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

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 ofinformed consent.

2. Participants must provide written informed consent. The investigator is responsiblefor obtaining written informed assent/consent for the subject after adequateexplanation of the study design, anticipated benefits and the potential risks.Subjects should sign the most current REB approved assent/consent prior to any studyspecific activity or procedure is performed. (Sites will follow their REB boardrequirements for consenting).

3. Participants must have a relapsed or refractory B cell lymphoma, including one ofthe following:

4. diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS),

5. high grade B cell lymphoma NOS,

6. high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements,

7. primary mediastinal large B-cell lymphoma (PMBCL),

8. aggressive B cell lymphoma transformed from an indolent lymphoma,

9. mantle cell lymphoma (MCL),

10. Participants must have refractory or relapsed disease, defined as one of thefollowing:

11. Relapse or refractory disease after at least 2 lines of therapy, OR

12. Any relapse after autologous or allogeneic hematopoietic cell transplantation (HCT), OR

13. Any relapse after CAR-T cell therapy.

14. Participants must have adequate organ function at enrolment, defined as:

15. Left ventricular ejection fraction (LVEF) ≥40%,

16. Creatinine clearance using Cockcroft-Gault of > 30 mL/min, AND

17. ALP/ALT < 5X upper limit of normal (ULN), conjugated bilirubin < 2X ULN, and noevidence or history of liver cirrhosis.

18. Participants must have Eastern Cooperative Oncology Group (ECOG) performance statusof ≤ 2 or Karnofsky Score ≥50%.

19. Females of child-bearing potential and sexually active males must agree to use ahighly effective contraception method (see section 5.4) through to at least one yearfollowing administration of the CLIC-2201 product.

20. Participants with accessible disease, willingness to undergo a tumour biopsy atenrolment. For participants with a recent (within 3 months) tumor biopsy, access tothe archival biopsy is acceptable.

Inclusion Criteria in Cohort B:

1. Participants in the cohort B must be between 1-21 years of age at the time ofconsent.

2. Parent or legal guardian of the participant signed the informed consent and theparticipant's assent/consent is obtained (if applicable). The investigator isresponsible for obtaining written informed assent/consent for the subject or legallyacceptable representative (e.g. parent, legal guardian) after adequate explanationof the study design, anticipated benefits and the potential risks. Subjects shouldsign the most current REB approved assent/consent prior to any study specificactivity or procedure is performed. (Sites will follow their REB board requirementsfor consenting).

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 thefollowing:

5. Relapse or refractory disease after at least 2 lines of therapy, OR

6. Any relapse after autologous or allogeneic hematopoietic cell transplantation (HCT), OR

7. Any relapse after CAR-T cell therapy.

8. Participants in cohort B and/or those who have received CD22 targeted therapy musthave documentation of CD22 tumour expression within the 6 months prior to studyscreening, and after any prior CD22 directed therapy (if applicable).

9. Participants must have adequate organ function at enrolment, defined as:

10. Left ventricular ejection fraction (LVEF) ≥45%,

11. Creatinine clearance using Cockcroft-Gault or Schwartz equation of > 30 mL/min,AND

12. ALP/ALT < 5X upper limit of normal (ULN), conjugated bilirubin < 2X ULN, and noevidence or history of liver cirrhosis.

13. Participants must have a Karnofsky or Lansky Score ≥50%.

14. Participants in reproductive age must agree to use a highly effective contraceptionmethod (see section 5.4) through to at least one year following administration ofthe CLIC-2201 product.

15. Participants willingness 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 ofenrolment.

3. Live vaccine ≤6 weeks prior to enrolment

4. Active Graft Versus Host Disease (GVHD) requiring systemic immunosuppressive therapywithin 4 weeks of enrolment.

5. Treatment with any of the following in the specified time period beforeleukapheresis:

6. Allogeneic HCT within 3 months,

7. Autologous HCT within 3 months,

8. CD19 CAR-T cell infusion within 3 months,

9. Donor lymphocyte infusion (DLI) within 3 months,

10. Bendamustine within the last 6 months,

11. Any investigational agent within 30 days or 5 half-lives (whichever isshorter),

12. Systemic administration of therapeutic dose corticosteroids (>20 mg/dayprednisone or equivalent for adults and ≥ 12 mg/m2/day for paediatricparticipants) within 7 days prior to leukapheresis.

13. Immunosuppressive therapies (i.e., calcineurin inhibitors, methotrexate,mycophenolate, rapamycin) within 4 weeks.

14. Oral chemotherapy agents (i.e., venetoclax) within 5 half-lives. An exceptionto this is that bruton tyrosine kinase (BTK) inhibitors like ibrutinib can becontinued in participants with mantle cell lymphoma throughout the trialperiod.

15. 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 withno evidence of active disease.

16. Concomitant genetic syndrome associated with bone marrow failure such as Fanconianemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failureor immunodeficiency syndrome.

17. Active (confirmed by PCR) hepatitis B or hepatitis C at time of screening confirmedby PCR.

18. Any Human Immunodeficiency Virus (HIV) infection at time of screening.

19. Hypersensitivity to fludarabine or cyclophosphamide.

20. Any allergy to gentamycin or its derivatives

21. Pregnant or nursing participants.