A Modular, Phase I/II Study to Evaluate CT204V-CD19 x CD20 in Participants With Relapsed or Refractory B-Cell Malignancies. (CT204V)

A Modular, Phase I/II, Open-label, Single-arm, Multicenter, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Cellular Kinetics, Pharmacodynamics, and Efficacy of CT204V-CD19 × CD20, an In Vivo Lentiviral Vector Gene Therapy Generating Dual Targeting Anti-CD19/CD20 Chimeric Antigen Receptor (CAR)-T Cells in Participants With Relapsed or Refractory B-Cell Malignancies

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of CT204V-CD19 × CD20, a dual targeting in vivo gene therapy generating anti-CD19/CD20 CAR-T cells in participants with R/R B-cell malignancies.

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed or Refractory B-Cell Malignancies
• Intervention / Treatment: Drug: CT204V-CD19 × CD20

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Study Information Center; Phone Number: +1877-240-9479; Email: information.center@astrazeneca.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• * Participants must be at least 18 years of age.
• * Confirmed expression of CD19 and/or CD20.
• * Histologically confirmed and measurable disease for all disease subtypes.
• * ECOG performance status 0 or 1.
• * Adequate organ and bone marrow function.
• * Body weight of at least 45 kg.
• * Contraceptive/barrier requirement consistent with local regulations.
• * Capable of giving signed informed consent.

Exclusion Criteria:

• * History of malignancy unless disease-free for ≥ 3 years, with exceptions.
• * Active CNS involvement by malignancy.
• * History of cardiac lymphoma involvement.
• * Richter's transformation of CLL.
• * Ongoing or impending oncologic emergency.
• * Active uncontrolled bacterial, viral, or fungal infection.
• * Active hepatitis B or C.
• * Positive HIV test.
• * Positive HTLV-1/2 antibody test.
• * Ongoing non-hematologic toxicities from prior therapy.
• * History of any grade IEC-HS, Grade ≥ 3 CRS, or Grade ≥ 2 NT during prior CAR-T cell therapy.
• * History of allogeneic stem cell or solid organ transplantation.
• * Primary immunodeficiency disorder.
• * History of specific autoimmune diseases.
• * Significant neurological or psychiatric conditions.
• * Receipt of prior treatment containing VSV-G.
• * Receipt of certain therapies within specified washout periods.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CT204V-CD19 × CD20; Participants will receive CT204V-CD19 × CD20, an In Vivo Lentiviral Vector Gene Therapy, generating dual targeting anti-CD19/CD20 Chimeric Antigen Receptor (CAR)-T cells.	Drug: CT204V-CD19 × CD20; Experimental; Other Names: CT204V

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events(AEs)/Serious Adverse Events (SAEs), Phase 1 of the study.	Incidence and severity of Adverse Events(AEs)/Serious Adverse Events (SAEs), Phase 1 of the study.	Up to 15 years
Number of Dose-Limiting Toxicities (DLTs) events during dose escalation, Phase 1 of the study.	Incidence of Dose-Limiting Toxicities (DLTs) during dose escalation, Phase 1 of the study.	Up to 28 days.
Number of AEs leading to dose reduction, withdrawal, interruption, Phase 1 of the study.	Incidence of AEs leading to dose reduction, withdrawal, interruption, Phase 1 of the study.	Up to 1 year.
Number of AEs leading to death, Phase 1 of the study.	Incidence of AEs leading to death, Phase 1 of the study.	Up to 15 years
Number of AESI (adverse events of special interest), Phase 1 of the study.	Incidence of AESI (adverse events of special interest), Phase 1 of the study.	Up to 15 years
Objective Response Rate (Complete Response+Partial Response) per Lugano Classification, Phase 2 of the study.	To assess the efficacy based on ORR (CR+PR) events.	Up to 24 months.
Complete Response (CR) rate, Phase 2 of the study.	To assess the efficacy based on CR rate.	Up to 24 months.
Best Overall Response (BOR), Phase 2 of the study.	To assess the efficacy based on BOR rate.	Up to 24 months.
Duration of Response (DoR), Phase 2 of the study.	To assess the efficacy based on DoR rate.	Up to 24 months.
Duration of Complete Response (DoCR), Phase 2 of the study.	To assess the efficacy based on DoCR rate.	Up to 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (Complete Response+Partial Response) per Lugano Classification, Phase 1 of the study.	To evaluate the preliminary antitumor activity of CT204V. ORR (CR+PR) per Lugano Classification based on ORR, as assessed by the investigator.	Up to 24 months post-infusion.
Viral vector PK parameter AUClast, Phase 1 of the study.	Quantification of CT204V viral vector genomes (viral titer) in peripheral blood per PK parameter AUClast, as assessed by the investigator.	Up to 24 months post-infusion.
Cellular Kinetics (CK) of CT204V CAR transgene parameter AUC0-28/AUClast, Phase 1 of the study.	Quantification of CT204V CAR transgene levels in peripheral blood per CAR transgene PK parameter AUC0-28/AUClast, as assessed by the investigator.	Up to 24 months post-infusion.
Incidence of Anti-Drug Antibodies (ADA), Phase 1 of the study.	To evaluate the humoral immunogenicity of CT204V and its vector components based on incidence of humoral immunogenicity (ADA) against CT204V and/or vector components, as assessed by the investigator.	Up to 24 months post-infusion.
Frequency and severity of AEs/SAEs	To further characterize the safety of CT204V with selected prophylaxis regimen.	Up to 15 years
Complete Response (CR) rate, Phase 1 of the study.	To evaluate the preliminary antitumor activity of CT204V per CR rate, as assessed by the investigator.	Up to 24 months post-infusion.
Best Overall Response (BOR), Phase 1 of the study.	To evaluate the preliminary antitumor activity of CT204V based on BOR, as assessed by the investigator.	Up to 24 months post-infusion.
Duration of Response (DoR), Phase 1 of the study.	To evaluate the preliminary antitumor activity of CT204V based on DoR. as assessed by the investigator.	Up to 24 months post-infusion.
Duration of Complete Response (DoCR), Phase 1 of the study.	To evaluate the preliminary antitumor activity ofCT204V based on DoCR, as assessed by the investigator.	Up to 24 months post-infusion.
Viral vector PK parameter Cmax/Clast, Phase 1 of the study.	Quantification of CT204V viral vector genomes (viral titer) in peripheral blood per PK parameter Cmax/Clast, as assessed by the investigator.	Up to 24 months post-infusion.
Viral vector PK parameter Tmax/Tlast, Phase 1 of the study.	Quantification of CT204V viral vector genomes (viral titer) in peripheral blood per PK parameter Tmax/Tlast, as assessed by the investigator.	Up to 24 months post-infusion.
Cellular Kinetics (CK) of CT204V CAR transgene parameter Cmax/Clast, Phase 1 of the study.	Quantification of CT204V CAR transgene levels in peripheral blood per CAR transgene PK parameter Cmax/Clast, as assessed by the investigator.	Up to 24 months post-infusion.
Cellular Kinetics (CK) of CT204V CAR transgene parameter Tmax/Tlast, Phase 1 of the study.	Quantification of CT204V CAR transgene levels in peripheral blood per CAR transgene PK parameter Tmax/Tlast.	Up to 24 months post-infusion.
Quantification of CT204V viral vector genomes (viral titer) in peripheral blood, Phase 2 of the study.	Quantification of CT204V viral vector genomes (viral titer) in peripheral blood, central read, central read.	Up to 24 months post-infusion.
Quantification of CT204V CAR transgene levels (copies/μg gDNA) in peripheral blood, Phase 1 of the study.	Quantification of CT204V CAR transgene levels (copies/μg gDNA) in peripheral blood, as assessed by the investigator.	Up to 24 months post-infusion.
Cellular Kinetics (CK) of CT204V CAR transgene parameter AUC0-28/AUClast, Phase 2 of the study.	Quantification of CT204V CAR transgene levels in peripheral blood per CAR transgene PK parameter AUC0-28/AUClast, central read.	Up to 24 months post-infusion.
Incidence of Anti-Drug Antibodies (ADA), Phase 2 of the study.	To evaluate the humoral immunogenicity of CT204V and its vector components based on incidence of humoral immunogenicity (ADA) against CT204V and/or vector components, central read.	Up to 24 months post-infusion.
Complete Response (CR) rate, Phase 2 of the study.	To evaluate the preliminary antitumor activity of CT204V per CR rate, central read.	Up to 24 months post-infusion.
Best Overall Response (BOR), Phase 2 of the study.	To evaluate the preliminary antitumor activity of CT204V based on BOR, central read.	Up to 24 months post-infusion.
Duration of Response (DoR), Phase 2 of the study.	To evaluate the preliminary antitumor activity of CT204V based on DoR, central read.	Up to 24 months post-infusion.
Duration of Complete Response (DoCR), Phase 2 of the study.	To evaluate the preliminary antitumor activity ofCT204V based on DoCR, central read.	Up to 24 months post-infusion.
Viral vector PK parameter Cmax/Clast, Phase 2 of the study.	Quantification of CT204V viral vector genomes (viral titer) in peripheral blood per PK parameter Cmax/Clast, central read.	Up to 24 months post-infusion.
Viral vector PK parameter Tmax/Tlast, Phase 2 of the study.	Quantification of CT204V viral vector genomes (viral titer) in peripheral blood per PK parameter Tmax/Tlast, central read.	Up to 24 months post-infusion.
Cellular Kinetics (CK) of CT204V CAR transgene parameter Cmax/Clast, Phase 2 of the study.	Quantification of CT204V CAR transgene levels in peripheral blood per CAR, transgene PK parameter Cmax/Clast, central read	Up to 24 months post-infusion.
Cellular Kinetics (CK) of CT204V CAR transgene parameter Tmax/Tlast, Phase 2 of the study.	Quantification of CT204V viral vector genomes (viral titer) in peripheral blood, central read, central read.	Up to 24 months post-infusion.
Viral vector PK parameter AUClast, Phase 2 of the study.	Quantification of CT204V viral vector genomes (viral titer) in peripheral blood per PK parameter AUClast, central read.	Up to 24 months post-infusion.
Objective Response Rate (Complete Response+Partial Response) per Lugano Classification, Phase 2 of the study.	To evaluate the preliminary antitumor activity of CT204V. ORR (CR+PR) per Lugano Classification based on ORR, central read.	Up to 24 months post-infusion.
Quantification of CT204V CAR transgene levels (copies/μg gDNA) in peripheral blood, Phase 2 of the study.	Quantification of CT204V CAR transgene levels (copies/μg gDNA) in peripheral blood, central read.	Up to 24 months post-infusion.
Quantification of CT204V viral vector genomes (viral titer) in peripheral blood, Phase 1 of the study.	Quantification of CT204V viral vector genomes (viral titer) in peripheral blood, central read, as assessed by the investigator.	Up to 24 months post-infusion.

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Estimated): November 9, 2026
• Primary Completion (Estimated): October 15, 2029
• Study Completion (Estimated): October 15, 2029

Study Registration Dates

• First Submitted: November 6, 2026
• First Submitted That Met QC Criteria: November 6, 2026
• First Posted (Actual): November 12, 2026

Study Record Updates

• Last Update Posted (Actual): November 12, 2026
• Last Update Submitted That Met QC Criteria: November 6, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Keywords: Gene Therapy; CAR-T; Phase I/II; B-Cell Malignancies; CT204V-CD19 x CD20
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Recurrence
• Other Study ID Numbers: R1055C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No