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Relapsed Large B-cell LymphomaPhase 1/2NCT04836507

Study of Efficacy and Safety of CRC01 in Adult Large B-cell Lymphoma and B-cell Acute Lymphoblastic Leukemia Patients

A Phase 1/2 study testing CRC01, Fludarabine and Cyclophosphamide in people with Relapsed Large B-cell Lymphoma and Refractory Large B-cell Lymphoma, run by Curocell Inc. at 2 sites in South Korea.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a multi-center, phase I/II study to determine the efficacy and safety of CRC01 in adult patients with relapsed or refractory large B-cell lymphoma and B-cell Acute Lymphoblastic Leukemia. Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
CRC01, Fludarabine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
91 participants
Where
2 sitesSouth Korea
Study dates
2 Mar 2021to 26 Sep 2030
Phase
Phase 1/2
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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 19 years of age and provided written informed consent
  • Histologically confirmed following large B-cell lymphomas according to the World Health Organization classification 2017
  • Diffuse large B-cell lymphoma, not otherwise specified Including Large cell transformation from follicular lymphoma (Transformed follicular lymphoma)
  • High-grade B-cell lymphoma, not otherwise specified
  • High-grade B-cell lymphoma with double-hit/triple-hit
  • Primary mediastinal large B cell lymphoma
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  • Relapsed or refractory disease after ≥ two lines of chemotherapy including rituximab, anthracycline and either having failed autologous Hematopoietic stem cell transplantation (ASCT) or being ineligible for or not consenting to ASCT.
  • At least one measurable lesion (Long diameter ≥ 1.5cm)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate renal and hepatic functions based on the laboratory test results
  • Total Bilirubin ≤ 2.0mg/dL with the exception of patients with Gilbert-Meulengracht syndrome; patients with Gilbert-Meulengracht syndrome may be included if their total bilirubin is ≤ 3 X ULN and direct bilirubin ≤ 1.5 X ULN.
  • Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3 X Upper Limit of Normal (ULN) for age with exception of liver metastasis; patients with liver metastasis may be included if their AST and ALT are ≤ 5 X ULN.
  • Serum creatinine ≤ 1.5 X ULN
  • Estimated Glomerular Filtration Rate (eGFR) ≥ 60mL/min/1.73m2
  • Adequate hematologic function without transfusions within 2 weeks prior to screening for the study defined as followings:
  • Hemoglobin > 8.0g/㎗
  • Absolute Neutrophil Count (ANC) > 1,000/㎕
  • Absolute Lymphocyte Count (ALC) ≥ 300/㎕
  • Platelets ≥ 50,000/㎕
  • Must have a minimum level of pulmonary reserve defined as;
  • ≤ Grade 1 dyspnea per Common terminology criteria for adverse events (CTCAE) v5.0
  • pulse oxygenation > 91% on room air
  • Hemodynamically stable, without pericardial effusion and Left Ventricle Ejection Fraction (LVEF) ≥ 50% confirmed by Echocardiogram (ECG) or Multigated Radionuclide Angiography (MUGA)
  • Must have an apheresis product of non-mobilized cells accepted for manufacturing
  • Life expectancy ≥ 12 weeks
  • Women of child-bearing potential and all male participants must agree to use highly effective methods of contraception for at least 12 months following CRC01 infusion and until CRC01 are no longer present by PCR on two consecutive tests
  • ≥ 19 years of age and provided written informed consent to voluntarily participate in this trial
  • Relapsed or refractory B-cell lymphoblastic leukemia with one of the following:
  • Primary refractory: Newly diagnosed and refractory to 2 or more cycles of standard chemotherapy
  • Relapsed within 12 months of the first complete remission
  • Chemorefractory: Refractory to 1 cycle of chemotherapy conducted after relapse
  • Relapsed after or refractory to two or more lines of chemotherapy
  • Relapsed or refractory 100 days after allogeneic HSCT
  • (within 4 weeks prior to screening) Blast of > 5% identified in the BM
  • (within 4 weeks prior to screening) BM or peripheral blood blast confirmed CD19-positive.
  • Specifically, those with prior treatment with any other anti-CD19 therapy must be confirmed to show CD19 ≥ 90%.
  • Philadelphia chromosome positive with one of the following:
  • Unable to take tyrosine kinase inhibitors (TKIs) due to side effects
  • Relapsed or refractory despite treatment with two or more TKIs
  • ECOG performance status of 0-1
  • Confirmed adequate hematologic function defined as follows:
  • Absolute neutrophil count (ANC) ≥ 500/μL. However, exceptions are made in cases where the Investigator determines that cytopenia is related to the leukemia and may be recovered with leukemia treatment.
  • Platelet count ≥ 50,000/μL. However, exceptions are made in cases where the Investigator determines that cytopenia is related to the leukemia and may be recovered with leukemia treatment.
  • Absolute lymphocyte count ≥ 200/μL
  • Adequate renal and hepatic functions confirmed based on the laboratory test results:
  • Total Bilirubin ≤ 2.0 mg/dL (for patients with Gilbert-Meulengracht syndrome, total bilirubin ≤ 3 × ULN and direct bilirubin ≤ 1.5 × ULN)
  • AST and ALT ≤ 3 × ULN
  • Serum creatinine ≤ 1.5 × ULN or eGFR* ≥ 45 mL/min/1.73 m2 *MDRD-GFR (mL/min/1.73 m2) = 186 × (serum creatinine)-1.154 × (age)-0.203 (× 0.742 for females)
  • Confirmed to have a minimum level of pulmonary reserve according to the following criteria:
  • ≤ Grade 1 dyspnea per CTCAE v5.0
  • Pulse oxygenation > 91% on room air
  • Hemodynamically stable, without pericardial effusion, and LVEF ≥ 50% confirmed by ECHO or MUGA scan at Screening
  • Capable of obtaining through leukapheresis non-mobilized cells adequate for CRC01 manufacturing
  • Life expectancy of ≥ 12 weeks
  • Consented to comply with the site visit and test schedules for Primary Follow-up and Secondary Follow-up in accordance with the Protocol for the duration of the Study
  • WOCBP or male subjects who are willing to use appropriate contraceptive methods* for at least 12 months following CRC01 treatment and until CRC01 is no longer detected through two consecutive PCR tests * Hormonal contraceptives, placement of intrauterine system, double barrier method (simultaneous use of contraceptive vaginal diaphragm or cervical cap and male condom, along with spermicide), sterilization (vasectomy, bilateral tubal ligation), etc.

Who cannot join

  • Patients with the following medical history
  • Previous or concurrent malignancy with the following exceptions:
  • Adequately treated basal cell or squamous cell carcinoma without evidence of recurrence for at least 3 years prior to the study
  • In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study
  • A primary malignancy which has been completely resected and in complete remission for ≥ 5 years
  • Unstable angina and/or myocardial infarction within 12 months prior to screening
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  • Thromboembolic events, pulmonary embolism or bleeding diatheses within 6 months prior to screening
  • Hypoxemia, significant pleural effusion or significant EKG findings within 6 months prior to the screening
  • Patients with the following concurrent disease at screening:
  • Central Nervous System (CNS) involvement by malignancy by MRI at screening
  • Active infection with hepatitis B (HBsAg positive. But, in case of HBcAb IgG positive, the patient can be enrolled in this study if he/she takes prophylactic anti-viral agent.)
  • Active infection with hepatitis C (HCV RNA positive)
  • Human immunodeficiency virus (HIV) positive
  • Active neurological auto-immune or inflammatory disorder (e.g. Guillain Barre Syndrome, Amyotrophic Lateral Sclerosis)
  • Ventricular tachycardia and atrial fibrillation with rapid ventricular response not controlled with medical treatment within 3 months prior to screening
  • Rapidly progressing the disease as per investigator's discretion
  • Had major surgery requiring general anesthesia or mechanical ventilation within 4 weeks prior to screening (For video-assisted thoracoscopic surgery (VATS) or open-and-closed (ONC) surgery can be applied with within 2 weeks prior to screening.)
  • Severe infection requiring anti-bacterial, anti-fungal or anti-viral medication or uncontrolled active infection
  • The following treatment history is excluded:
  • Prior treatment with any prior anti-CD19/anti-CD3 therapy or any other anti-CD19 therapy
  • Prior treatment with any adoptive T cell therapy
  • Treatment with any prior gene therapy product
  • Prior allogeneic HSCT
  • Patients on oral anticoagulation therapy
  • Eligible for and consenting to ASCT
  • Use of investigational medicinal product/device within 4 weeks prior to screening
  • Pregnant or lactating women
  • Hypersensitivity reaction to the excipients of CRC01 cell product
  • The following treatments are excluded:
  • Anti-neoplastic therapies including chemotherapy, biologic agents, retinoid therapy, radiotherapy, immune therapy, hormonal therapy, etc. other than lymphodepleting chemotherapy within 2 weeks of leukapheresis and within 2 weeks of CRC01 infusion
  • Steroids: therapeutic doses of steroids must be stopped > 7 days prior to leukapheresis and > 5 days prior to CRC01 infusion. However, the following physiological replacement doses of steroids are allowed: < 6 mg/m2/day hydrocortisone or equivalent
  • Immunosuppression: any immunosuppressive medication must be stopped > 4 weeks prior to leukapheresis and > 4 weeks prior to CRC01 infusion
  • Antibody use including anti-CD20 therapy within 4 weeks prior to CRC01 infusion
  • CNS disease prophylaxis must be stopped > 1 week prior to CRC01 infusion (e.g. intrathecal methotrexate)
  • Cohort B :
  • Patients in Cohort B may not participate in this trial if any of the following criteria apply.
  • Patients with the following medication or treatment history:
  • ① Donor lymphocyte infusion (DLI) within 4 weeks
  • Graft-versus-host-disease (GVHD) treatment within four weeks (In case of maintaining medication for post-treatment prophylaxis, the decision on the subject's participation in the clinical trial may be made after contacting and consulting with the Sponsor's Medical Monitor.)
  • Central nervous system (CNS) radiotherapy or intracerebrospinal antineoplastic therapy within eight weeks (However, intrathecal therapy for prophylaxis purposes is an exception) ④ Systemic salvage chemotherapy that includes TKI and blinatumomab for treatment of Philadelphia positive ALL within one week prior to Screening or five half-lives of the administered drug (whichever is shorter)
  • Any prior anti-CD19 treatment (with the exception of blinatumomab) ⑥ History of neurological toxicity ≥ Grade 4 or cytokine release syndrome (CRS) ≥ Grade 4 per CTCAE during prior anti-CD19 treatment
  • Patients with the following CNS abnormality:
  • ① CNS-3 disease, defined by WBC ≥ 5/μL in CSF and confirmed presence of lymphoblast, with or without neurological symptoms
  • ② CNS-3 disease, defined by WBC < 5/μL in CSF and confirmed presence of lymphoblast, with neurological symptoms (cases of CNS-1 disease without evidence of leukemia involvement in CSF and CNS-2 disease without neurological symptoms may be enrolled)
  • ③ Current or prior history of CNS disorder, such as epilepsy/seizure, cerebrovascular ischemia/bleeding, dementia, cerebellar disorder, autoimmune disease with CNS invasion, posterior reversible encephalopathy syndrome (PRES) or cerebral edema
  • Burkitt's lymphoma/leukemia per WHO Classification or chronic myelogenous leukemia lymphoid blast crisis
  • Primary immunodeficiency
  • Hereditary diseases (e.g., Fanconi anemia, Kostmann syndrome, and Shwachman-Diamond syndrome) or other bone marrow failure syndromes
  • 2. Common Exclusion Criteria
  • Subjects in Phase 1 study and Phase 2 study may not participate in this trial if any of the following criteria apply.
  • Patients with the following medical history:
  • History of malignancy with the following exceptions:
  • Basal cell or squamous cell skin cancer treated without relapse for at least three years prior to Screening
  • In-situ carcinoma of the cervix or breast treated without relapse for at least 3 years prior to Screening
  • Superficial bladder cancer treated without relapse for at least 3 years prior to Screening
  • A primary malignancy which has been completely resected and in complete remission for ≥ 5 years
  • Unstable angina and/or myocardial infarction within 12 months prior to Screening ③ Thromboembolic events, pulmonary embolism or bleeding diatheses within 6 months prior to Screening
  • Hypoxemia, clinically significant pleural effusion or clinically significant ECG findings within 6 months prior to Screening
  • Patients with the following concurrent disease at Screening:
  • Central nervous system (CNS) involvement by malignancy by magnetic resonance imaging (MRI) at Screening. However, for Cohort B, subjects with malignant tumor metastasis to the brain parenchyma confirmed by MRI scan.
  • Active infection with hepatitis B confirmed (HBsAg positive at Screening. But, in case of HBcAb IgG positive, the patient can be enrolled if he/she takes prophylactic anti-viral agent.)
  • Active infection with hepatitis C confirmed (HCV Ab tested positive at Screening. But, if screened negative for HCV RNA, the patient can be enrolled.) ④ Known human immunodeficiency virus (HIV) positive ⑤ Active neurological auto-immune or inflammatory disorder (e.g., Guillain Barre syndrome, amyotrophic lateral sclerosis) ⑥ Ventricular tachycardia and atrial fibrillation with rapid ventricular response not controlled (i.e., relapsed or symptomatic) with pharmacological treatment within three months prior to Screening
  • Showing rapid progression of study disease as per Investigator's discretion
  • Had major surgery requiring general anesthesia or mechanical ventilation within four weeks prior to Screening (for video-assisted thoracoscopic surgery (VATS) or open-and-closed (ONC) surgery, within two weeks prior to Screening)
  • Severe infection requiring anti-bacterial, anti-fungal or anti-viral medication or uncontrolled active infection at Screening
  • Use of other investigational medicinal products/devices within 4 weeks prior to Screening
  • Pregnant or lactating women
  • Hypersensitivity reaction to the ingredients of the Investigational Product
  • Other protocol-related inclusion/exclusion may apply.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Bom-I Kwon, BSc contact

+82428633698

bikwon@curocellbtx.com

Gunsoo Kim, MSc contact

gskim@curocellbtx.com

South Korea2 sites, 2 recruiting

  • Samsung Medical Center

    Seoul, 06351

    Wonseog Kim, MD, PhD, +821099335823, wonseog.kim@samsung.com

    Recruiting

  • The Catholic University of Korea Seoul St. Mary's Hospital

    Seoul, 06591

    Jae Ho Yoon, MD, PhD, 82-2-2258-6270, royoon@catholic.ac.kr

    Recruiting

Other trials in South Korea

About this study

Official title: An Open-label, Multi-center, Single-arm Phase 1/2 Study to Assess Tolerability, Safety and Efficacy of CRC01 in Adult Patients With Relapsed or Refractory Large B-cell Lymphoma and B-cell Acute Lymphoblastic Leukemia

This is a multi-center, phase I/II study to determine the efficacy and safety of CRC01 in adult patients with relapsed or refractory large B-cell lymphoma and B-cell Acute Lymphoblastic Leukemia.

Being tested
CRC01, Fludarabine, Cyclophosphamide
Keywords
CRC01, anti-CD19 CAR-T, CAR-T, CAR T cells, Chimeric antigen receptor, PD-1 knock down, TIGIT knock down
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.

  • CRC01Biological

    Cohort A :A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg.

    Cohort B :A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously at a target dose of 1.5 x 10^6 anti-CD19 CAR T cells/kg.

  • FludarabineDrug

    Administered according to package insert

  • CyclophosphamideDrug

    Administered according to package insert

Study groups in NCT04836507
Study groupRoleWhat they receive
CRC01ExperimentalA conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CRC01.
Receives: Biological: CRC01; Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

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

  1. Phase 1 Study: Maximum Tolerated Dose (MTD) which will be the Recommended Phase 2 Dose (RP2D)

    Measured: 28 days

  2. Phase 2 Pivotal Study: Cohort A : Overall Response Rate (ORR) Cohort B : Overall Complete Remission Rate (OCR)

    Cohort A : ORR is defined as the incidence of either a complete response (CR) or a partial response (PR) per the Lugano Criteria for Response Assessment (2014).

    Cohort B : OCR is defined as the incidence of either a complete Remission (CR) or a Complete Remission with incomplete hematologic recovery (CRi) per the ALL Response Criteria.

    Measured: 5 years

Secondary outcomes (12)

  1. Time to response (TTR)

    Measured: 5 years

  2. Duration of overall response (DOR)

    Measured: 5 years

  3. Event free survival (EFS)

    Measured: 5 years

  4. Progression free survival (PFS)

    Measured: 5 years

  5. Overall survival (OS)

    Measured: 5 years

  6. Incidence and severity of adverse events (AEs)

    Measured: 5 years

  7. Incidence of immunogenicity to CRC01

    Measured: 5 years

  8. Number of participants with presence of exposure to replication-competent lentivirus (RCL) as Assessed by quantitative polymerase chain reaction (qPCR)

    Measured: 5 years

  9. Incidence of secondary malignancy

    Measured: 5 years

  10. Peak concentration (Cmax) of CRC01 transduced cells into target tissues

    Measured: 5 years

  11. Area under the concentration versus time curve (AUC) of CRC01 transduced cells into target tissues

    Measured: 5 years

  12. Time to maximum observed concentration (Tmax) of CRC01 transduced cells into target tissues

    Measured: 5 years

Timeline

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

  1. First posted8 Apr 2021
  2. Study start2 Mar 2021
  3. Primary completion15 Aug 2030 (estimated)
  4. Study completion26 Sep 2030 (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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
91 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04836507
Sponsor's protocol ID
CRC01-01
Status last verified
Jun 2026
First submitted
5 Apr 2021
Last updated
1 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Kim WS, Kim SJ, Yoon DH, Cho H, Yoon SE, Yang DH, Shin HJ, Eom HS, Lee E, Byun JM, Koh Y, Lee H, Jung J, Yoon SS, Song GY, Kim DY, Hong J, Park Y, Han S, Cho SH. Anbalcabtagene autoleucel (PD-1 and TIGIT knockdown CD19 CAR-T) for relapsed/refractory large B-cell lymphoma (CRC01-01). Blood. 2026 Jun 12:blood.2025032636. doi: 10.1182/blood.2025032636. Online ahead of print.

    PubMed 42284198

  • Lee YH, Lee HJ, Kim HC, Lee Y, Nam SK, Hupperetz C, Ma JSY, Wang X, Singer O, Kim WS, Kim SJ, Koh Y, Jung I, Kim CH. PD-1 and TIGIT downregulation distinctly affect the effector and early memory phenotypes of CD19-targeting CAR T cells. Mol Ther. 2022 Feb 2;30(2):579-592. doi: 10.1016/j.ymthe.2021.10.004. Epub 2021 Oct 8.

    PubMed 34628052

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CRC01, Fludarabine and Cyclophosphamide in people with Relapsed Large B-cell Lymphoma and Refractory Large B-cell Lymphoma, run by Curocell Inc. at 2 sites in South Korea.

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 56 inclusion and 69 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: looking for participants now, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in South Korea. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Contact Bom-I Kwon, BSc (+82428633698, bikwon@curocellbtx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1 Study: Maximum Tolerated Dose (MTD) which will be the Recommended Phase 2 Dose (RP2D) (time frame: 28 days). 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 NCT04836507, which also lists 2 linked publications.

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 Jul 2026.

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