Recurrent Diffuse Large B-Cell LymphomaPhase 1NCT05052528
Fludarabine and Cyclophosphamide With or Without Rituximab Before CD19 Chimeric Antigen Receptor T Cells for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma
A Phase 1 study testing Chimeric Antigen Receptor T-Cell Therapy, Cyclophosphamide and Fludarabine Phosphate in people with Recurrent Diffuse Large B-Cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, run by University of California, Davis at 1 site in United States.
Trial summary
This phase I trial evaluates the best dose, possible benefits and/or side effects of fludarabine and cyclophosphamide with or without rituximab before CD19 chimeric antigen receptor T cells in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or has not responded to previous treatment… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma
- What is being tested?
- Chimeric Antigen Receptor T-Cell Therapy, Cyclophosphamide and Fludarabine Phosphate
- 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
- 17 Sep 2021to 15 Dec 2027
- 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
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Commercial CD19 CAR T cell product not available for the patient
- Male or female, aged >= 18
- In good general health as evidenced by medical history or as determined by the principal investigator (PI)
- Ability to swallow oral medication and willingness to adhere to the study intervention and any required medications
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- For females of reproductive potential: use of highly effective contraception (oral contraceptives, intrauterine device) during screening confirmed with serum pregnancy test, and agreement to use such a method during study participation and for an additional 4 weeks after the end of CD19 CAR T cell infusion
- For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner
- Agreement to adhere to lifestyle considerations throughout study duration including abstaining from tobacco and drug use
- Subjects must have relapsed or refractory diffuse large B cell lymphoma treated with at least two lines of therapy Subjects must have failed to have a complete response, or have recurrent disease after the last treatment regimen. Subjects must have previously been treated with a regimen that includes an anthracycline and an anti-CD20 monoclonal antibody. Autologous transplant will be counted as one line of therapy
- (CNS cohort) SSubjects must have primary or secondary CNS lymphoma and must fail to achieve a complete response (refractory disease), have progressive disease, or relapsed disease per the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria following at least one prior line of therapy. First-line therapies include high dose methotrexate-based therapy but may also include temozolomide, high dose cytarabine,, lenalidomide, ibrutinib and rituximab. Radiation therapy, lenalidomide monotherapy and ibrutinib monotherapy are considered first line therapy if patient was not eligible for methotrexate-based chemotherapy at time of initial treatment but now meets study eligibility criteria
- The patient's disease must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available
- Age >= 18 years
- Performance status: Adult Subjects: Eastern Cooperative Oncology Group (ECOG) >= 1; Subjects > 10 years of age: Karnofsky >= 80%; For CNS cohort, ECOG ≥ 2.
- Absolute neutrophil count (ANC) >= 1000
- Platelets >= 100/mm^3
- Hemoglobin > 8 g/dL
- ANC >= 500 is acceptable if documented bone marrow involvement by disease
- Creatinine clearance (estimated by Cockcroft Gault) or using 24 hour (hr) urine collection >= 50 cc/min
- Total bilirubin =< 2 mg/dL except in subjects with Gilbert's Syndrome in whom total bilirubin must be =< 3.0
- Alanine transaminase (alanine aminotransferase [ALT]/serum glutamic pyruvic transaminase [SGPT]) and aspartate aminotransferase (aspartate aminotransferase [AST]/serum glutamic oxaloacetic transaminase [SGOT]) =< 3 x the upper limit of normal or =< 5 x the upper limit of normal if documented liver involvement by disease
- Cardiac left ventricular ejection fraction >= 45% as determined by an echocardiogram and no clinically significant electrocardiogram (ECG) findings
- Baseline oxygen saturation > 92% on room air
- Prior cancer directed therapy wash-out: at least 2 weeks or 5 half-lives, whichever is shorter must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for radiotherapy within 10 days of apheresis, systemic corticosteroid use within 7 days of apheresis (with the exception of single dose for an allergic reaction), or any other immunosuppressive therapies within 7 days
- No use of lymphodepleting agents including alemtuzumab and antithymocyte globulin for 7 days prior to peripheral blood collection, 5 days prior to CD19 CAR T cell infusion and for 90 days after infusion
Who cannot join
- Presence of supplemental oxygen, cardiac pacemaker
- Known allergic reactions to components of the anti-CD19 CAR T cell product as evidenced by prior documented anaphylactic reaction or other clinical signs and/or symptoms of an allergic reaction as determined by the PI
- Febrile illness within 3 days of admission for lymphodepleting conditioning therapy
- Treatment with another investigational drug or other investigational intervention within 2 weeks of apheresis
- Primary immunodeficiency
- History of autoimmune diseases (ex: Crohn's, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's) resulting in end organ damage or requiring systemic immunosuppressive or systemic disease modifying agents within the last two years prior to enrollment
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- Autologous transplant within 6 weeks and allogeneic transplant within 3 months of planned CAR T cell infusion
- Recipient of CD19 CAR T cell therapy outside of this protocol
- Active central nervous system or meningeal involvement by tumor. Subjects with untreated brain metastases/central nervous system (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 involvement must be in a documented remission by cerebrospinal fluid (CSF) evaluation and contrast-enhanced magnetic resonance imaging (MRI) for at least 30 days prior to study enrollment
- History of active malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast)
- Active human immunodeficiency virus (HIV) infection documented by positive viral load. HIV-positive patients with undetectable viral load are not excluded.
- Subjects with uncontrolled concurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or 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. Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) weeks after receiving the CAR-T cell infusion
- Diagnosis of myelodysplasia on any 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
About this study
Official title: A Phase I Study to Evaluate the Safety of Escalating Doses of Lymphodepleting Conditioning Chemotherapy Prior to CD19 Chimeric Antigen Receptor T Cells in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma
This phase I trial evaluates the best dose, possible benefits and/or side effects of fludarabine and cyclophosphamide with or without rituximab before CD19 chimeric antigen receptor T cells in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or has not responded to previous treatment (refractory). T-cells are a normal part of the immune system. To make the T-cell medication, T-cells are taken from the blood and altered in a laboratory. They are then returned to the body. The altered T-cells will latch on to a specific part of the cancer cells and hopefully kill them. Once the T-cells have been altered in the laboratory, they are called "CAR T-cells." CAR is short for "chimeric antigen receptors." These are structures on the surface of cells that allow the altered T-Cells to find and destroy the cancer cells. Another part of the T-Cell medication is called "CD19." This part is called a "biomarker." Biomarkers help doctors determine whether a cancer is getting worse and whether medications are working to stop it. The chemotherapy drugs that are given before the T-Cell therapy are cyclophosphamide, fludarabine and rituximab. Rituximab is an immunotherapy drug. These chemotherapy drugs will reduce the number of normal (unaltered) T-Cells in the body to make room for the altered T-cells to kill the cancer cells. Giving fludarabine and cyclophosphamide with or without rituximab before CD19 CAR T cell therapy may help improve response to CD19 CAR T cell therapy in patients with diffuse large B-cell lymphoma.
Read the detailed description
PRIMARY OBJECTIVES:I. To examine the feasibility to manufacture autologous CD19 CAR T cells at a minimum target dose of 1.0 x 10^6 cells/kilogram using the CliniMACS automated system.II. To determine the safety of administering high-dose conditioning chemotherapy with cyclophosphamide and fludarabine with rituximab prior to CD19 CAR-T cell therapy in patients with relapsed (R)/refractory (R) diffuse large B cell lymphoma (DLBCL) and to find the recommended regimen after phase II dose for this therapy.III. To determine the safety of infusion of chimeric antigen receptor T cells targeting CD19 in adults with R/R DLBCL.
SECONDARY OBJECTIVES:I. To describe the toxicities related to CD19 targeted CAR T cells.II. To describe the overall response rate (ORR) and complete response (CR) rate of relapsed DLBCL treated with CD19 CAR T cells.III. To assess other response variables including overall survival (OS), progression free survival (PFS), and event free survival (EFS).
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 6 dose levels.
DOSE LEVEL 1: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes daily and cyclophosphamide IV over 60 minutes daily on days -5 to -3. Patients also receive CD19 CAR T cells IV on day 0.
DOSE LEVEL 2: Patients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -3, and cyclophosphamide IV over 60 minutes on days -5 to -3. Patients also receive CD19 CAR T cells IV on day 0.
DOSE LEVEL 3: Patients receive fludarabine phosphate IV over 30 minutes daily on days -3 to -5 and cyclophosphamide IV over 60 minutes daily on day -5. Patients also receive CD19 CAR T cells IV on day 0.DOSE LEVEL 4: Patients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -3, and cyclophosphamide IV over 60 minutes on day -5. Patients also receive CD19 CAR T cells IV on day 0.
DOSE LEVEL 5: Patients receive fludarabine phosphate IV over 30 minutes daily on days -5 to -1 and cyclophosphamide IV over 60 minutes daily on days -5 and -4. Patients also receive CD19 CAR T cells IV on day 0.
DOSE LEVEL 6: Patients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -1, and cyclophosphamide IV over 60 minutes on days -5 and -4. Patients also receive CD19 CAR T cells IV on day 0.After completion of study treatment, patients are followed up at 30, 60, and 90 days, 6 and 12 months, and then annually for up to 15 years.
- Being tested
- Chimeric Antigen Receptor T-Cell Therapy, Cyclophosphamide, Fludarabine Phosphate, Rituximab
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chimeric Antigen Receptor T-Cell TherapyBiological
Also called CAR T Infusion, CAR T Therapy, CAR T-cell Therapy, Chimeric Antigen Receptor T-cell Infusion
Given CD19 CAR T cells IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara
Given IV
RituximabBiological
Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Dose level 1 (fludarabine, cyclophosphamide, CD19 CAR T) | Experimental | Patients receive fludarabine phosphate IV over 30 minutes daily and cyclophosphamide IV over 60 minutes daily on days -5 to -3. Patients also receive CD19 CAR T cells IV on day 0. Receives: Biological: Chimeric Antigen Receptor T-Cell Therapy; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate |
| Dose level 2 (rituximab, fludarabine, cyclophosphamide, CAR T) | Experimental | Patients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -3, and cyclophosphamide IV over 60 minutes on days -5 to -3. Patients also receive CD19 CAR T cells IV on day 0. Receives: Biological: Chimeric Antigen Receptor T-Cell Therapy; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Biological: Rituximab |
| Dose level 3 (fludarabine, cyclophosphamide, CD19 CAR T) | Experimental | Patients receive fludarabine phosphate IV over 30 minutes daily on days -3 to -5 and cyclophosphamide IV over 60 minutes daily on day -5. Patients also receive CD19 CAR T cells IV on day 0. Receives: Biological: Chimeric Antigen Receptor T-Cell Therapy; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate |
| Dose level 4 (rituximab, fludarabine, cyclophosphamide, CAR T) | Experimental | Patients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -3, and cyclophosphamide IV over 60 minutes on day -5. Patients also receive CD19 CAR T cells IV on day 0. Receives: Biological: Chimeric Antigen Receptor T-Cell Therapy; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Biological: Rituximab |
| Dose level 5 (fludarabine, cyclophosphamide, CD19 CAR T) | Experimental | Patients receive fludarabine phosphate IV over 30 minutes daily on days -5 to -1 and cyclophosphamide IV over 60 minutes daily on days -5 and -4. Patients also receive CD19 CAR T cells IV on day 0. Receives: Biological: Chimeric Antigen Receptor T-Cell Therapy; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate |
| Dose level 6 (rituximab, fludarabine, cyclophosphamide, CAR T) | Experimental | Patients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -1, and cyclophosphamide IV over 60 minutes on days -5 and -4. Patients also receive CD19 CAR T cells IV on day 0. Receives: Biological: Chimeric Antigen Receptor T-Cell Therapy; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Biological: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of products successfully manufactured meeting the established release criteria with a goal of at least 1.0 x 10^6 cells/kilogram
Measured: Up to 15 years
Incidence and severity of adverse events related to lymphodepleting chemotherapy and or CD19 chimeric antigen receptor (CAR) T cells
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate. Toxicity data by type and severity will be summarized by frequency tables.
Measured: 2 months
Dose limiting toxicities (DLTs) related to lymphodepleting chemotherapy and or CD19 CAR T cells
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate. Toxicity data by type and severity will be summarized by frequency tables.
Measured: 2 months
Maximum tolerated dose
Measured: 2 months
Incidence and severity of DLT associated with infusion of CD19 CAR T cells (infusion reactions)
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate. Toxicity data by type and severity will be summarized by frequency tables.
Measured: 2 months
Secondary outcomes (6)
Incidence of toxicities related to CD19 CAR T cells
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate. Toxicity data by type and severity will be summarized by frequency tables.
Measured: Up to 15 years
Overall response rate
Defined as the percentage of patients that achieve partial response or complete response. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate.
Measured: At 3 months after completion of CAR-T therapy
Complete response rate
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate.
Measured: At 3 months after completion of CAR T therapy
Overall survival
Will be estimated using Kaplan and Meier methods. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Measured: From the start of the conditioning lymphodepletion chemotherapy on day -6 until death, assessed at 1 year
Progression free survival
Will be estimated using Kaplan and Meier methods. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Measured: From the start of the conditioning lymphodepletion chemotherapy regimen until the documentation of disease progression or death due to any cause, whichever occurs first, assessed at 1 year
Event free survival
Will be estimated using Kaplan and Meier methods. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Measured: From the date of day -6 of lymphodepleting conditioning therapy to the date of first documented progression, initiation of new anti-lymphoma treatment, or death, assessed at 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2021
- Study start17 Sep 2021
- Primary completion15 May 2027 (estimated)
- Study completion15 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Mehrdad Abedi, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05052528
- Sponsor's protocol ID
- UCDCC#299
- Other IDs
- NCI-2021-07396, UCDCC#299, P30CA093373
- Status last verified
- Oct 2026
- First submitted
- 13 Sep 2021
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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 I Study to Evaluate the Safety of Escalating Doses of Lymphodepleting Conditioning Chemotherapy Prior to CD19 Chimeric Antigen Receptor T Cells in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma
- ClinicalTrials.gov ID
- NCT05052528
- Acronym / sponsor ID
- UCDCC#299
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 17 Sep 2021 (actual)
- Primary completion
- 15 May 2027 (estimated)
- Study completion
- 15 Dec 2027 (estimated)
- First posted
- 22 Sep 2021 (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 phase I trial evaluates the best dose, possible benefits and/or side effects of fludarabine and cyclophosphamide with or without rituximab before CD19 chimeric antigen receptor T cells in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or has not responded to previous treatment (refractory). T-cells are a normal part of the immune system. To make the T-cell medication, T-cells are taken from the blood and altered in a laboratory. They are then returned to the body. The altered T-cells will latch on to a specific part of the cancer cells and hopefully kill them. Once the T-cells have been altered in the laboratory, they are called "CAR T-cells." CAR is short for "chimeric antigen receptors." These are structures on the surface of cells that allow the altered T-Cells to find and destroy the cancer cells. Another part of the T-Cell medication is called "CD19." This part is called a "biomarker." Biomarkers help doctors determine whether a cancer is getting worse and whether medications are working to stop it. The chemotherapy drugs that are given before the T-Cell therapy are cyclophosphamide, fludarabine and rituximab. Rituximab is an immunotherapy drug. These chemotherapy drugs will reduce the number of normal (unaltered) T-Cells in the body to make room for the altered T-cells to kill the cancer cells. Giving fludarabine and cyclophosphamide with or without rituximab before CD19 CAR T cell therapy may help improve response to CD19 CAR T cell therapy in patients with diffuse large B-cell lymphoma.
Detailed description
PRIMARY OBJECTIVES:I. To examine the feasibility to manufacture autologous CD19 CAR T cells at a minimum target dose of 1.0 x 10^6 cells/kilogram using the CliniMACS automated system.II. To determine the safety of administering high-dose conditioning chemotherapy with cyclophosphamide and fludarabine with rituximab prior to CD19 CAR-T cell therapy in patients with relapsed (R)/refractory (R) diffuse large B cell lymphoma (DLBCL) and to find the recommended regimen after phase II dose for this therapy.III. To determine the safety of infusion of chimeric antigen receptor T cells targeting CD19 in adults with R/R DLBCL.
SECONDARY OBJECTIVES:I. To describe the toxicities related to CD19 targeted CAR T cells.II. To describe the overall response rate (ORR) and complete response (CR) rate of relapsed DLBCL treated with CD19 CAR T cells.III. To assess other response variables including overall survival (OS), progression free survival (PFS), and event free survival (EFS).
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 6 dose levels.
DOSE LEVEL 1: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes daily and cyclophosphamide IV over 60 minutes daily on days -5 to -3. Patients also receive CD19 CAR T cells IV on day 0.
DOSE LEVEL 2: Patients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -3, and cyclophosphamide IV over 60 minutes on days -5 to -3. Patients also receive CD19 CAR T cells IV on day 0.
DOSE LEVEL 3: Patients receive fludarabine phosphate IV over 30 minutes daily on days -3 to -5 and cyclophosphamide IV over 60 minutes daily on day -5. Patients also receive CD19 CAR T cells IV on day 0.DOSE LEVEL 4: Patients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -3, and cyclophosphamide IV over 60 minutes on day -5. Patients also receive CD19 CAR T cells IV on day 0.
DOSE LEVEL 5: Patients receive fludarabine phosphate IV over 30 minutes daily on days -5 to -1 and cyclophosphamide IV over 60 minutes daily on days -5 and -4. Patients also receive CD19 CAR T cells IV on day 0.
DOSE LEVEL 6: Patients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -1, and cyclophosphamide IV over 60 minutes on days -5 and -4. Patients also receive CD19 CAR T cells IV on day 0.After completion of study treatment, patients are followed up at 30, 60, and 90 days, 6 and 12 months, and then annually for up to 15 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Dose level 1 (fludarabine, cyclophosphamide, CD19 CAR T) | Experimental | Biological: Chimeric Antigen Receptor T-Cell Therapy, Drug: Cyclophosphamide, Drug: Fludarabine PhosphatePatients receive fludarabine phosphate IV over 30 minutes daily and cyclophosphamide IV over 60 minutes daily on days -5 to -3. Patients also receive CD19 CAR T cells IV on day 0. |
| Dose level 2 (rituximab, fludarabine, cyclophosphamide, CAR T) | Experimental | Biological: Chimeric Antigen Receptor T-Cell Therapy, Drug: Cyclophosphamide, Drug: Fludarabine Phosphate, Biological: RituximabPatients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -3, and cyclophosphamide IV over 60 minutes on days -5 to -3. Patients also receive CD19 CAR T cells IV on day 0. |
| Dose level 3 (fludarabine, cyclophosphamide, CD19 CAR T) | Experimental | Biological: Chimeric Antigen Receptor T-Cell Therapy, Drug: Cyclophosphamide, Drug: Fludarabine PhosphatePatients receive fludarabine phosphate IV over 30 minutes daily on days -3 to -5 and cyclophosphamide IV over 60 minutes daily on day -5. Patients also receive CD19 CAR T cells IV on day 0. |
| Dose level 4 (rituximab, fludarabine, cyclophosphamide, CAR T) | Experimental | Biological: Chimeric Antigen Receptor T-Cell Therapy, Drug: Cyclophosphamide, Drug: Fludarabine Phosphate, Biological: RituximabPatients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -3, and cyclophosphamide IV over 60 minutes on day -5. Patients also receive CD19 CAR T cells IV on day 0. |
| Dose level 5 (fludarabine, cyclophosphamide, CD19 CAR T) | Experimental | Biological: Chimeric Antigen Receptor T-Cell Therapy, Drug: Cyclophosphamide, Drug: Fludarabine PhosphatePatients receive fludarabine phosphate IV over 30 minutes daily on days -5 to -1 and cyclophosphamide IV over 60 minutes daily on days -5 and -4. Patients also receive CD19 CAR T cells IV on day 0. |
| Dose level 6 (rituximab, fludarabine, cyclophosphamide, CAR T) | Experimental | Biological: Chimeric Antigen Receptor T-Cell Therapy, Drug: Cyclophosphamide, Drug: Fludarabine Phosphate, Biological: RituximabPatients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -1, and cyclophosphamide IV over 60 minutes on days -5 and -4. Patients also receive CD19 CAR T cells IV on day 0. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Commercial CD19 CAR T cell product not available for the patient
- Male or female, aged >= 18
- In good general health as evidenced by medical history or as determined by the principal investigator (PI)
Key exclusion criteria (15 listed)
- Presence of supplemental oxygen, cardiac pacemaker
- Known allergic reactions to components of the anti-CD19 CAR T cell product as evidenced by prior documented anaphylactic reaction or other clinical signs and/or symptoms of an allergic reaction as determined by the PI
- Febrile illness within 3 days of admission for lymphodepleting conditioning therapy
- Treatment with another investigational drug or other investigational intervention within 2 weeks of apheresis
- Primary immunodeficiency
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 |
|---|---|---|
| Chimeric Antigen Receptor T-Cell TherapyAlso: CAR T Infusion, CAR T Therapy, CAR T-cell Therapy, Chimeric Antigen Receptor T-cell InfusionGiven CD19 CAR T cells IV | Biological | Dose level 1 (fludarabine, cyclophosphamide, CD19 CAR T), Dose level 2 (rituximab, fludarabine, cyclophosphamide, CAR T), Dose level 3 (fludarabine, cyclophosphamide, CD19 CAR T), Dose level 4 (rituximab, fludarabine, cyclophosphamide, CAR T), Dose level 5 (fludarabine, cyclophosphamide, CD19 CAR T), Dose level 6 (rituximab, fludarabine, cyclophosphamide, CAR T) |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV | Drug | Dose level 1 (fludarabine, cyclophosphamide, CD19 CAR T), Dose level 2 (rituximab, fludarabine, cyclophosphamide, CAR T), Dose level 3 (fludarabine, cyclophosphamide, CD19 CAR T), Dose level 4 (rituximab, fludarabine, cyclophosphamide, CAR T), Dose level 5 (fludarabine, cyclophosphamide, CD19 CAR T), Dose level 6 (rituximab, fludarabine, cyclophosphamide, CAR T) |
| Fludarabine PhosphateAlso: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, FludaraGiven IV | Drug | Dose level 1 (fludarabine, cyclophosphamide, CD19 CAR T), Dose level 2 (rituximab, fludarabine, cyclophosphamide, CAR T), Dose level 3 (fludarabine, cyclophosphamide, CD19 CAR T), Dose level 4 (rituximab, fludarabine, cyclophosphamide, CAR T), Dose level 5 (fludarabine, cyclophosphamide, CD19 CAR T), Dose level 6 (rituximab, fludarabine, cyclophosphamide, CAR T) |
| RituximabAlso: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 AntibodyGiven IV | Biological | Dose level 2 (rituximab, fludarabine, cyclophosphamide, CAR T), Dose level 4 (rituximab, fludarabine, cyclophosphamide, CAR T), Dose level 6 (rituximab, fludarabine, cyclophosphamide, CAR T) |
Primary outcome
Proportion of products successfully manufactured meeting the established release criteria with a goal of at least 1.0 x 10^6 cells/kilogram
Time frame: Up to 15 years
Incidence and severity of adverse events related to lymphodepleting chemotherapy and or CD19 chimeric antigen receptor (CAR) T cells
Time frame: 2 months
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate. Toxicity data by type and severity will be summarized by frequency tables.
Dose limiting toxicities (DLTs) related to lymphodepleting chemotherapy and or CD19 CAR T cells
Time frame: 2 months
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate. Toxicity data by type and severity will be summarized by frequency tables.
Maximum tolerated dose
Time frame: 2 months
Incidence and severity of DLT associated with infusion of CD19 CAR T cells (infusion reactions)
Time frame: 2 months
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate. Toxicity data by type and severity will be summarized by frequency tables.
6 secondary outcomes
Incidence of toxicities related to CD19 CAR T cells
Time frame: Up to 15 years
Overall response rate
Time frame: At 3 months after completion of CAR-T therapy
Complete response rate
Time frame: At 3 months after completion of CAR T therapy
Overall survival
Time frame: From the start of the conditioning lymphodepletion chemotherapy on day -6 until death, assessed at 1 year
Progression free survival
Time frame: From the start of the conditioning lymphodepletion chemotherapy regimen until the documentation of disease progression or death due to any cause, whichever occurs first, assessed at 1 year
Event free survival
Time frame: From the date of day -6 of lymphodepleting conditioning therapy to the date of first documented progression, initiation of new anti-lymphoma treatment, or death, assessed at 1 year
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.
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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. This study is not recruiting at the moment.
Mehrdad Abedi principal investigator
University of California, Davis
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 Chimeric Antigen Receptor T-Cell Therapy, Cyclophosphamide and Fludarabine Phosphate in people with Recurrent Diffuse Large B-Cell Lymphoma and Refractory Diffuse Large B-Cell Lymphoma, run by University of California, Davis 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 25 inclusion and 15 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: under way, not looking for participants, 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of products successfully manufactured meeting the established release criteria with a goal of at least 1.0 x 10^6 cells/kilogram (time frame: Up to 15 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.