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

Prior treatment

• 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.

Other illness

• 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

Lab values

• 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.

Other

• 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.

• 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.