AzTrials
AzTrials

Lymphoma, B-CellPhase 1NCT03593109

A Single-center Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LCAR-L10D Cell Formulations Targeting CD19 and CD22 in Patients With CD19- and/or CD22-Positive Relapsed/Refractory B-cell Lymphoma

A Phase 1 study testing Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy in people with Lymphoma, B-Cell, run by Second Affiliated Hospital of Xi'an Jiaotong University at 1 site in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a prospective, single-arm, single-center, open-label, single-dose dose finding and expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profile of LCAR-L10D in subjects with CD19- and/or CD22-positive relapsed/refractory B-cell lymphoma after prior adequate standard… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Lymphoma, B-Cell
What is being tested?
Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteChina
Study dates
30 May 2019to 1 May 2021
Phase
Phase 1
Are there results?
None posted in the registry

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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Volunteer to participate in the clinical study; fully understand and be informed of the information on this study, and sign the written Informed Consent Form (ICF); willing to follow and able to complete all trial procedures.
  • According to the criteria for B-cell lymphoma defined in the National Comprehensive Cancer Network (NCCN) Guidelines for Lymphoma (5th edition 2018), and with CD19- and/or CD22-positive lymphoma cells detected by flow cytometry or immunohistochemistry;
  • Must have at least 1 evaluable or measurable lesion meeting Lugano 2014 criteria [Evaluable lesions: Fluorodeoxyglucose/positron emission tomography (FDG/PET) showed increased local uptake in lymph nodes or extranodal sites (higher than the liver), and PET and/or computed tomography (CT) findings are consistent with lymphoma manifestations. Measurable lesions: defined as nodule lesions with a long diameter greater than 15 or extranodal lesions with a long diameter greater than 10 mm (if the only measurable lesion has been previously treated with radiation therapy, the evidence of radiographic progression after radiation therapy is required), with increased FDG uptake). Absence of measurable lesion and diffuse increase of hepatic FDG uptake should be excluded.
  • Relapsed/refractory BCL (meet one of the following conditions):
  • Subjects in this category had received at least two cycles of two or more lines of standard of care and had been evaluated for best clinical response per Lugano 2014 at the time of enrollment: (one of the following conditions are met)
  • The subject had a best clinical response of PD after the most recent standard chemotherapy;
Show all 29Show fewer
  • The subject had a best clinical response of SD after the most recent standard chemotherapy, but PD occurred when SD persisted for less than 6 months;
  • Recurrence or progression within ≤ 12 months after autologous hematopoietic stem cell transplantation;
  • In one of the following situations, the benefit of the subject may outweigh the risk as judged jointly by the investigator and the partner:
  • The subject had received at least two lines of standard of care, and the best response after the most recent standard chemotherapy was SD, which persisted for less than 6 months, and the evaluable or measurable disease was larger than before but did not achieve PD;
  • The subject had received at least two lines of standard of care, and the best response after the most recent standard chemotherapy was partial response (PR) or higher, but persisted for less than 6 months before progression;
  • The subject had received at least two lines of standard of care and was intolerant to the most recent chemotherapy.
  • All subjects must have received standardized treatment regimens with anti-CD20 monoclonal antibodies (except for those with CD20-negative tumors as determined by the investigator) and anthracyclines. For standardized treatment regimens, please refer to the criteria in the NCCN Guidelines for B-cell Lymphoma (version 5, 2018);
  • Male or female, aged 18-75 years at the time of signing the ICF;
  • Primary laboratory test values met the following criteria to demonstrate adequate organ and bone marrow function without severe hematopoietic abnormalities and heart, lung, liver, renal dysfunction and immunodeficiency:
  • Serum albumin ≥30g/L Haemoglobin ≥ 8.0 g/dL (no red blood cell [RBC] infusion within 7 days prior to laboratory tests; recombinant human erythropoietin is allowed) Absolute neutrophil count ≥ 0.75 × 109/L (growth factor support is allowed but must not have received supportive care within 7 days prior to laboratory tests) Platelet ≥ 40 × 109/L (must not have received blood transfusion support within 7 days prior to laboratory tests) Creatinine clearance ≥ 40 mL/min/1.73 m2, calculated according to Modified Dietary Formula for Renal Disease (Attachment 11) or 24-hour urine collection results.
  • ALT and AST ≤ 3.0 x upper limit of normal (ULN) Total bilirubin ≤ 2.0 × ULN; except for subjects with congenital bilirubinemia, such as Gilbert's syndrome (in this case, direct bilirubin ≤ 1.5 x ULN is required) Coagulation PT and APTT <2ULN SpO2 ≥95%
  • For subjects who meet the inclusion criteria at screening, red blood cell infusion after the first hematology test at screening is allowed to maintain hemoglobin levels ≥ 8.0 g/dL.
  • ECOG performance status of 0-1;
  • Estimated survival time of patients > 90 days;
  • A highly sensitive serum pregnancy test (beta human chorionic gonadotropin [beta-HCG]) must be negative at screening and prior to first treatment with cyclophosphamide and fludarabine in women of childbearing potential.
  • Women of childbearing potential must comply with the following requirements:
  • Subjects must agree to use a highly effective method of contraception (annual failure rate < 1% for continuous and correct use) and agree to use a highly effective method of contraception from signing the informed consent form (ICF) until at least 1 year after receiving infusion of LCAR-L10D cell formulation. Highly effective methods of contraception include:
  • User-independent methods: 1) implantable progesterone contraceptives that inhibit ovulation; 2) intra-uterine devices (IUDs); intrauterine hormone-releasing systems; 3) vasectomies in sexual partners;
  • User-dependent methods: 1) compound (estrogen- and progestogen-containing) hormonal contraceptives that inhibit ovulation: oral, vaginal and transdermal; 2) progesterone contraceptives (oral or injectable) that inhibit ovulation.
  • In addition to highly effective methods of contraception, male subjects should:
  • Agree to use barrier contraception (e.g. condoms plus spermicidal foam/gel/film/emulsion/suppository) upon sexual intercourse with a woman of childbearing potential from signing the ICF to at least 1 year after receiving infusion of the LCAR-L10D cell formulation.
  • Use condoms when having sex with a pregnant woman Women and men must agree not to donate ova (oocytes, oocytes) or sperm during the study and within 1 year after infusion of LCAR-L10D cell formulation.
  • Note: Hormonal contraceptives may interact with study treatment, resulting in decreased contraceptive efficacy.

Who cannot join

  • Subjects who have received any CART cell therapy or other genetically modified T cell therapy;
  • Previous allogeneic stem cell transplantation.
  • Have been diagnosed or treated with other aggressive malignancies other than B-cell lymphoma, with the following exceptions:
  • Malignant tumors that have been treated radically, and no known active disease within ≥ 2 years prior to enrollment; or
  • Non-melanoma skin cancers have been adequately treated without symptom of disease.
  • Previous anti-tumor therapy (prior to apheresis) as follows:
Show all 35Show fewer
  • Targeted therapy, epigenetic therapy, or investigational drug within 14 days or at least 5 half-lives (whichever is shorter), or has used an invasive investigational medical device.
  • Cytotoxic drugs within 14 days.
  • Immunomodulator within 7 days.
  • Monoclonal antibodies to treat BCL within 21 days.
  • Radiation therapy within 14 days.
  • Positive for any one of hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), or human immunodeficiency virus antibody (HIV-Ab)
  • The following cardiac disorders occurred:
  • New York Heart Association (NYHA) phase III or IV congestive heart failure;
  • Myocardial infarction or coronary artery bypass graft (CABG) ≤ 6 months prior to enrollment;
  • History of clinically significant ventricular arrhythmia or unexplained syncope (non-vasovagal or caused by dehydration);
  • History of severe nonischemic cardiomyopathy;
  • Impaired cardiac function (LVEF < 50%) as assessed by echocardiogram or multiple gated acquisition scan (MUGA) (performed ≤ 8 weeks prior to apheresis).
  • Clinically significant pericardial effusion
  • Clinically significant pleural effusion（Excluding caused by lymphoma mass compression or pleural involvement）;
  • Except alopecia or peripheral neuropathy, other toxicity of prior anti-tumor therapy must have improved to baseline or ≤ Grade 1.
  • Patients with serious underlying diseases, such as:
  • Documented serious active viral or bacterial infection, or uncontrolled systemic fungal infections;
  • Active auto-immune diseases or medical history of auto-immune diseases within 3 years;
  • Clear clinical evidence of dementia or altered mental status.
  • Female subjects who become pregnant, are breastfeeding, or plan to become pregnant while participating in the study or within 1 year after receiving study treatment;
  • Male subjects who plan to have a baby while participating in the study or within 1 year after receiving study treatment;
  • Subjects with marked bleeding tendency, e.g, digestive tract hemorrhage, coagulation disorder, hypersplenism (diagnosed by splenomegaly noted by palpation or ultrasonography, cytopenia, and hematopoietic cell hyperplasia in the bone marrow)；
  • The equivalent dose of corticosteroids used cumulatively within 7 days prior to apheresis was ≥ 70 mg prednisone；
  • Concomitant anticancer drugs or therapies (including radiotherapy);
  • Occurrence of a stroke or epileptic seizure within 6 months prior to signing the ICF;
  • Administration of live attenuated vaccine within 4 weeks prior to apheresis;
  • Major surgery within 2 weeks prior to apheresis, or scheduled surgery during the study or within 2 weeks after administration of study treatment. (Note: Subjects who plan to undergo surgery under local anesthesia may participate in the study.)
  • Any condition that is not conducive to the subject's ability to receive or tolerate the planned treatment at the study site, or understand the informed consent form, or any condition that, in the opinion of the investigator, is not in the best interest of the subject (e.g., impairing health), or any condition that may prevent, limit, or confound protocol-specified assessments.
  • Known life threatening allergic reactions, hypersensitivity reactions, or intolerance to LCAR-L10D cell formulation or their excipients, including DMSO (see Investigator's Brochure).

Trial locations and contacts

1 site in 1 country.

China1 site

  • Second Affiliated Hospital of Xi'an Jiaotong University

    Xi'an, Shaanxi, 710000

Other trials in China

About this study

This is a prospective, single-arm, single-center, open-label, single-dose dose finding and expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profile of LCAR-L10D in subjects with CD19- and/or CD22-positive relapsed/refractory B-cell lymphoma after prior adequate standard of care.

Read the detailed description

CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory B-cell malignancies, CD19 and CD22 are proteins usually expressed on the surface of the lymphoma cells. The dual specificity CAR enables the T-cells to recognize and kill the tumor cell through recognition of CD19 and CD22.

Being tested
Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy
Keywords
Chimeric Antigen Receptor T cells, CD19 and CD22
Medical subject headings
Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dual Specificity CD19 and CD22 CAR-T Cell ImmunotherapyDrug

    Patients will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of CAR-T cells. After a pre-treatment lymphodepletion therapy, patients will receive the Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy by intravenous injection.

Study groups in NCT03593109
Study groupRoleWhat they receive
LCAR-L10D treatment groupExperimentalIn LCAR-L10D treatment group, patients will be treated with dual specificity CD19 and CD22 CAR-T cells with a escalation approach, 3 CAR-T dosage will be tested in this study: 0.5×10^6, 1.5×10^6, 5.0×10^6 CAR-T cells/kg.
Receives: Drug: Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy

What is being measured

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

  1. Type, incidence and severity of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs)

    Dose-limiting toxicity (DLT) refers to a drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose. An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment

    Measured: Day 1-90 days after injection

  2. Chimeric Antigen Receptor T（CAR-T）Positive Cell Concentration

    Venous blood samples will be collected for measurement of CAR-T positive cellular concentration

    Measured: Day 1-90 days after injection

Secondary outcomes (7)

  1. Recommended phase 2 dose (RP2D) of this cell therapy

    Recommended Phase 2 dose (RP2D)

    Measured: Day 1-90 days after injection

  2. Overall response rate (ORR) after administration

    Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment via LCAR-L10Dcell infusion, and the objective tumor response rate will be calculated for patients with measurable disease per Lugano 2014 only.

    Measured: 2 years post infusion

  3. Duration of remission (DOR) after administration

    Duration of Remission (DOR) is defined as the time from the first documentation of remission (PR or better) to the first documented disease progression evidence (according to LUGANO 2014 ) of the responders (who achieve PR or better response).

    Measured: 2 years post infusion

  4. Progress Free Survival (PFS) after administration

    Progression Free Survival (PFS) is defined as the time from the date of first infusion of the LCAR-L10Dto the first documented disease progression (according to LUGANO 2014 ) or death (due to any cause), whichever occurs first.

    Measured: 2 years post infusion

  5. Overall Survival (OS) after administration

    Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-L10Dto death of the subject.

    Measured: 2 years post infusion

  6. Time to Response (TTR) after administration

    Time to Response (TTR) is defined as the time from the date of first infusion of LCAR-L10Dto the date of the first response evaluation of the subject who has met all criteria for PR or better.

    Measured: 2 years post infusion

  7. Incidence of anti-LCAR-L10D antibody and positive sample titer

    Venous blood samples will be collected to measure LCAR-L10Dpositive cell concentrations and the transgenic level of LCAR-L10D, at the time points when anti-LCAR-L10D antibody serum samples are evaluated.

    Measured: Day 1-90 days after injection

Timeline

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

  1. First posted19 Jul 2018
  2. Study start30 May 2019
  3. Primary completion1 May 2021
  4. Study completion1 May 2021

Why it stopped: Suitable patients were not recruited

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
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03593109
Sponsor's protocol ID
Legend-CART-201803-Ⅱ
Status last verified
Nov 2020
First submitted
7 Jul 2018
Last updated
1 Nov 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy in people with Lymphoma, B-Cell, run by Second Affiliated Hospital of Xi'an Jiaotong University at 1 site in China.

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 29 inclusion and 35 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: stopped early, as of the sponsor's last update on 1 Nov 2021. 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 China. 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?

The study was stopped early (reason given: Suitable patients were not recruited). Results are not available in the source record.

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?

Type, incidence and severity of dose-limiting toxicities (DLTs) and treatment-emergent adverse events (TEAEs) (time frame: Day 1-90 days after injection). 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 NCT03593109.

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 1 Nov 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in