ACTIVE_NOT_RECRUITING

Evaluate the Safety of UF-KURE19 Cells in Non-Hodgkin Lymphomas

Conditions

Non Hodgkin Lymphoma UF-KURE19 CD19 CAR-T cells

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 1/1b Multicenter, Open Label Study to Evaluate the Safety of UF-KURE19 Cells in Patients With B Cell Non-Hodgkin Lymphomas

Quick Facts

Study Start:2023-04-26

Study Completion:2026-04-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05400109

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 ≤ 2. * 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. * 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%, and no more than trivial (or trace, minimal or mild) pericardial effusion, as determined by an echocardiogram. * Adequate pulmonary function, defined as ≤ Grade 1 dyspnea (unless considered secondary to lymphoma) and oxygen saturation (SaO2) ≥ 92% on room air. If pulmonary function tests (PFTs) are performed based on the clinical judgment of the treating physician, patients with forced expiratory volume in 1 second (FEV1) * Participants (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 postmenarcheal, 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. * 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.	* 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. * Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded). * Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease. * Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements. * History of active autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of systemic immunosuppressive medications other than low dose steroids \[i.e. maximum of 15mg prednisone equivalent\] within the last 6 months. * Circulating malignant B cells in peripheral blood detected by complete blood count at the time of subject enrollment.

Inclusion Criteria

Exclusion 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 ≤ 2.
* 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.
* 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%, and no more than trivial (or trace, minimal or mild) pericardial effusion, as determined by an echocardiogram.
* Adequate pulmonary function, defined as ≤ Grade 1 dyspnea (unless considered secondary to lymphoma) and oxygen saturation (SaO2) ≥ 92% on room air. If pulmonary function tests (PFTs) are performed based on the clinical judgment of the treating physician, patients with forced expiratory volume in 1 second (FEV1)
* Participants (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 postmenarcheal, 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.
* 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.

* 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.
* Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded).
* Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.
* Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
* History of active autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of systemic immunosuppressive medications other than low dose steroids \[i.e. maximum of 15mg prednisone equivalent\] within the last 6 months.
* Circulating malignant B cells in peripheral blood detected by complete blood count at the time of subject enrollment.

Contacts and Locations

Principal Investigator

Changchun Deng, MD, PhD

PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Study Locations (Sites)

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242

United States

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106

United States

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195

United States

Collaborators and Investigators

Sponsor: David Wald

Changchun Deng, MD, PhD, PRINCIPAL_INVESTIGATOR, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-04-26

Study Completion Date2026-04-01

Study Record Updates

Study Start Date2023-04-26

Study Completion Date2026-04-01

Terms related to this study

Keywords Provided by Researchers

UF-KURE19
CD19 CAR-T cells
Non Hodgkin Lymphoma

Additional Relevant MeSH Terms

Non Hodgkin Lymphoma