Recruiting

Phase 1

Fludarabine & CyclophosphamideFludarabine 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

Sponsor:

UCLA

Code:

NCT05052528

Conditions

Recurrent Diffuse Large B-Cell Lymphoma

Refractory Diffuse Large B-Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Chimeric Antigen Receptor T-Cell Therapy

Cyclophosphamide

Fludarabine Phosphate

Rituximab

Study Details

Brief 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 (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.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma

Refractory Diffuse Large B-Cell Lymphoma

Study ID

NCT05052528

Start date

Sep 17, 2021

Status verified date

Jul, 2026

Completion date

Dec 15, 2027

Anticipated

Primary completion date

May 15, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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
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

Exclusion Criteria:

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
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)

Study Design

Enrollment

36 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose level 1 (fludarabine, cyclophosphamide, CD19 CAR T)

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.

experimental: Dose level 2 (rituximab, fludarabine, cyclophosphamide, CAR T)

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.

experimental: Dose level 3 (fludarabine, cyclophosphamide, CD19 CAR T)

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.

experimental: Dose level 4 (rituximab, fludarabine, cyclophosphamide, CAR T)

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.

experimental: Dose level 5 (fludarabine, cyclophosphamide, CD19 CAR T)

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.

experimental: Dose level 6 (rituximab, fludarabine, cyclophosphamide, CAR T)

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.

Interventions

Chimeric Antigen Receptor T-Cell Therapy

Given CD19 CAR T cells IV

Cyclophosphamide

Given IV

Fludarabine Phosphate

Given IV

Rituximab

Given IV

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 ]
Incidence and severity of adverse events related to lymphodepleting chemotherapy and or CD19 chimeric antigen receptor (CAR) T cells [ Time Frame: 2 months ]
Dose limiting toxicities (DLTs) related to lymphodepleting chemotherapy and or CD19 CAR T cells [ Time Frame: 2 months ]
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 ]

Central Contacts and Locations

Central contacts

Office of Clinical Research

916-382-6970 OCRReferral@health.ucdavis.edu

Locations

University of California Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Contacts

Office of Clinical Research

916-382-6970 OCRReferral@health.ucdavis.edu

Principal Investigator:

Mehrdad Abedi

More Information

Sponsor

University of California, Davis

Last update posted

Jul 17, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by University of California, Davis on 2026-07-17.