B-Cell LeukemiaPhase 1NCT06208735
CLIC-2201 for the Treatment of Relapsed/Refractory B Cell Malignancies
A Phase 1 study testing CLIC-2201 in people with B-Cell Leukemia and Non-Hodgkin's Lymphoma, run by British Columbia Cancer Agency at 7 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- B-Cell Leukemia, Non-Hodgkin's Lymphoma, B-cell Acute Lymphoblastic Leukemia
- What is being tested?
- CLIC-2201
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 7 sitesCanada
- Study dates
- 2 Jan 2025to 1 Aug 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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,
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- 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.
Who cannot join
- 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.
- Diagnosis of primary central nervous system lymphoma (PCNSL)
- Treatment with any of the following in the specified time period before leukapheresis:
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- 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.
- 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.
- 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.
- 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
- Participants who do not meet the minimum weight requirement for the planned dose level.
- Pregnant or nursing participants.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
Canada7 sites, 7 recruiting
- Recruiting
Arthur J.E. Child Comprehensive Cancer Centre
Calgary, Alberta, T2N 5G2
Karm Alhasan, karm.alhasan2@cancercarealberta.ca
Robert Puckrin, MD
- Recruiting
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
Sherry Qian, sherry.qian@albertahealthservices.ca
Victor Lewis, MD
- Recruiting
The Ottawa Hospital - General Campus
Ottawa, Ontario, K1H 8L6
Vanessa Lopez, vlopez@ohri.ca
Natasha Kekre, MD
- Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario
Hannah Sendzik, hannah.sendzik@uhn.ca
John Kuruvilla, MD
- Recruiting
The Hospital for Sick Children
Toronto, Ontario
Erilda Kapllani, erilda.kapllani@sickkids.ca
Joerg Krueger, MD
- Recruiting
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
Madeleine Cannings, madeleine.cannings@bccancer.bc.ca
Hannah Cherniawsky, MD
- Recruiting
BC Children's Hospital
Vancouver, British Columbia
Nima Molavi, nima.molavi@cw.bc.ca
Amanda Li, MD
About this study
Official title: 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.
Read more
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.
Read the detailed description
This is a Phase I, first-in-human, open-label multicenter trial of CLIC-2201 CAR-T cells for participants with relapsed/refractory B cell malignancies.
This trial will be conducted in two cohorts (cohort A, including 12 adult participants with B-NHL and cohort B, including 12 paediatric/young adult participants with B-ALL).
Consented participants will undergo a series of tests to confirm eligibility. Following eligibility confirmation, participants will undergo leukapheresis, which enables CLIC-2201 manufacturing. Leukapheresis is a procedure where white blood cells are collected from the blood. The collected cells will be shipped fresh to the Conconi Family Immunotherapy Laboratory (CFIL) in Victoria, BC, where manufacturing will take place.
At the CFIL lab, the autologous T cells will be selected, activated, and transduced with lentivirus to deliver the sdCD22 CAR transgene and then expanded over a period of 8 days in an automated, closed process on the CliniMACS Prodigy.
Participants will undergo lymphodepleting chemotherapy consisting of fludarabine (40 mg/m^2 daily x 3 days) and cyclophosphamide (500 mg/m^2 daily x 2 days) on trial days -4 and -3. The chemotherapy will deplete the exciting immune cells and give a chance to the infused CAR-T cells to expand and grow in the body.
Infusion of the autologous CLIC-2201 will follow at least 48 hours after but within seven days of completion of the last dose of fludarabine.
The standard 3+3 design will be used for CLIC-2201 administration to guide dosing and determination of the maximum tolerated dose (MTD). At each dose level, a decision will be made by the study team to escalate (E), stay at the current dose (S), de-escalate (D), or remove that dose level from further enrollment on trial (R) based on the number of dose-limiting toxicities (DLTs) evaluable participants who experience a DLT at that level.
There is no evidence that dosing of CAR-T cells/kg is different between paediatric and adult populations; however, most CAR-T cell products for B-ALL typically used a lower dose than for B-NHL. Therefore, in this trial, each dose level will be evaluated in adults before enrolling pediatric participants at that dose level.
Participants in each cohort will be enrolled and treated in groups of n=3. The first 3 participants (group 1) will be treated at DL1. The first participant at this dose level will be staggered for a minimum of 28 days to allow for the full assessment of DLTs. After this, the other two participants enrolled at this level will be monitored for a minimum 14-day period. The staggered intervals pattern will be repeated for each dose level.
If none of the three participants in group 1 experiences a DLT, another group of three participants will be treated at the next higher dose level (DL2).
If >=2/3 participants experience a DLT, the dose will be de-escalated to DL-1, with de-escalation to DL-1 potentially occurring if both first 2 participants experience a DLT.
If 1/3 participants experience a DLT, an additional group of 3 more participants will be treated at the same dose level.
The dose escalation will continue until the maximum dose level (DL3) is reached without significant DLTs, or when at least 2/6 participants experience DLTs at a certain dose level (i.e., 33% of patients with a DLT at that dose level). The MTD will then be defined as the dose level just below this toxic dose level.
To receive the CLIC-2201 infusion, participants will be admitted to the in-patient unit, and they will remain at the hospital for a minimum of 7 days to be monitored closely for any complication, infection, and side effects. The participants will be discharged to the appropriate outpatient clinic if they are deemed medically stable after this time.
Participants will be seen at the outpatient clinic or daycare unit on days 10, 14, 21, 28, 60, 90, 180, 365, 547, and 730 after the CLIC-2201 infusion. They will continue with annual follow-up visits up to 15 years post-CLIC-2201 infusion.
- Conditions
- B-Cell Leukemia, Non-Hodgkin's Lymphoma, B-cell Acute Lymphoblastic Leukemia, Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, Primary Mediastinal Large B-cell Lymphoma (PMBCL)
- Being tested
- CLIC-2201
- Keywords
- Chimeric Antigen Receptor T cells, CLIC-2201, CD22, Immunotherapy, CAR-T cell
- Medical subject headings
- Leukemia, B-Cell, Lymphoma, Non-Hodgkin, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CLIC-2201Biological
Also called Autologous CD22 targeting CAR-T cells
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.
| Study group | Role | What they receive |
|---|---|---|
| CLIC-2201 | Experimental | A single Intravenous infusion of CLIC-2201 will be given. Receives: Biological: CLIC-2201 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
This would be used to measure the anti-tumour activities of the CLIC-2201 treatment within a year after the infusion. The complete response will be assessed on days 28, 90, 180, and 365.
Response for lymphoma participants will be defined by Lugano criteria and for B-ALL participants by CIBMTR response criteria.
Measured: Within 730 days of CAR-T infusion
Proportion of participants with an overall response [achieving a CR or partial remission (PR)]
This would be used to measure the anti-tumour activities of the CLIC-2201 treatment within a year after the infusion.
Measured: Within 730 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.
This would be used to measure the anti-tumour activities of the CLIC-2201 treatment within a year after the infusion. The partial remission will be assessed on days 28, 90, 180, and 365.
Measured: Within 730 days of CAR-T infusion
Overall survival rate
This would be used to measure the the anti-tumor activities of the CLIC-2201 treatment within 6 months after the infusion.
Measured: Up to 15 years of CAR-T infusion
Progression free survival rate
This would be used to measure the the anti-tumor activities of the CLIC-2201 treatment within 6 months after the infusion.
Measured: Up to 15 years of CAR-T infusion
The average number of CAR transgene copies per cell
This would be used to evaluate the pharmacokinetics of the CLIC-2201 treatment.
Measured: Up to day 730
Proportion of participants who fail enrollment that were successfully screened
This would be used to evaluate the feasibility of administering CLIC-2201 cells to participants with relapsed/refractory B Cell Malignancies.
Measured: Enrollment
Proportion of participants for whom leukapheresis failed that successfully completed trial enrollment
This would be used to evaluate the feasibility of administering CLIC-2201 cells to participants with relapsed/refractory B Cell Malignancies.
Measured: From date of enrollment until the date of leukapheresis, assessed up to 4 weeks
Proportion of participants for whom CLIC-2201 manufacturing was unsuccessful that completed leukapheresis
This would be used to evaluate the feasibility of administering CLIC-2201 cells to participants with relapsed/refractory B Cell Malignancies.
Measured: Through manufacturing, an average of 8 days
Proportion of participants who fail to receive CLIC-2201 infusion for whom a CLIC-2201 was successfully manufactured
This would be used to evaluate the feasibility of administering CLIC-2201 cells to participants with relapsed/refractory B Cell Malignancies.
Measured: Day of CLIC-2201 infusion
Median time from enrollment to leukapheresis
This would be used to evaluate the feasibility of administering CLIC-2201 cells to participants with relapsed/refractory B Cell Malignancies.
Measured: From date of enrollment until the date of leukapheresis, assessed up to 4 weeks
Median time from enrollment to CLIC-2201 infusion
This would be used to evaluate the feasibility of administering CLIC-2201 cells to participants with relapsed/refractory B Cell Malignancies.
Measured: From date of enrollment until the date of infusion, assessed up to 6 weeks
Median time from enrollment to disease progression that prevents CLIC-2201 infusion.
This would be used to evaluate the feasibility of administering CLIC-2201 cells to participants with relapsed/refractory B Cell Malignancies.
Measured: From date of enrollment until the date of infusion, assessed up to 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2024
- Study start2 Jan 2025
- Primary completion1 Aug 2027 (estimated)
- Study completion1 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-Cell LeukemiaStudies of the same condition, open and under way.
- More trials run by British Columbia Cancer AgencyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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 1-39 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.
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- British Columbia Cancer Agency
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kevin Hay, MD, Principal investigator, BC Cancer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06208735
- Sponsor's protocol ID
- CLIC-02
- Status last verified
- Oct 2026
- First submitted
- 20 Dec 2023
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CLIC-02: A Phase I Trial of CLIC-2201 for the Treatment of Relapsed/Refractory B Cell Malignancies
- ClinicalTrials.gov ID
- NCT06208735
- Acronym / sponsor ID
- CLIC-02
- Conditions
- B-Cell Leukemia, Non-Hodgkin's Lymphoma, B-cell Acute Lymphoblastic Leukemia, Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, Primary Mediastinal Large B-cell Lymphoma (PMBCL)
- Keywords
- Chimeric Antigen Receptor T cells, CLIC-2201, CD22, Immunotherapy, CAR-T cell
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- British Columbia Cancer AgencyUniversity, hospital or other
- Study start
- 2 Jan 2025 (actual)
- Primary completion
- 1 Aug 2027 (estimated)
- Study completion
- 1 Aug 2028 (estimated)
- First posted
- 17 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase I, first-in-human, open-label multicenter trial of CLIC-2201 CAR-T cells for participants with relapsed/refractory B cell malignancies.
This trial will be conducted in two cohorts (cohort A, including 12 adult participants with B-NHL and cohort B, including 12 paediatric/young adult participants with B-ALL).
Consented participants will undergo a series of tests to confirm eligibility. Following eligibility confirmation, participants will undergo leukapheresis, which enables CLIC-2201 manufacturing. Leukapheresis is a procedure where white blood cells are collected from the blood. The collected cells will be shipped fresh to the Conconi Family Immunotherapy Laboratory (CFIL) in Victoria, BC, where manufacturing will take place.
At the CFIL lab, the autologous T cells will be selected, activated, and transduced with lentivirus to deliver the sdCD22 CAR transgene and then expanded over a period of 8 days in an automated, closed process on the CliniMACS Prodigy.
Participants will undergo lymphodepleting chemotherapy consisting of fludarabine (40 mg/m^2 daily x 3 days) and cyclophosphamide (500 mg/m^2 daily x 2 days) on trial days -4 and -3. The chemotherapy will deplete the exciting immune cells and give a chance to the infused CAR-T cells to expand and grow in the body.
Infusion of the autologous CLIC-2201 will follow at least 48 hours after but within seven days of completion of the last dose of fludarabine.
The standard 3+3 design will be used for CLIC-2201 administration to guide dosing and determination of the maximum tolerated dose (MTD). At each dose level, a decision will be made by the study team to escalate (E), stay at the current dose (S), de-escalate (D), or remove that dose level from further enrollment on trial (R) based on the number of dose-limiting toxicities (DLTs) evaluable participants who experience a DLT at that level.
There is no evidence that dosing of CAR-T cells/kg is different between paediatric and adult populations; however, most CAR-T cell products for B-ALL typically used a lower dose than for B-NHL. Therefore, in this trial, each dose level will be evaluated in adults before enrolling pediatric participants at that dose level.
Participants in each cohort will be enrolled and treated in groups of n=3. The first 3 participants (group 1) will be treated at DL1. The first participant at this dose level will be staggered for a minimum of 28 days to allow for the full assessment of DLTs. After this, the other two participants enrolled at this level will be monitored for a minimum 14-day period. The staggered intervals pattern will be repeated for each dose level.
If none of the three participants in group 1 experiences a DLT, another group of three participants will be treated at the next higher dose level (DL2).
If >=2/3 participants experience a DLT, the dose will be de-escalated to DL-1, with de-escalation to DL-1 potentially occurring if both first 2 participants experience a DLT.
If 1/3 participants experience a DLT, an additional group of 3 more participants will be treated at the same dose level.
The dose escalation will continue until the maximum dose level (DL3) is reached without significant DLTs, or when at least 2/6 participants experience DLTs at a certain dose level (i.e., 33% of patients with a DLT at that dose level). The MTD will then be defined as the dose level just below this toxic dose level.
To receive the CLIC-2201 infusion, participants will be admitted to the in-patient unit, and they will remain at the hospital for a minimum of 7 days to be monitored closely for any complication, infection, and side effects. The participants will be discharged to the appropriate outpatient clinic if they are deemed medically stable after this time.
Participants will be seen at the outpatient clinic or daycare unit on days 10, 14, 21, 28, 60, 90, 180, 365, 547, and 730 after the CLIC-2201 infusion. They will continue with annual follow-up visits up to 15 years post-CLIC-2201 infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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 1-39 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.
| Arm | Type | Receives |
|---|---|---|
| CLIC-2201 | Experimental | Biological: CLIC-2201A single Intravenous infusion of CLIC-2201 will be given. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (36 listed)
- 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:
- Participants must have refractory or relapsed disease, defined as one of the following:
- Participants must have adequate organ function at enrolment, defined as:
Key exclusion criteria (23 listed)
- 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.
- Diagnosis of primary central nervous system lymphoma (PCNSL)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CLIC-2201Also: Autologous CD22 targeting CAR-T cellsParticipants 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. | Biological | CLIC-2201 |
Primary outcome
Defining the maximum tolerated dose (MTD) of CLIC-2201
Time frame: Within the first 28 days of CAR-T infusion
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).
Proportion of participants who experienced any grade of CRS to define the safety of CLIC-2201
Time frame: Within the first 28 days of CAR-T infusion
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.
Proportion of participants who experienced any grade of ICANs to define the safety of CLIC-2201
Time frame: Within the first 28 days of CAR-T infusion
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.
Proportion of participants who experienced any grade of IEC-HS to define the safety of CLIC-2201
Time frame: Within the first 28 days of CAR-T infusion
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.
Proportion of participants who experienced any grade of AEs to define the safety of CLIC-2201
Time frame: Within the first 28 days of CAR-T infusion
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.
Proportion of participants who experienced any SAEs to define the safety of CLIC-2201
Time frame: Within the first 28 days of CAR-T infusion
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.
13 secondary outcomes
Proportion of participants achieving achieving and/or maintaining Complete response (CR) or complete response with incomplete count recovery (CRi).
Time frame: Within 730 days of CAR-T infusion
Proportion of participants with an overall response [achieving a CR or partial remission (PR)]
Time frame: Within 730 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.
Time frame: Within 730 days of CAR-T infusion
Overall survival rate
Time frame: Up to 15 years of CAR-T infusion
Progression free survival rate
Time frame: Up to 15 years of CAR-T infusion
The average number of CAR transgene copies per cell
Time frame: Up to day 730
Proportion of participants who fail enrollment that were successfully screened
Time frame: Enrollment
Proportion of participants for whom leukapheresis failed that successfully completed trial enrollment
Time frame: From date of enrollment until the date of leukapheresis, assessed up to 4 weeks
Proportion of participants for whom CLIC-2201 manufacturing was unsuccessful that completed leukapheresis
Time frame: Through manufacturing, an average of 8 days
Proportion of participants who fail to receive CLIC-2201 infusion for whom a CLIC-2201 was successfully manufactured
Time frame: Day of CLIC-2201 infusion
Median time from enrollment to leukapheresis
Time frame: From date of enrollment until the date of leukapheresis, assessed up to 4 weeks
Median time from enrollment to CLIC-2201 infusion
Time frame: From date of enrollment until the date of infusion, assessed up to 6 weeks
Median time from enrollment to disease progression that prevents CLIC-2201 infusion.
Time frame: From date of enrollment until the date of infusion, assessed up to 6 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kevin Hay, MD principal investigator
BC Cancer
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CLIC-2201 in people with B-Cell Leukemia and Non-Hodgkin's Lymphoma, run by British Columbia Cancer Agency at 7 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kevin Hay, MD ((403) 210-6191, kevin.hay@bccancer.bc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Defining the maximum tolerated dose (MTD) of CLIC-2201 (time frame: Within the first 28 days of CAR-T infusion). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2026.