NCT06208735 CLIC-2201 for the Treatment of Relapsed/Refractory B Cell Malignancies

Eligibility & Interventions

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What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

Phase 1 is the earliest stage of human testing — safety and dosage are the primary focus. Visits are frequent and medical supervision is intensive. You will be among the first people to receive this treatment.

This trial targets 24 participants in total. It began in 2025-01-02 with a primary completion date of 2027-08-01.

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.

Eligibility Criteria

Inclusion Criteria in Cohort A: Participants must meet the following criteria to be enrolled on the trial: 1. Participants in the cohort A must be 18 years of age or older of age at time of informed consent. 2. Participants must provide written informed consent. 3. Participants must have a relapsed or refractory B cell lymphoma, including one of the following: 1. diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), 2. high grade B cell lymphoma NOS, 3. high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, 4. primary mediastinal large B-cell lymphoma (PMBCL), 5. aggressive B cell lymphoma transformed from an indolent lymphoma, 6. mantle cell lymphoma (MCL), 4. Participants must have refractory or relapsed disease, defined as one of the following: 1. Relapse or refractory disease after at least 2 lines of therapy, OR 2. Any relapse after autologous or allogeneic hematopoietic cell transplantation (HCT), OR 3. Any relapse after CAR-T cell therapy. 5. Participants must have adequate organ function at enrolment, defined as: 1. Left ventricular ejection fraction (LVEF) ≥ 45%, and no current evidence of significant cardiac dysfunction. 2. Creatinine clearance using Cockcroft-Gault of \> 30 mL/min, AND 3. ALP/ALT \< 5X upper limit of normal (ULN), conjugated bilirubin \< 2X ULN, and no evidence or history of liver cirrhosis. 6. Participants must have Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 or Karnofsky Score ≥50%. 7. 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. 8. 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. Inclusion Criteria in Cohort B: 1. Participants in the cohort B must be between 1-39 years of age at the time of consent. 2. 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). 3. Participants must have a relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL). 4. Participants must have refractory or relapsed disease, defined as one of the following: 1. Relapse or refractory disease after at least 2 lines of therapy, OR 2. Any relapse after autologous or allogeneic hematopoietic cell transplantation (HCT), OR 3. Any relapse after CAR-T cell therapy. 5. 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). 6. Participants must have adequate organ function at enrolment, defined as: 1. Left ventricular ejection fraction (LVEF) ≥ 45%, and no current evidence of significant cardiac dysfunction. 2. Creatinine clearance using Cockcroft-Gault or Schwartz equation of \> 30 mL/min, AND 3. ALP/ALT \< 5X upper limit of normal (ULN), conjugated bilirubin \< 2X ULN, and no evidence or history of liver cirrhosis. 7. Participants must have a Karnofsky or Lansky Score ≥50%. 8. 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. 9. Participants must be willing to undergo a bone marrow biopsy at enrolment. Exclusion Criteria: 1. Any uncontrolled or serious active infection at the time of enrolment. 2. Active autoimmune disease requiring immunosuppressive therapy within 4 weeks of enrolment. 3. Live vaccine ≤6 weeks prior to enrolment 4. Active Graft Versus Host Disease (GVHD) requiring systemic immunosuppressive therapy within 4 weeks of enrolment. 5. Diagnosis of primary central nervous system lymphoma (PCNSL) 6. Treatment with any of the following in the specified time period before leukapheresis: 1. Allogeneic HCT within 3 months, 2. Autologous HCT within 3 months, 3. CD19 CAR-T cell infusion within 3 months, 4. Donor lymphocyte infusion (DLI) within 3 months, 5. Bendamustine within the last 6 months, 6. Any investigational agent within 30 days or 5 half-lives (whichever is shorter), 7. 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. 8. Immunosuppressive therapies (i.e., calcineurin inhibitors, methotrexate, mycophenolate, rapamycin) within 4 weeks, unless used as treatment for the B cell malignancy. 9. 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. 7. 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. 8. 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. 9. Active (confirmed by PCR) hepatitis B or hepatitis C at time of screening confirmed by PCR. 10. Any Human Immunodeficiency Virus (HIV) infection at time of screening. 11. Hypersensitivity to fludarabine or cyclophosphamide. 12. Any allergy to gentamycin or its derivatives 13. Participants who do not meet the minimum weight requirement for the planned dose level. 14. Pregnant or nursing participants.

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