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

April 29, 2021 updated by: Curocell Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

91

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. ≥ 19 years of age and provided written informed consent

  2. 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
  3. 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.
  4. At least one measurable lesion (Long diameter ≥ 1.5cm)
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

  6. 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

  7. 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/㎕

  8. 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
  9. Hemodynamically stable, without pericardial effusion and Left Ventricle Ejection Fraction (LVEF) ≥ 50% confirmed by Echocardiogram (ECG) or Multigated Radionuclide Angiography (MUGA)
  10. Must have an apheresis product of non-mobilized cells accepted for manufacturing
  11. Life expectancy ≥ 12 weeks
  12. 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

Exclusion Criteria:

  1. 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

  2. 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
  3. Rapidly progressing the disease as per investigator's discretion
  4. 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.)
  5. Severe infection requiring anti-bacterial, anti-fungal or anti-viral medication or uncontrolled active infection

  6. 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
  7. Eligible for and consenting to ASCT
  8. Use of investigational medicinal product/device within 4 weeks prior to screening
  9. Pregnant or lactating women
  10. Hypersensitivity reaction to the excipients of CRC01 cell product

  11. 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)

Other protocol-related inclusion/exclusion may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: CRC01
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, CRC01.
Drug: Cyclophosphamide
Administered according to package insert
Drug: Fludarabine
Administered according to package insert
Biological: CRC01
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1 Study: Maximum Tolerated Dose (MTD) which will be the Recommended Phase 2 Dose (RP2D)
Time Frame: 28 days
28 days
Phase 2 Pivotal Study: Overall Response Rate (ORR)
Time Frame: 5 years
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 Outcome Measures

Outcome Measure
Time Frame
Overall survival (OS)
Time Frame: 5 years
5 years
Progression free survival (PFS)
Time Frame: 5 years
5 years
Incidence and severity of adverse events (AEs)
Time Frame: 5 years
5 years
Time to response (TTR)
Time Frame: 5 years
5 years
Duration of overall response (DOR)
Time Frame: 5 years
5 years
Event free survival (EFS)
Time Frame: 5 years
5 years
Incidence of immunogenicity to CRC01
Time Frame: 5 years
5 years
Number of participants with presence of exposure to replication-competent lentivirus (RCL) as Assessed by quantitative polymerase chain reaction (qPCR)
Time Frame: 5 years
5 years
Incidence of secondary malignancy
Time Frame: 5 years
5 years
Peak concentration (Cmax) of CRC01 transduced cells into target tissues
Time Frame: 5 years
5 years
Area under the concentration versus time curve (AUC) of CRC01 transduced cells into target tissues
Time Frame: 5 years
5 years
Time to maximum observed concentration (Tmax) of CRC01 transduced cells into target tissues
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Curocell Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 2, 2021

Primary Completion (ANTICIPATED)

May 1, 2023

Study Completion (ANTICIPATED)

February 1, 2028

Study Registration Dates

First Submitted

April 5, 2021

First Submitted That Met QC Criteria

April 5, 2021

First Posted (ACTUAL)

April 8, 2021

Study Record Updates

Last Update Posted (ACTUAL)

May 3, 2021

Last Update Submitted That Met QC Criteria

April 29, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRC01-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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