ClinicalTrials.gov record NCT04545762

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

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 17, 2026

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

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 1An early-stage study, usually small, mainly to check safety, side effects and how much of a treatment can be given. Whether it works is not the main question yet.
Age18 years old and older
SexAll
LocationUnited States
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This open‑label phase 1 study evaluates anti‑CD19 CAR‑T cells in adults with relapsed or refractory CD19+ B‑cell non‑Hodgkin lymphomas. Participants undergo blood cell collection for CAR‑T manufacturing, short lymphodepleting chemotherapy, and a single CAR‑T infusion, then are followed for 12 months with longer-term survival follow-up up to 15 years. The trial includes a dose‑expansion phase (the dose‑escalation phase is closed to enrollment).

What it is studying. The study is testing the safety of autologous anti‑CD19 CAR‑T cell infusion and aims to determine the recommended dose for phase 2. It also evaluates the toxicity related to cell collection and infusion, describes tumor response, and assesses whether local manufacturing can reliably produce the CAR‑T product.

What the researchers hope to learn. Primary goals: evaluate safety of anti‑CD19 CAR‑T infusion and determine the recommended phase 2 dose (RP2D). Secondary goals: assess safety/toxicity of collection and infusion, describe anti‑tumor responses (response rates and duration), evaluate feasibility of local CAR‑T cell manufacturing, and collect progression‑free and overall survival data.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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).

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Fludarabine
  • Cyclophosphamide
Biological
  • anti-CD19 CAR-T cells

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • THE DOSE ESCALATION COHORT IS CLOSED TO FURTHER ENROLLMENT.
  • Dose expansion Cohorts:
  • Cohort B (Burkitt):
  • 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.
  • 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"
  • Cohort M/W (Marginal/Waldenström):
  • Participants must have a diagnosis of relapsed or refractory Marginal Zone Lymphoma (MZL), or Lymphoplasmacytic Lymphoma (LPL)/Waldenström Macroglobulinemia (WM):
  • o Participants with indolent lymphomas (nodal or extranodal marginal zone lymphoma, and lymphoplasmacytic lymphoma) must have relapsed after or have been refractory to ≥ 2 prior lines of multi-agent chemoimmunotherapy including prior exposure to an anti-CD20 antibody and an alkylating agent.
  • Participants must have measurable disease as defined below:
  • o Participants with Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia: must either have PET-positive disease according to "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification" or serum monoclonal immunoglobulin M (IgM) paraprotein > 0.5 g/dL.
  • Participants with indolent lymphoma (Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia) must have symptomatic disease or steady progression necessitating systemic treatment per investigator discretion.
  • In addition, all participants must meet the following criteria:
  • 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.
  • Age ≥18 years at the time of consent.
  • Absolute lymphocyte count > 100/UL.
  • Eastern Cooperative Oncology Group (ECOG) performance status < 2.
  • Adequate organ function, defined as:
  • Adequate bone marrow function for apheresis and lymphodepleting chemotherapy
  • Hemoglobin >8 gm/dl (transfusions allowed)
  • Platelets >50,000/uL (transfusions allowed)
  • Absolute Neutrophil Count (ANC) > 500/uL
  • 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
  • Serum Creatinine < 2 x the institutional ULN
  • 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.
  • Adequate vascular access for leukapheresis procedure (either peripheral line or surgically placed line).
  • 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.
  • Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method.
  • Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion criteria

  • Autologous transplant within 6 weeks of planned CAR-T cell infusion.
  • Recipient of prior CAR-T cell therapy targeting CD19 outside of this protocol.
  • Active other malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, or breast).
  • Human immunodeficiency virus (HIV) seropositivity.
  • 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.)
  • 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.
  • 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.
  • 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.
  • History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months.
  • Body weight <40 kilograms(kg).
  • Eligibility for Infusion of Investigational Product:
  • Participants will undergo an evaluation of eligibility on day 1 prior to infusion of anti-CD19 CAR-T cell product. This eligibility criterion will include the inclusion and exclusion criteria required for enrollment with the following exceptions and additions:
  • 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.
  • ECOG performance status < 2
  • 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.
  • No new neurologic symptoms suggestive of an active central nervous system condition, or uncontrolled CNS involvement by lymphoma.
  • No corticosteroid use within 7 days prior to infusion (with exception of agents used for prevention of emesis during lymphodepletive chemotherapy).

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

This is an open-label, pilot, phase 1 study to determine the safety profile of anti-CD19 CAR-T cell infusion in participants with R/R B-cell NHL. PRIMARY OBJECTIVES

  • To evaluate the safety of administering chimeric antigen receptor T cells targeting CD-19 to patients with relapsed or refractory CD19+ B-cell non-Hodgkin lymphoma (NHL).
  • To determine the recommended phase 2 dose (RP2D) for this cellular therapy.

SECONDARY OBJECTIVES

  • To assess the safety and toxicity of cell collection and infusion of CAR-T cells targeting CD19 in patients with relapsed or refractory CD19+ B cell NHL.
  • To describe the efficacy of chimeric antigen receptor T cells targeting CD-19 in patients with relapsed or refractory CD19+ B cell NHL.
  • To evaluate the feasibility of CD19 CAR T cell manufacturing for patients with relapsed or refractory CD19+ B cell NHL of local manufacturing and ability to produce adequate quantities of vector positive T-cells.

OUTLINE Participants will be enrolled to either the dose escalation or dose expansion cohorts. Dose Escalation: CLOSED TO ENROLLMENT Dose Expansion: The dose expansion phase of the study will be limited to two disease-specific cohorts:

  • Cohort B: Participants with Burkitt lymphoma (B).
  • Cohort M/W: Participants with Marginal Zone Lymphoma (MZL) and Waldenström Macroglobulinemia (WM).

Participants will receive an infusion of Anti-CD19 CAR-T cells during the main study and will be followed for 12 months before being transferred into long term follow-up during years 1 to 15.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

After screening to confirm CD19 positivity and eligibility, participants undergo apheresis (one day) to collect their T cells. The collected cells are sent for CAR‑T manufacturing (about 13–14 days) while participants receive lymphodepleting chemotherapy (IV cyclophosphamide and fludarabine). Participants then receive a single infusion of anti‑CD19 CAR‑T cells (given over about 5–30 minutes) and are closely monitored with blood tests and scans. Follow‑up includes visits for about 12 months after infusion and long‑term survival follow‑up extending up to 15 years; a pre‑infusion eligibility check (no recent corticosteroids within 7 days, no new neurologic symptoms, acceptable labs) is done the day of infusion. The study tracks, for each participant, whether the CAR‑T therapy is successfully manufactured and meets its required release criteria.

How the study is structured. An interventional, non‑randomized, open‑label phase 1 trial with a sequential design. Apheresis collects a participant's lymphocytes, CAR‑T cells are manufactured (about 13–14 days), participants receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine), then a single CAR‑T infusion. The dose‑escalation portion is closed; current enrollment is in disease‑specific dose‑expansion cohorts. Follow‑up visits occur through 12 months, with long‑term survival follow‑up up to 15 years.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
  • The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on Waldenström macroglobulinemia

Clinical trials63 trials listed for Waldenström macroglobulinemiaEvery trial the registry lists for Waldenström macroglobulinemia, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in Waldenström macroglobulinemia researchLatest monthly update: September 2026. Includes: Upfront treatment outcomes. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Sep 11, 2020
Primary completion
Oct 31, 2026 (estimated)
Study completion
Oct 31, 2026 (estimated)
Target enrollment
36 participants (estimated)
Last updated on registry
Jun 22, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
C. Babis Andreadis
Collaborators
  • University of California, Davis

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

Terms used on this page · explanations by MedicalUpdates.ai

chimeric antigen receptor
A treatment in which a person's own immune cells (T cells) are collected, modified in a laboratory to recognise a target, and returned to the body.
DOSE ESCALATION
Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
COHORT
A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
ENROLLMENT
The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
relapsed or refractory
A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
relapsed
A condition that improved with treatment and has since returned or worsened.
upper limit of normal
The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
Positron Emission Tomography
A scan in which a small amount of a radioactive tracer is injected so that activity in tissues can be seen. Often combined with a CT or MRI scan.
prior lines
Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
biopsy
Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
ECOG
A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
Absolute Neutrophil Count
The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
echocardiogram
An ultrasound scan of the heart. A transesophageal echocardiogram is done through a probe passed into the food pipe for a closer view.
Women of childbearing potential
Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
written informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
adverse events
Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.
immunosuppressive
A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
Investigational Product
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
exclusion criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
principal investigator
The doctor or scientist responsible for running the study at a site or overall.
corticosteroid
Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
open-label
No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
recommended phase 2 dose
The dose chosen at the end of a phase 1 study for testing in later studies, based on safety and other measurements.
long term follow-up
Observation that continues for years after the study treatment, often required for gene and cell therapies.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

← Back to clinical trials