Fludarabine and Cyclophosphamide With or Without Rituximab Before CD19 CAR T Cells for Relapsed or Refractory Diffuse Large B-Cell Lymphoma
This study is looking at a treatment for diffuse large B-cell lymphoma that has come back (relapsed) or hasn't responded to previous treatments (refractory). It combines fludarabine and cyclophosphamide, with or without rituximab, before giving CD19 chimeric antigen receptor (CAR) T cells. CAR T cells are your own immune cells that have been specially trained in a lab to find and fight cancer. The study aims to see how safe these treatments are together and if they can successfully make enough CAR T cells. You may be able to join if you are 18 or older, in good health, and commercial CD19 CAR T cell therapy isn't available to you. The study plans to enroll 36 participants.
- Study design
- This is an interventional study, meaning you will receive a specific treatment. It is a dose-escalation study, meaning different groups of participants will receive different doses of the treatments.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- Participants will be followed for adverse events for 2 months, and the success of CAR T cell manufacturing will be monitored for up to 15 years.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05052528
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
Recruiting
PHASE1Ages 18+InterventionalTreatmentUniversity of California, DavisInvestigator-initiated
~36 participants
Updated 2026-07-17 on ClinicalTrials.gov
What's tested:Chimeric Antigen Receptor T-Cell TherapyCyclophosphamideFludarabine PhosphateRituximab
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Proportion of products successfully manufactured meeting the established release criteria with a goal of at least 1.0 x 10^6 cells/kilogram
Measured over Up to 15 years
+4 more outcomes measured
Conditions
Where it's being run
1 sites across 1 statesCalifornia1
Study leadership
- Mehrdad Abedi · PRINCIPAL_INVESTIGATOR · University of California, Davis
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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)
What this trial measures
- Proportion of products successfully manufactured meeting the established release criteria with a goal of at least 1.0 x 10^6 cells/kilogramUp to 15 years
- Incidence and severity of adverse events related to lymphodepleting chemotherapy and or CD19 chimeric antigen receptor (CAR) T cells2 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 cells2 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 dose2 months
- Incidence and severity of DLT associated with infusion of CD19 CAR T cells (infusion reactions)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.