Refractory Non-Hodgkin LymphomaPhase 1NCT04545762
Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
A Phase 1 study testing Fludarabine, Cyclophosphamide and anti-CD19 CAR-T cells in people with Refractory Non-Hodgkin Lymphoma and Burkitt Lymphoma, run by C. Babis Andreadis at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Non-Hodgkin Lymphoma, Burkitt Lymphoma, Mantle Cell Lymphoma
- What is being tested?
- Fludarabine, Cyclophosphamide and anti-CD19 CAR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Sep 2020to 31 Oct 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Dose expansion Cohorts:
- Cohort B (Burkitt):
- Participants must have a diagnosis of relapsed or refractory Burkitt Lymphoma o 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.
- o 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"
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- 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:
- 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:
- o 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
- o Serum Creatinine < 2 x the institutional ULN
- o 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 bone marrow function for apheresis and lymphodepleting chemotherapy
- Adequate hematologic function, defined as:
- Hemoglobin >8 gm/dl (transfusions allowed)
- Platelets >50,000/uL (transfusions allowed)
- Absolute Neutrophil Count (ANC) > 500/uL
- Note: These criteria must be met and documented at least once during the screening period. Participants are not required to continue to meet these laboratory thresholds through initiation of study treatment. If a laboratory value subsequently falls below the specified threshold due to a transient or reversible clinical circumstance, the Principal Investigator may determine that the participant remains eligible, based on clinical assessment of the participant's underlying hematologic function and the safety of proceeding with study treatment.
- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
UCSF HDFCCC Cancer Immunotherapy Program, 877-827-3222, HDFCCC.CIP@ucsf.edu
cancertrials@ucsf.edu
About this study
Official title: A Phase 1 Clinical Trial of Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
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).
Read the detailed description
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.
- Conditions
- Refractory Non-Hodgkin Lymphoma, Burkitt Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Primary Mediastinal Large B Cell Lymphoma
- Being tested
- Fludarabine, Cyclophosphamide, anti-CD19 CAR-T cells
- Keywords
- CAR-T Therapy
- Medical subject headings
- Lymphoma, Non-Hodgkin, Burkitt Lymphoma, Lymphoma, Mantle-Cell, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Large B-Cell, Diffuse, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Also called Fludarabine 30mg/m2, Fludara
Given intravenously (IV)
CyclophosphamideDrug
Also called Cyclophosphamide 300mg/m2, Cytoxan, Endoxan, Neosar
Given intravenously (IV)
anti-CD19 CAR-T cellsBiological
Also called CD19-directed Chimeric Antigen Receptor T-Cell (CAR T-cell) therapy, CD19-directed chimeric antigen receptor (CAR) T-cell therapy
Single infusion
| Study group | Role | What they receive |
|---|---|---|
| CLOSED TO ENROLLMENT: Dose escalation (CART-T Therapy) | Experimental | Participants will undergo Apheresis (1 day) to collect autologous lymphocytes/ mononuclear cells as per University of California, San Francisco (UCSF) institutional practices. CAR-T cell manufacturing (estimated ~13-14 days), during which participants will receive a lymphodepleting regimen of immunosuppressive chemotherapy (Cyclophosphamide 300 mg/m2/IV and fludarabine 30 mg/m2 /IV) followed by the infusion of CAR-T cells at an initial dose of 5 x 10^5 cells/kg, targeting CD19 over 5-30 minutes. Participants will be followed up 30 days after infusion, for up to 12 months, if the participant in continued remission, and for survival up to 15 years. |
| Dose Expansion: Burkitt, Marginal Zone, or Waldenström Macroglobulinemia ONLY (CAR-T Therapy) | Experimental | Participants with Burkitt lymphoma, or Marginal Zone Lymphoma (MZL) and Waldenström Macroglobulinemia (WM) will undergo Apheresis (1 day) to collect autologous lymphocytes/ mononuclear cells as per University of California, San Francisco (UCSF) institutional practices. CAR-T cell manufacturing (estimated ~13-14 days), during which participants will receive a lymphodepleting regimen of immunosuppressive chemotherapy (Cyclophosphamide 300 mg/m2/IV and fludarabine 30 mg/m2 /IV) followed by the infusion of the maximum tolerated dose of CAR-T cells established in the dose escalation phase, targeting CD19 over 5-30 minutes. Participants will be followed up 30 days after infusion, for up to 12 months, if the participant in continued remission, and for survival up to 15 years. Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: anti-CD19 CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with treatment-emergent adverse events (AEs)
Participants treated with conforming product who received the target doses of anti-CD19 CAR-T infusion will be included in the analysis. Proportion of participants with treatment-emergent adverse events of CAR-T in B-cell NHL, as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0), revised Cytokine Release Syndrome (CRS) grading criteria, and American Society for Transplantation and Cellular Therapy (ASTCT) immune effector cell (IEC) -associated neurotoxicity syndrome (ICANS) Consensus Grading for Adults (for neurotoxicity grading).
Measured: From initiation of study treatment to 12 months following CAR-T infusion, approximately 15 months
Proportion of participants who experience a dose-limiting toxicity (DLT) (Dose escalation)
A DLT includes AEs graded according to CTCAE version 5.0, with the exceptions of CRS and neurotoxicity, which are graded using CRS and ICANS criteria. DLTs must 1) be suspected to be secondary to CAR-T cell infusion, 2) occur during the first 30 days after infusion and 3) meet the following criteria: 1. Grade 3 or 4 non-hematologic toxicities of any duration, with following exceptions: Grade 3 laboratory abnormalities without associated symptomatology or clinical consequence that resolve in < 7 days; AEs associated with Grade <= 2 CRS; Toxicities associated with Grade 3 CRS (except cardiac or pulmonary organ toxicity) that improves to grade <= 2 within 3 days of intervention; isolated renal or hepatic grade 3 organ toxicity that does not resolve within 7 days; Laboratory abnormalities compatible with tumor lysis syndrome; Grade 4 hematological toxicity that persists at grade >= 3 despite maximum supportive care for >21 days.
Measured: From initiation of study treatment to 30 days following CAR-T infusion
Secondary outcomes (10)
Proportion of participants with CAR-T infusion related adverse events (Dose Escalation)
The proportion of participants with adverse events related to the collection and infusion of CAR-T cells targeting CD19 will be reported.
Measured: From initiation of CD19 CAR T-cell manufacturing to end of infusion, approximately 18 days
Proportion of participants with delayed infusion due to study-related adverse events
The proportion of participants who have their infusion delayed due to and AE will be reported.
Measured: From T-cell collection to end of infusion, approximately 18 days
Overall Response Rate (ORR)
Overall response rates will be reported as proportions of participants by arm. The 2014 Lugano Response for Malignant Lymphoma criteria will be to determine response: Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Relapse and Progression (PD). For the Waldenstrom's Macroglobulinemia cohort, the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) response criteria will be used to determine response: CR, very good partial response (VGPR), PR, minor response (MR), SD, and PD.
Measured: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
Complete Response Rate
Complete response rates will be reported as will be reported as proportions of participants by arm.
Measured: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
Partial Response Rate
Partial response rates will be reported as will be reported as proportions of participants by arm.
Measured: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
Median duration of response
For participants who have been documented to be responders under the 2014 Lugano criteria or the IWWM-11 criteria, and defined as the median time from the documented beginning of response (CR or PR) to the time of relapse.
Measured: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
Median Progression-free Survival (PFS)
PFS is defined as the median time from entry onto study until a diagnosis of lymphoma progression or death from any cause at 12 months after receiving CAR-T infusion.
Measured: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
Median Overall Survival
Defined as the median time from entry onto study until death from any cause
Measured: Up to 15 years
Proportion of participants for whom CD19 CAR T-cell therapy is manufactured
The proportion of participants for whom CD19 CAR T-cell therapy is adequately manufactured and meets pre-specified release criteria.
Measured: From initiation of CD19 CAR T-cell manufacturing to end of infusion, approximately 18 days
Proportion of participants who complete study treatment
Feasibility will be assessed by the proportion of participants who are able to complete the study regimen and receive infusion of CAR-T therapy.
Measured: From initiation of CD19 CAR T-cell manufacturing to end of infusion, approximately 18 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2020
- Study start11 Sep 2020
- Primary completion31 Oct 2026 (estimated)
- Study completion31 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Refractory Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- C. Babis Andreadis
- Sponsor type
- University, hospital or other
- Collaborators
- University of California, Davis
- Responsible party
- Sponsor-investigator, C. Babis Andreadis, University of California, San Francisco
- Investigators
- Carrie Ho, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04545762
- Sponsor's protocol ID
- 19703
- Other IDs
- NCI-2020-06711
- Status last verified
- Oct 2026
- First submitted
- 31 Aug 2020
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PubMed 34515338
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Clinical Trial of Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT04545762
- Acronym / sponsor ID
- 19703
- Conditions
- Refractory Non-Hodgkin Lymphoma, Burkitt Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Primary Mediastinal Large B Cell Lymphoma
- Keywords
- CAR-T Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- C. Babis AndreadisUniversity, hospital or other
- Collaborators
- University of California, Davis
- Study start
- 11 Sep 2020 (actual)
- Primary completion
- 31 Oct 2026 (estimated)
- Study completion
- 31 Oct 2026 (estimated)
- First posted
- 11 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CLOSED TO ENROLLMENT: Dose escalation (CART-T Therapy) | Experimental | –Participants will undergo Apheresis (1 day) to collect autologous lymphocytes/ mononuclear cells as per University of California, San Francisco (UCSF) institutional practices. CAR-T cell manufacturing (estimated ~13-14 days), during which participants will receive a lymphodepleting regimen of immunosuppressive chemotherapy (Cyclophosphamide 300 mg/m2/IV and fludarabine 30 mg/m2 /IV) followed by the infusion of CAR-T cells at an initial dose of 5 x 10^5 cells/kg, targeting CD19 over 5-30 minutes. Participants will be followed up 30 days after infusion, for up to 12 months, if the participant in continued remission, and for survival up to 15 years. |
| Dose Expansion: Burkitt, Marginal Zone, or Waldenström Macroglobulinemia ONLY (CAR-T Therapy) | Experimental | Drug: Fludarabine, Drug: Cyclophosphamide, Biological: anti-CD19 CAR-T cellsParticipants with Burkitt lymphoma, or Marginal Zone Lymphoma (MZL) and Waldenström Macroglobulinemia (WM) will undergo Apheresis (1 day) to collect autologous lymphocytes/ mononuclear cells as per University of California, San Francisco (UCSF) institutional practices. CAR-T cell manufacturing (estimated ~13-14 days), during which participants will receive a lymphodepleting regimen of immunosuppressive chemotherapy (Cyclophosphamide 300 mg/m2/IV and fludarabine 30 mg/m2 /IV) followed by the infusion of the maximum tolerated dose of CAR-T cells established in the dose escalation phase, targeting CD19 over 5-30 minutes. Participants will be followed up 30 days after infusion, for up to 12 months, if the participant in continued remission, and for survival up to 15 years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Participants must have a diagnosis of relapsed or refractory Burkitt Lymphoma o 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.
- o 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 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.
Key exclusion criteria (17 listed)
- 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.)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FludarabineAlso: Fludarabine 30mg/m2, FludaraGiven intravenously (IV) | Drug | Dose Expansion: Burkitt, Marginal Zone, or Waldenström Macroglobulinemia ONLY (CAR-T Therapy) |
| CyclophosphamideAlso: Cyclophosphamide 300mg/m2, Cytoxan, Endoxan, NeosarGiven intravenously (IV) | Drug | Dose Expansion: Burkitt, Marginal Zone, or Waldenström Macroglobulinemia ONLY (CAR-T Therapy) |
| anti-CD19 CAR-T cellsAlso: CD19-directed Chimeric Antigen Receptor T-Cell (CAR T-cell) therapy, CD19-directed chimeric antigen receptor (CAR) T-cell therapySingle infusion | Biological | Dose Expansion: Burkitt, Marginal Zone, or Waldenström Macroglobulinemia ONLY (CAR-T Therapy) |
Primary outcome
Proportion of participants with treatment-emergent adverse events (AEs)
Time frame: From initiation of study treatment to 12 months following CAR-T infusion, approximately 15 months
Participants treated with conforming product who received the target doses of anti-CD19 CAR-T infusion will be included in the analysis. Proportion of participants with treatment-emergent adverse events of CAR-T in B-cell NHL, as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0), revised Cytokine Release Syndrome (CRS) grading criteria, and American Society for Transplantation and Cellular Therapy (ASTCT) immune effector cell (IEC) -associated neurotoxicity syndrome (ICANS) Consensus Grading for Adults (for neurotoxicity grading).
Proportion of participants who experience a dose-limiting toxicity (DLT) (Dose escalation)
Time frame: From initiation of study treatment to 30 days following CAR-T infusion
A DLT includes AEs graded according to CTCAE version 5.0, with the exceptions of CRS and neurotoxicity, which are graded using CRS and ICANS criteria. DLTs must 1) be suspected to be secondary to CAR-T cell infusion, 2) occur during the first 30 days after infusion and 3) meet the following criteria: 1. Grade 3 or 4 non-hematologic toxicities of any duration, with following exceptions: Grade 3 laboratory abnormalities without associated symptomatology or clinical consequence that resolve in < 7 days; AEs associated with Grade <= 2 CRS; Toxicities associated with Grade 3 CRS (except cardiac or pulmonary organ toxicity) that improves to grade <= 2 within 3 days of intervention; isolated renal or hepatic grade 3 organ toxicity that does not resolve within 7 days; Laboratory abnormalities compatible with tumor lysis syndrome; Grade 4 hematological toxicity that persists at grade >= 3 despite maximum supportive care for >21 days.
10 secondary outcomes
Proportion of participants with CAR-T infusion related adverse events (Dose Escalation)
Time frame: From initiation of CD19 CAR T-cell manufacturing to end of infusion, approximately 18 days
Proportion of participants with delayed infusion due to study-related adverse events
Time frame: From T-cell collection to end of infusion, approximately 18 days
Overall Response Rate (ORR)
Time frame: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
Complete Response Rate
Time frame: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
Partial Response Rate
Time frame: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
Median duration of response
Time frame: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
Median Progression-free Survival (PFS)
Time frame: From initiation of study treatment to 12 months after getting CAR-T infusion, approximately 15 months
Median Overall Survival
Time frame: Up to 15 years
Proportion of participants for whom CD19 CAR T-cell therapy is manufactured
Time frame: From initiation of CD19 CAR T-cell manufacturing to end of infusion, approximately 18 days
Proportion of participants who complete study treatment
Time frame: From initiation of CD19 CAR T-cell manufacturing to end of infusion, approximately 18 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Derived from this study: PubMed 34515338Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
- Individual participant dataSharing planned: No
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B-ALL, DLBCL
Active, not recruitingPhase 2
Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
Relapsed/Refractory Peripheral T-Cell Lymphoma, Adult T Cell Leukemia/Lymphoma
RecruitingPhase 2
Testing the Effectiveness of a Combination Targeted Therapy (ViPOR) for Patients With Relapsed and/or Refractory Aggressive B-cell Lymphoma
High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements, Recurrent Diffuse Large B-Cell Lymphoma
RecruitingPhase 1/2
Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
Lymphoma, Waldenström Macroglobulinemia (WM)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Carrie Ho, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fludarabine, Cyclophosphamide and anti-CD19 CAR-T cells in people with Refractory Non-Hodgkin Lymphoma and Burkitt Lymphoma, run by C. Babis Andreadis at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact UCSF HDFCCC Cancer Immunotherapy Program (877-827-3222, HDFCCC.CIP@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with treatment-emergent adverse events (AEs) (time frame: From initiation of study treatment to 12 months following CAR-T infusion, approximately 15 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04545762, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.