NCT04836507

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
91

participants targeted

Target at P75+ for phase_1

Timeline
21mo left

Started Mar 2021

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress75%
Mar 2021Feb 2028

Study Start

First participant enrolled

March 2, 2021

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

April 5, 2021

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 8, 2021

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2023

Completed
4.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2028

Expected
Last Updated

May 3, 2021

Status Verified

April 1, 2021

Enrollment Period

2.2 years

First QC Date

April 5, 2021

Last Update Submit

April 29, 2021

Conditions

Relapsed Large B-cell LymphomaRefractory Large B-cell LymphomaDiffuse Large B-cell Lymphoma (DLBCL)Primary Mediastinal Large B-Cell Lymphoma (PMBCL)High-grade B-cell LymphomaTransformed Follicular Lymphoma (TFL)

Keywords

CRC01anti-CD19 CAR-TCAR-TCAR T cellsChimeric antigen receptorPD-1 knock downTIGIT knock down

Outcome Measures

Primary Outcomes (2)

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

    28 days

  • Phase 2 Pivotal Study: Overall Response Rate (ORR)

    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).

    5 years

Secondary Outcomes (12)

  • Time to response (TTR)

    5 years

  • Duration of overall response (DOR)

    5 years

  • Event free survival (EFS)

    5 years

  • Progression free survival (PFS)

    5 years

  • Overall survival (OS)

    5 years

  • +7 more secondary outcomes

Study Arms (1)

CRC01

EXPERIMENTAL

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CRC01.

Biological: CRC01Drug: FludarabineDrug: Cyclophosphamide

Interventions

CRC01BIOLOGICAL

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.

CRC01
FludarabineDRUG

Administered according to package insert

CRC01
CyclophosphamideDRUG

Administered according to package insert

CRC01

Eligibility Criteria

Age19 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥ 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
  • 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:
  • +11 more criteria

You may not qualify if:

  • 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
  • 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
  • +19 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Related Publications (1)

  • 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.

    PMID: 34628052DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

fludarabineCyclophosphamide

Condition Hierarchy (Ancestors)

Lymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Central Study Contacts

Bom-I Kwon, BSc

CONTACT

+82428633698bikwon@curocellbtx.com

Gunsoo Kim, MSc

CONTACT

gskim@curocellbtx.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 5, 2021

First Posted

April 8, 2021

Study Start

March 2, 2021

Primary Completion

May 1, 2023

Study Completion (Estimated)

February 1, 2028

Last Updated

May 3, 2021

Record last verified: 2021-04

Locations

KR(1)