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.
∙ 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) ≥40%,
⁃ 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%,
⁃ 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 (see section 5.4) 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.