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CD19 PositivePhase 1NCT04007029

Modified Immune Cells (CD19/CD20 CAR-T Cells) in Treating Patients With Recurrent or Refractory B-Cell Lymphoma or Chronic Lymphocytic Leukemia

A Phase 1 study testing Chimeric Antigen Receptor T-Cell Therapy, Cyclophosphamide and Fludarabine Phosphate in people with CD19 Positive and CD20 Positive, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of CD19/CD20 chimeric antigen receptor (CAR) T-cells when given together with chemotherapy, and to see how effective they are in treating patients with non-Hodgkin's B-cell lymphoma or chronic lymphocytic leukemia that has come back (recurrent) or has not… Read more about this study

Who is it for?
Ages 18 to 70 years
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
24 participants
Where
1 siteUnited States
Study dates
4 Oct 2019to 1 Aug 2028
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), or small lymphocytic lymphoma (SLL) that is refractory to standard-of-care options
  • DLBCL and PMBCL: primary refractory; relapsed after two prior lines of therapy
  • MCL, FL, CLL, and SLL: primary refractory; relapsed after three or more prior rounds of therapy
  • > 30% positivity in malignant cells of either CD19 and/or CD20
  • Minimum tumor burden of 1.5 cm^3 for lymphoma
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
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  • Adequate bone marrow and major organ function to undergo a T cell transplant determined within 30?60 days prior to enrollment using standard phase I criteria for organ function. Blood may be evaluated while a patient is receiving growth factor support. Patients will be re-evaluated for organ function within 14 days of beginning conditioning chemotherapy
  • Absolute neutrophil count (ANC) >= 1 x 10^9 cells/L (within 30-60 days prior to enrollment)
  • Platelets >= 75 x 10^9/L (within 30-60 days prior to enrollment)
  • Hemoglobin >= 8 g/dL (with or without transfusion) (within 30-60 days prior to enrollment)
  • Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x upper limit of normal (ULN) (within 30-60 days prior to enrollment)
  • Total bilirubin =< 2 x ULN (except patients with documented Gilbert?s syndrome) (within 30-60 days prior to enrollment)
  • Creatinine < 2 mg/dL (or a glomerular filtration rate > 45) (within 30-60 days prior to enrollment)
  • Must be willing and able to accept at least one leukapheresis procedure
  • Must be willing and able to provide written informed consent

Who cannot join

  • Inability to purify >= 1 x 10^7 T cells from leukapheresis product
  • Previously known hypersensitivity to any of the agents used in this study; known sensitivity to cyclophosphamide or fludarabine
  • Received systemic treatment for cancer, including immunotherapy, within 14 days prior to initiation of conditioning chemotherapy administration within this protocol. Patients who have received anti-CD19 CAR T-cells will be excluded from this trial. Consistent with current trials, patients may otherwise be given bridging therapy at the discretion of the lead study investigator
  • Patients who have received an allograft transplant will NOT be allowed to participate in the trial. Patients who have received an autologous transplant will not be excluded and may participate in the trial
  • Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 2 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed)
  • Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lymphodepletion. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
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  • Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
  • Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
  • Known clinically active brain metastases. Prior evidence of brain metastasis successfully treated with surgery or radiation therapy will not be exclusion for participation as long as they are deemed under control at the time of study enrollment and there are no neurological signs of potential brain metastases. A brain magnetic resonance imaging (MRI) scan taken within 60 days of screening may be used, otherwise a brain MRI must be performed to confirm absence of brain metastases
  • A Tiffeneau-Pinelli index < 70% of the predicted value. Subjects will be excluded if pulmonary function tests indicate they have insufficient pulmonary capability
  • A left ventricular ejection fraction as determined by an echocardiogram lower than 40% would preclude participation
  • Pregnancy or breast-feeding. Female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and for 6 months afterwards. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) at screening and again within 14 days from starting the conditioning chemotherapy. The definition of effective contraception will be based on the judgment of the study investigators. Patients who are breastfeeding are not allowed on this study
  • History of other malignancy in the past 3 years with the following exceptions:
  • Malignancy treated with curative intent and no known active disease
  • Adequately treated non-melanoma skin cancer without evidence of disease
  • Adequately treated cervical carcinoma in situ without evidence of disease
  • Adequately treated breast ductile carcinoma without evidence of disease
  • Prostate cancer with a Gleason score less than 6 with undetectable prostate specific antigen over 12 months
  • Adequately treated urothelial non-invasive carcinoma or carcinoma in situ
  • Similar neo-plastic conditions with an expectation of greater than 95% disease free survival

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: Study of CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR)-T Cells for the Treatment of Relapsed or Refractory B-Cell Lymphomas and Chronic Lymphocytic Leukemia (CD20 - Cluster of Differentiation Antigen 20)

This phase I trial studies the side effects and best dose of CD19/CD20 chimeric antigen receptor (CAR) T-cells when given together with chemotherapy, and to see how effective they are in treating patients with non-Hodgkin's B-cell lymphoma or chronic lymphocytic leukemia that has come back (recurrent) or has not responded to treatment (refractory). In CAR-T cell therapy, a patient's white blood cells (T cells) are changed in the laboratory to produce an engineered receptor that allows the T cell to recognize and respond to CD19 and CD20 proteins. CD19 and CD20 are commonly found on non-Hodgkin?s B-cell lymphoma and chronic lymphocytic leukemia cells. Chemotherapy drugs such as fludarabine phosphate and cyclophosphamide can control cancer cells by killing them, by preventing their growth, or by stopping them from spreading. Combining CD19/CD20 CAR-T cells and chemotherapy may help treat patients with recurrent or refractory B-cell lymphoma or chronic lymphocytic leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety of the autologous anti-CD19/anti-CD20 CAR-expressing naive/memory T cells (CART19/20), including determination of the maximum tolerated dose and assessment for replication competent lentivirus (RCL).

SECONDARY OBJECTIVES:

  1. Clinical response. Ia. Overall response rate. Ib. Duration of remission. Ic. Progression-free survival. Id. Overall survival. II. CD19/CD20 bispecific CAR transgenic T-cell persistence. IIa. T-cell monitoring and analyses. IIb. Evidence of B-cell aplasia.

EXPLORATORY OBJECTIVES:

  1. To determine the serum levels of cytokines associated with cytokine release syndrome (CRS) in subjects exhibiting > grade-2 CRS following CART19/20 cell treatment.

OUTLINE: This is a dose-escalation study of CD19/CD20 CAR-T cells.

CONDITIONING CHEMOTHERAPY: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes and cyclophosphamide IV over 60 minutes 5, 4, and 3 days before cell infusion.

T-CELL INFUSION: Patients receive CD19/CD20 CAR-T cells IV on day 0. Patients with cytokine release syndrome may also receive tocilizumab IV on day 2 at the discretion of the clinical investigator.

After completion of study treatment, patients are followed up daily for 14 days, on days 30, 45, 60, 70, 90, and 120, every 3 months for 2 years, every 6 months for 3 years, and then annually for a minimum of 15 years.

Being tested
Chimeric Antigen Receptor T-Cell Therapy, Cyclophosphamide, Fludarabine Phosphate, Tocilizumab
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell

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 Autologous anti-CD19/anti-CD20 CAR-expressing naive/memory 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

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP fludarabine: 2-Fluoroadenine 9-beta-D-Arabinofuranoside 5'-Monophosphate, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • TocilizumabBiological

    Also called Actemra, Immunoglobulin G1, Anti-(Human Interleukin 6 Receptor) (Human-Mouse Monoclonal MRA Heavy Chain), Disulfide with Human-Mouse Monoclonal MRA Kappa-Chain, Dimer, MRA (myeloma receptor antibody), R-1569

    Given IV

Study groups in NCT04007029
Study groupRoleWhat they receive
Treatment (fludarabine, cyclophosphamide, CD19/CD20 T-cells)ExperimentalCONDITIONING CHEMOTHERAPY: Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 60 minutes 5, 4, and 3 days before cell infusion. T-CELL INFUSION: Patients receive CD19/CD20 CAR-T cells IV on day 0. Patients with cytokine release syndrome may also receive tocilizumab IV on day 2 at the discretion of the clinical investigator.
Receives: Biological: Chimeric Antigen Receptor T-Cell Therapy; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Biological: Tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

    Will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, with the exception of cytokine release syndrome (CRS), which will be graded on the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for CRS scale. Simple descriptive statistics will be used to summarize toxicities observed after each transgenic T-cell infusion in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by CTCAE toxicity table) and minimum or maximum values for laboratory measures, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects. Adverse events will be tabulated by treatment group and will include the number of patients for whom the event occurred, the rate of occurrence, and the severity and relationship to study drug.

    Measured: Up to 28 days from infusion

  2. Dose-limiting toxicities

    Will be assessed per CTCAE version 5.0 with the exception of CRS as mentioned above.

    Measured: Up to 28 days from infusion

Secondary outcomes (8)

  1. Clinical response

    Descriptive statistics including simple summary measures and plots appropriate for longitudinal data will be used.

    Measured: Up to 15 years

  2. Duration of remission

    Descriptive statistics including simple summary measures and plots appropriate for longitudinal data will be used. Will also be summarized descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum). Figures showing the Kaplan-Meier estimates will also be presented.

    Measured: Time from complete remission (CR)/partial remission (PR) measurement criteria are first met until the first date that recurrent or progressive disease is objectively documented, or until death, assessed up to 15 years

  3. Objective response rate (ORR)

    Descriptive statistics including simple summary measures and plots appropriate for longitudinal data will be used. ORR and the individual rate for CR and PR will be summarized with the frequency count and the percentage of subjects in each category, along with a 2-sided 95% exact confidence interval.

    Measured: Up to 15 years

  4. Progression-free survival

    Descriptive statistics including simple summary measures and plots appropriate for longitudinal data will be used. Will also be summarized descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum). Figures showing the Kaplan-Meier estimates will also be presented.

    Measured: From time of study entry to documentation of objective disease progression or death due to any cause assessed up to 15 years

  5. Overall survival (OS)

    Descriptive statistics including simple summary measures and plots appropriate for longitudinal data will be used. Will be summarized with figures using the Kaplan-Meier method. The Kaplan-Meier estimates for the 1-year OS (rates and the 2-sided 95% confidence interval of the rates using the Greenwood?s formula will be reported. Will also be summarized descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum).

    Measured: From date of enrollment until death, assessed up to 15 years

  6. Chimeric antigen receptor (CAR) T-cell (T) 19/20 bispecific transgenic T-cell persistence

    Descriptive statistics of T-cell counts over time, including simple summary measures and plots appropriate for longitudinal data will be used.

    Measured: Up to 5 years post-infusion

  7. Frequency of T cell phenotypic markers on CART19/20 cells using flow cytometry

    The frequency of CART19/20 cell properties will be assessed using flow cytometry to indicate the % and/or total number of CART19/20 cells expressing critical markers, for example CD3 (cluster of differentiation 3), CD4 (cluster of differentiation 4), and CD8 (cluster of differentiation 8), to determine correlations between CART19/20 properties, treatment efficacy, and CART19/20 cell persistence.

    Measured: Up to 5 years post-infusion

  8. Duration of B-cell aplasia following CART19/20 infusion.

    The duration of time patients experience B-cell aplasia (<3% of lymphocytes in the peripheral blood expressing either CD19 or CD20, measured with immunohistochemistry (IHC) and/or flow cytometry) following infusion of CART19/20 cells will be determined.

    Measured: Up to 2 years post-infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jul 2019
  2. Study start4 Oct 2019
  3. Primary completion1 Aug 2027 (estimated)
  4. Study completion1 Aug 2028 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04007029
Sponsor's protocol ID
18-001989
Other IDs
NCI-2019-03190, 18-001989
Status last verified
Aug 2026
First submitted
20 Jun 2019
Last updated
20 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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 CD19 Positive and CD20 Positive, run by Jonsson Comprehensive Cancer Center 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 15 inclusion and 20 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 20 Aug 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?

Incidence of adverse events (time frame: Up to 28 days from infusion). 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 NCT04007029.

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 20 Aug 2026.

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