RECRUITING

Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma

Conditions

Refractory Non-Hodgkin Lymphoma Burkitt Lymphoma Mantle Cell Lymphoma Follicular Lymphoma Lymphoplasmacytic Lymphoma Primary Mediastinal Large B Cell Lymphoma Diffuse Large B Cell Lymphoma Small Lymphocytic Lymphoma Transformed Lymphoma Non-Hodgkin Lymphoma CAR-T Therapy

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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 will assess safety and feasibility of infusing genetically modified autologous T cells transduced to express a chimeric antigen receptor targeting the B cell surface antigen Cluster of Differentiation 19 (CD19).

Official Title

A Phase 1 Clinical Trial of Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma

Quick Facts

Study Start:2020-09-11

Study Completion:2026-10-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04545762

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
1. Participants must have a diagnosis of relapsed or refractory Burkitt Lymphoma * Participants with Burkitt lymphoma must have relapsed or failed to respond to at least 1 prior line of multiagent chemoimmunotherapy with prior exposure to both an anti-CD20 antibody agent and an anthracycline. * No significant circulating disease, defined as an elevated total lymphocyte count above the upper limit of normal (ULN) due to the presence of malignant cells. 2. Participants must have measurable disease as defined below: * Participants with Burkitt Lymphoma must have Positron Emission Tomography (PET)-positive disease according to "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification" 1. Participants must have a diagnosis of relapsed or refractory Marginal Zone Lymphoma (MZL), or Lymphoplasmacytic Lymphoma (LPL)/Waldenström Macroglobulinemia (WM): 2. Participants must have measurable disease as defined below: 3. Participants with indolent lymphoma (Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia) must have symptomatic disease necessitating systemic treatment. 1. CD19-positive by either immunohistochemistry or flow cytometry analysis on any biopsy. If prior anti-CD19 therapy has been administered, CD19-positivity has to be re-established on the most recent biopsy. 2. Age ≥18 years at the time of consent. 3. Absolute lymphocyte count \> 100/UL. 4. Eastern Cooperative Oncology Group (ECOG) performance status \< 2. 5. Adequate organ function, defined as: 1. Adequate bone marrow function for apheresis and lymphodepleting chemotherapy 2. Hemoglobin \>8 gm/dl (transfusions allowed) 3. Platelets \>50,000/uL (transfusions allowed) 4. Absolute Neutrophil Count (ANC) \> 500/uL 5. alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \< 3 x institutional upper limit of normal (ULN) and Total bilirubin \< 1.5 mg/dl x institutional ULN, except with Gilbert's syndrome 6. Serum Creatinine \< 2 x the institutional ULN 7. Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) \> 40% as assessed by echocardiogram or multiple uptake gated acquisition (MUGA) within 3 months of screening. Repeat testing may occur at Investigator's discretion. 6. Adequate vascular access for leukapheresis procedure (either peripheral line or surgically placed line). 7. Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must have a negative serum or urine pregnancy test AND agree to use highly effective methods of contraception for 1 year after the last dose of anti-CD19 CAR-T cells. 8. Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method. 9. Ability to understand a written informed consent document, and the willingness to sign it.	1. Autologous transplant within 6 weeks of planned CAR-T cell infusion. 2. Recipient of prior CAR-T cell therapy targeting CD19 outside of this protocol. 3. Active other malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, or breast). 4. Human immunodeficiency virus (HIV) seropositivity. 5. Serologic status reflecting active hepatitis B or C infection. Participants 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 participants will be excluded.) 6. Participants 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. 7. 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. 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. NOTE: Women of childbearing potential must have a negative serum or urine pregnancy test. 8. Participants with history of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease. 9. History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months. 10. Body weight \<40 kilograms(kg). 1. No significant laboratory abnormalities. Laboratory result abnormalities that are considered not clinically significant by the principal investigator AND are not the result of a demonstrated active infection or an active central nervous system condition. 2. ECOG performance status \< 2 3. No evidence of uncontrolled intercurrent illness including, but not limited to ongoing or active infection, inflammatory response, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations. 4. No new neurologic symptoms suggestive of an active central nervous system condition, or uncontrolled CNS involvement by lymphoma. 5. No corticosteroid use within 7 days prior to infusion (with exception of agents used for prevention of emesis during lymphodepletive chemotherapy).

Inclusion Criteria

Exclusion Criteria

1. Participants must have a diagnosis of relapsed or refractory Burkitt Lymphoma
* Participants with Burkitt lymphoma must have relapsed or failed to respond to at least 1 prior line of multiagent chemoimmunotherapy with prior exposure to both an anti-CD20 antibody agent and an anthracycline.
* No significant circulating disease, defined as an elevated total lymphocyte count above the upper limit of normal (ULN) due to the presence of malignant cells.
2. Participants must have measurable disease as defined below:
* Participants with Burkitt Lymphoma must have Positron Emission Tomography (PET)-positive disease according to "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification"
1. Participants must have a diagnosis of relapsed or refractory Marginal Zone Lymphoma (MZL), or Lymphoplasmacytic Lymphoma (LPL)/Waldenström Macroglobulinemia (WM):
2. Participants must have measurable disease as defined below:
3. Participants with indolent lymphoma (Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia) must have symptomatic disease necessitating systemic treatment.
1. CD19-positive by either immunohistochemistry or flow cytometry analysis on any biopsy. If prior anti-CD19 therapy has been administered, CD19-positivity has to be re-established on the most recent biopsy.
2. Age ≥18 years at the time of consent.
3. Absolute lymphocyte count \> 100/UL.
4. Eastern Cooperative Oncology Group (ECOG) performance status \< 2.
5. Adequate organ function, defined as:
1. Adequate bone marrow function for apheresis and lymphodepleting chemotherapy
2. Hemoglobin \>8 gm/dl (transfusions allowed)
3. Platelets \>50,000/uL (transfusions allowed)
4. Absolute Neutrophil Count (ANC) \> 500/uL
5. alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \< 3 x institutional upper limit of normal (ULN) and Total bilirubin \< 1.5 mg/dl x institutional ULN, except with Gilbert's syndrome
6. Serum Creatinine \< 2 x the institutional ULN
7. Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) \> 40% as assessed by echocardiogram or multiple uptake gated acquisition (MUGA) within 3 months of screening. Repeat testing may occur at Investigator's discretion.
6. Adequate vascular access for leukapheresis procedure (either peripheral line or surgically placed line).
7. Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must have a negative serum or urine pregnancy test AND agree to use highly effective methods of contraception for 1 year after the last dose of anti-CD19 CAR-T cells.
8. Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method.
9. Ability to understand a written informed consent document, and the willingness to sign it.

1. Autologous transplant within 6 weeks of planned CAR-T cell infusion.
2. Recipient of prior CAR-T cell therapy targeting CD19 outside of this protocol.
3. Active other malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, or breast).
4. Human immunodeficiency virus (HIV) seropositivity.
5. Serologic status reflecting active hepatitis B or C infection. Participants 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 participants will be excluded.)
6. Participants 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.
7. 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. 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. NOTE: Women of childbearing potential must have a negative serum or urine pregnancy test.
8. Participants with history of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.
9. History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months.
10. Body weight \<40 kilograms(kg).
1. No significant laboratory abnormalities. Laboratory result abnormalities that are considered not clinically significant by the principal investigator AND are not the result of a demonstrated active infection or an active central nervous system condition.
2. ECOG performance status \< 2
3. No evidence of uncontrolled intercurrent illness including, but not limited to ongoing or active infection, inflammatory response, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations.
4. No new neurologic symptoms suggestive of an active central nervous system condition, or uncontrolled CNS involvement by lymphoma.
5. No corticosteroid use within 7 days prior to infusion (with exception of agents used for prevention of emesis during lymphodepletive chemotherapy).

Contacts and Locations

Study Contact

UCSF HDFCCC Cancer Immunotherapy Program

CONTACT

877-827-3222

HDFCCC.CIP@ucsf.edu

Principal Investigator

C. Babis Andreadis, MD

PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Study Locations (Sites)

University of California, San Francisco

San Francisco, California, 94143

United States

Collaborators and Investigators

Sponsor: C. Babis Andreadis

C. Babis Andreadis, MD, PRINCIPAL_INVESTIGATOR, University of California, San Francisco

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 Date2020-09-11

Study Completion Date2026-10-31

Study Record Updates

Study Start Date2020-09-11

Study Completion Date2026-10-31

Terms related to this study

Keywords Provided by Researchers

CAR-T Therapy

Additional Relevant MeSH Terms

Refractory Non-Hodgkin Lymphoma
Burkitt Lymphoma
Mantle Cell Lymphoma
Follicular Lymphoma
Lymphoplasmacytic Lymphoma
Primary Mediastinal Large B Cell Lymphoma
Diffuse Large B Cell Lymphoma
Small Lymphocytic Lymphoma
Transformed Lymphoma
Non-Hodgkin Lymphoma