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

Trial details

Who runs it

British Columbia Cancer Agency

Trial code

NCT06208735

Record updated

14 October 2026

Original description

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.Read full original descriptionShow less

CLIC-02: A Phase I Trial of CLIC-2201 for the Treatment of Relapsed/Refractory B Cell Malignancies

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.

Inclusion: 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; 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:; Left ventricular ejection fraction (LVEF) ≥ 45%, and no current evidence of significant cardiac dysfunction; Creatinine clearance using Cockcroft-Gault of > 30 mL/min, AND; ALP/ALT < 5X upper limit of normal (ULN), conjugated bilirubin < 2X ULN, and no evidence or history of liver cirrhosis; Participants must have Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 or Karnofsky Score ≥50%; Females of child-bearing potential and sexually active males must agree to use a highly effective contraception method (see section 5.4) through to at least one year following administration of the CLIC-2201 product; Participants with accessible disease, must be willing to undergo a tumour biopsy at enrolment. For participants with a recent (within 3 months) tumor biopsy, access to the archival biopsy is acceptable; Participants in the cohort B must be between 1-39 years of age at the time of consent; For participants who are under the age of consent as defined by REB requirements, parent or legal guardian of the participant must provide the informed consent and the participant's assent/consent must be obtained (if applicable); Participants must have a relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL); 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 in cohort B and/or those who have received CD22 targeted therapy must have documentation of CD22 tumour expression within the 6 months prior to study screening, and after any prior CD22 directed therapy (if applicable); Participants must have adequate organ function at enrolment, defined as:; Left ventricular ejection fraction (LVEF) ≥ 45%, and no current evidence of significant cardiac dysfunction; Creatinine clearance using Cockcroft-Gault or Schwartz equation of > 30 mL/min, AND; ALP/ALT < 5X upper limit of normal (ULN), conjugated bilirubin < 2X ULN, and no evidence or history of liver cirrhosis; Participants must have a Karnofsky or Lansky Score ≥50%; Participants of reproductive age must agree to use a highly effective contraception method through to at least one year following administration of the CLIC-2201 product; Participants must be willing to undergo a bone marrow biopsy at enrolment.

Exclusion: Live vaccine ≤6 weeks prior to enrolment; Concomitant genetic syndrome associated with bone marrow failure such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure or immunodeficiency syndrome; Any uncontrolled or serious active infection at the time of enrolment; Active autoimmune disease requiring immunosuppressive therapy within 4 weeks of enrolment; Active Graft Versus Host Disease (GVHD) requiring systemic immunosuppressive therapy within 4 weeks of enrolment; 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; Active (confirmed by PCR) hepatitis B or hepatitis C at time of screening confirmed by PCR; Any Human Immunodeficiency Virus (HIV) infection at time of screening; Hypersensitivity to fludarabine or cyclophosphamide; Any allergy to gentamycin or its derivatives; 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, unless used as treatment for the B cell malignancy; 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; Diagnosis of primary central nervous system lymphoma (PCNSL); Participants who do not meet the minimum weight requirement for the planned dose level; Pregnant or nursing participants.

ClinicalTrials.gov NCT06208735