formula.
Cardiac ejection fraction of ≥ 45%.
Adequate pulmonary function, defined as ≤ Grade 1 dyspnea (unless considered secondary to lymphoma) and oxygen saturation (SaO2) ≥ 90% on room air.
Subjects (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document.
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for at least 90 days after the UF-KURE19 CAR-T cell infusion.
A woman is considered to be of childbearing potential if she is post menarcheal, has not reached a postmenopausal state (< 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the UF-KURE19 CAR-T cell infusion. Men must refrain from donating sperm during this same period. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the UF-KURE19 CAR-T cell infusion to avoid potential embryonal or fetal exposure. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
Inclusion of Women and Minorities: Men, women and members of all races and ethnic groups are eligible for this trial.
Exclusion Criteria
daniel@cellserveglobal.net7343539036
This Cohort will include patients with Diffuse Large B-cell lymphoma (DLBCL)
This cohort will include patients with: Follicular Lymphoma (FC) and Marginal Zone Lymphoma (MZL)
olaselkadi@gmail.com647-865-0773
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