CLIC-2201 for the Treatment of Relapsed/Refractory B Cell Malignancies

NCT06208735 | Recruiting Phase 1 DMC

• 1 other identifier: CLIC-02
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 7

Brief Summary

This is a phase I dose-finding trial of an autologous CD22 targeting chimeric antigen receptor (CAR)-T cell product, called CLIC-2201, for participants with relapsed/refractory B cell malignancies. In the proposed trial, eligible enrolled participants will undergo leukapheresis for autologous T cell collection to enable CLIC-2201 manufacturing, followed by lymphodepletion with cyclophosphamide and fludarabine, then intravenous infusion of the autologous CLIC-2201 product. The trial will use the 3+3 design to escalate or de-escalate the dose level of CLIC-2201 administered. Participants will be monitored for safety and tolerability up to day 365 following CLIC-2201 infusion. The primary objective is to evaluate the safety and tolerability of CLIC-2201 and estimate the maximum tolerated dose (MTD) of CLIC-2201 in B-cell malignancies. The secondary objectives are to evaluate the (i) feasibility; (ii) anti-tumour activity of CLIC-2201; (iii) and characterize the pharmacokinetic (PK) profile of CLIC-2201. Exploratory objectives will include: i) characterizing the cellular and humoral immune responses against CLIC-2201 up to 1 year following infusion of CLIC-2201; (ii) characterizing the phenotype and gene expression profile of CLIC-2201 cells; (iii) evaluating immune and tumour cells at baseline and relapse for biomarkers of response or toxicity; (iv) evaluating serum cytokines, circulating tumour DNA (ctDNA) and B cell aplasia as biomarkers of clinical outcomes; and (v) assessing the quality of life.

Conditions

B-cell Acute Lymphoblastic Leukemia; Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma; Primary Mediastinal Large B-cell Lymphoma (PMBCL); Mantle Cell Lymphoma; B-cell Lymphoma; B-Cell Leukemia; Non-Hodgkin's Lymphoma

Keywords

Chimeric Antigen Receptor T cells; CLIC-2201; CD22; Immunotherapy; CAR-T cell

Outcome Measures

Primary Outcomes (6)

• Defining the maximum tolerated dose (MTD) of CLIC-2201

  The MTD will be measured by monitoring and recording the AEs experienced by the participant within the first 28 days after the infusion, including the treatment-related death as deemed by the investigator, grade 3 Cytokine Release Syndrome (CRS), Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS), and Immune Effector Cell-Associated Hemophagocytic Lymphocytosis-Like Syndrome (IEC-HS) lasting for more than seven days; grade 4 CRS, ICANS, and IEC-HS; grade 4 non-hematologic toxicity that is not deemed related to CRS, ICANS, IEC-HS (except for Grade 4 transaminases and isolated, asymptomatic laboratory electrolyte abnormalities for seven days or more).

  Within the first 28 days of CAR-T infusion

• Proportion of participants who experienced any grade of CRS to define the safety of CLIC-2201

  The safety will be measured by the proportion of participants who experienced any grade of CRS, ICANS, IEC-HS, any adverse events, and any severe adverse events.

  Within the first 28 days of CAR-T infusion

• Proportion of participants who experienced any grade of ICANs to define the safety of CLIC-2201

  The safety will be measured by the proportion of participants who experienced any grade of CRS, any grade of ICANS, any adverse events, and any severe adverse events.

  Within the first 28 days of CAR-T infusion

• Proportion of participants who experienced any grade of IEC-HS to define the safety of CLIC-2201

  The safety will be measured by the proportion of participants who experienced any grade of CRS, any grade of ICANS, any adverse events, and any severe adverse events.

  Within the first 28 days of CAR-T infusion

• Proportion of participants who experienced any grade of AEs to define the safety of CLIC-2201

  The safety will be measured by the proportion of participants who experienced any grade of CRS, any grade of ICANS, any adverse events, and any severe adverse events.

  Within the first 28 days of CAR-T infusion

• Proportion of participants who experienced any SAEs to define the safety of CLIC-2201

  The safety will be measured by the proportion of participants who experienced any grade of CRS, any grade of ICANS, any adverse events, and any severe adverse events.

  Within the first 28 days of CAR-T infusion

Secondary Outcomes (13)

• Proportion of participants achieving achieving and/or maintaining Complete response (CR) or complete response with incomplete count recovery (CRi).

  Within 365 days of CAR-T infusion

• Proportion of participants with an overall response [achieving a CR or partial remission (PR)]

  Within 365 days of CAR-T infusion

• Proportion of B-ALL participants with B with minimal residual disease (MRD) negative status by next-generation sequencing and/or high-resolution flow cytometry.

  Within 365 days of CAR-T infusion

• Overall survival rate

  Up to 15 years of CAR-T infusion

• Progression free survival rate

  Up to 15 years of CAR-T infusion

Other Outcomes (11)

• Serum cytokine levels before and after CAR-T cell infusion (Mesoscale)

  Up to day 28 after the infusion

• Proportion of participants with B-cell aplasia assessed by flow cytometry (BTNK panel)

  Within 365 days after the infusion

• Measurement (quantitative and qualitative) of circulating tumour DNA in peripheral blood.

  Within 365 days after the infusion

Study Arms (1)

CLIC-2201

EXPERIMENTAL

A single Intravenous infusion of CLIC-2201 will be given.

Biological: CLIC-2201

Interventions

CLIC-2201 BIOLOGICAL

Participants will undergo (a) lymphodepletion with cyclophosphamide and fludarabine, followed by (b) infusion of autologous CLIC-2201 CAR-T cells. All treatments will be delivered intravenously.

Also known as: Autologous CD22 targeting CAR-T cells

CLIC-2201

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet the following criteria to be enrolled on the trial:
• Participants in the cohort A must be 18 years of age or older of age at time of informed consent.
• Participants must provide written informed consent. The investigator is responsible for obtaining written informed assent/consent for the subject after adequate explanation of the study design, anticipated benefits and the potential risks. Subjects should sign the most current REB approved assent/consent prior to any study specific activity or procedure is performed. (Sites will follow their REB board requirements for consenting).
• Participants must have a relapsed or refractory B cell lymphoma, including one of the following:
• diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS),
• high grade B cell lymphoma NOS,
• high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements,
• primary mediastinal large B-cell lymphoma (PMBCL),
• aggressive B cell lymphoma transformed from an indolent lymphoma,
• mantle cell lymphoma (MCL),
• Participants must have refractory or relapsed disease, defined as one of the following:
• Relapse or refractory disease after at least 2 lines of therapy, OR
• Any relapse after autologous or allogeneic hematopoietic cell transplantation (HCT), OR
• Any relapse after CAR-T cell therapy.
• Participants must have adequate organ function at enrolment, defined as:

You may not qualify if:

• Any uncontrolled or serious active infection at the time of enrolment.
• Active autoimmune disease requiring immunosuppressive therapy within 4 weeks of enrolment.
• Live vaccine ≤6 weeks prior to enrolment
• Active Graft Versus Host Disease (GVHD) requiring systemic immunosuppressive therapy within 4 weeks of enrolment.
• Treatment with any of the following in the specified time period before leukapheresis:
• Allogeneic HCT within 3 months,
• Autologous HCT within 3 months,
• CD19 CAR-T cell infusion within 3 months,
• Donor lymphocyte infusion (DLI) within 3 months,
• Bendamustine within the last 6 months,
• Any investigational agent within 30 days or 5 half-lives (whichever is shorter),
• Systemic administration of therapeutic dose corticosteroids (\>20 mg/day prednisone or equivalent for adults and ≥ 12 mg/m2/day for paediatric participants) within 7 days prior to leukapheresis.
• Immunosuppressive therapies (i.e., calcineurin inhibitors, methotrexate, mycophenolate, rapamycin) within 4 weeks.
• Oral chemotherapy agents (i.e., venetoclax) within 5 half-lives. An exception to this is that bruton tyrosine kinase (BTK) inhibitors like ibrutinib can be continued in participants with mantle cell lymphoma throughout the trial period.
• Other concurrent malignancy or a prior malignancy treated within the past 2 years, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease.

Sponsors & Collaborators

• British Columbia Cancer Agency: lead

Study Sites (7)

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

RECRUITING

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

BC Children's Hospital

Vancouver, British Columbia, Canada

RECRUITING

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

RECRUITING

The Hospital for Sick Children

Toronto, Ontario, Canada

RECRUITING

MeSH Terms

Conditions

Leukemia, B-Cell; Lymphoma, Non-Hodgkin; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Study Officials

• Kevin Hay, MD

  BC Cancer

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kevin Hay, MD

CONTACT

(403) 210-6191; kevin.hay@bccancer.bc.ca

Narsis Afghari, MSc

CONTACT

(604) 675-4100; narsis.afghari@bccancer.bc.ca

Study Design

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

Model Details: This is a Phase I, first-in-human, open-label multicenter trial of CLIC-2201 CAR-T cells in participants with relapsed or refractory CD22-positive B-cell malignancies. The trial will consist of a 3+3 dose-escalation/de-escalation method in both cohorts (Cohort A: individuals who are 18 years or older and diagnosed with relapsed or refractory B-NHL and Cohort B: pediatric individuals who are 1-21 years old and diagnosed with relapsed or refractory B-ALL) to evaluate the safety and tolerability of increasing dose levels of CLIC-2201 in order to estimate the MTD.

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: January 17, 2024
• Study Start: January 2, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

CA (7)