CLIC-1901 CART for Acute lymphoblastic leukaemia (B-ALL)|B-cell non-Hodgkin lymphoma (including diffuse large B-cell lymphoma, Burkitt lymphoma, mantle cell lymphoma, follicular lymphoma)|Chronic lymphocytic leukaemia (CLL)/Small lymphocytic lymphoma (SLL)

Inclusion criteria

• {"criterion_text":"- 1.\tRelapsed/refractory hematologic disease (in peripheral blood, bone marrow or lymph node biopsy by flow cytometry) defined as one of the following: a.\tCD19 expressing B-cell acute lymphoblastic leukemia (B-ALL) with one of the following: • First VHR relapse (very early relapse (<18 months from initial diagnosis of ALL or very high risk genetic features ((KMT2A-AFF1, E2A/TCF3-PBX1 rearrangements, hypodiploidy, TP53 alterations) • NCI HR and MRD ≥0.01% at end of consolidation according to the ALLTogether protocol •\tSecond or greater bone marrow (BM) relapse. •\tAny relapse after allogeneic haematopoietic stem cell transplantation (HSCT). •\tPrimary refractory, defined as not achieving complete remission (CR) after 2 cycles of standard chemotherapy regimen, or chemo refractory, defined as not achieving CR after 1 cycle of standard chemotherapy for relapsed leukemia. •\tPhiladelphia chromosome-positive ALL intolerant of or with 2 failed lines of tyrosine kinase inhibitor (TKI) therapy or if TKI therapy is contraindicated. •\tIneligible for allogeneic HSCT due to comorbidity, contraindications to conditioning regimen, lack of a suitable donor, prior HSCT, or declined allogeneic HSCT after documented detailed discussion of this treatment option with the given patient. b.\tHistologically confirmed B-cell non-Hodgkin’s lymphoma including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, High-grade B cell lymphoma with or without double hit, precursor B-cell lymphoblastic lymphoma (B-LBL), primary mediastinal large B-cell lymphoma, mantle cell lymphoma, Richter-transformed chronic lymphocytic lymphoma (CLL) or transformed follicular lymphoma with one of the following: •\tSecond or greater relapse. •\tRelapse after autologous or allogeneic haematopoietic stem cell transplantation (HSCT). •\tPrimary refractory, defined as not achieving at least partiel remission (PR) at time of end of treatment scanning or as defined in frontline protocol. b. Follicular lymphoma (FL) with both of the following: • ≥2 prior lines of therapy that included both an anti-CD20 antibody and an alkylating agent. • Histologically confirmed by a pathology review to have FL (grade 1, 2 or 3A), and no evidence of histologic transformation or FL grade 3B. c. Chronic lymphocytic lymphoma (CLL) and small lymphocytic lymphoma (SLL) with both of the following: • ≥2 prior lines of therapy that included Bruton tyrosine kinase inhibitors • No evidence of active CNS involvement."}
• {"criterion_text":"- 2.\tAge of 1-75 years"}
• {"criterion_text":"- 3.\tLife expectancy ≥ 12 weeks after enrollment"}
• {"criterion_text":"- 4.\tAdequate organ function defined as: a.\tLansky (<16 years) or Karnofsky (>16 years) score > 50% b.\tFEV1 or DLCOc ≥ 40 % of expected and oxygen saturation > 90% without oxygen supply c.\tLVEF > 45% and no symptoms of ischemic heart disease d.\tBilirubin < 2 x upper normal limit for age (except for patient diagnosed with Gilbert syndrome) e.\tALT < 5 x upper normal limit for age f.\tEDTA clearance >40mL/min (adults) or >30% of normal limit for age (children)"}
• {"criterion_text":"- 5.\tSigned statement of consent after receiving oral and written study information"}
• {"criterion_text":"- 6.\tAgreement to utilize highly effective contraception methods from time of leukapheresis until a minimum of 12 months after CAR-T infusion for all female patients of childbearing potential and all male patients with a female partner of childbearing potential. Highly effective contraception is defined as: total abstinence, female sterilization (oophorectomy, total hysterectomy or tubal ligation), male sterilization or use of oral, injected or implanted hormonal methods of contraception or placement or an intrauterine system/device."}

Exclusion criteria

• {"criterion_text":"- Prior malignancy (except for non-melanoma skin cancer) with on-going evidence of active disease or expected 5-year survival below 50% (as best estimation by treating oncologist)"}
• {"criterion_text":"- Patients with concomitant genetic syndrome, such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known familial bone marrow failure syndrome"}
• {"criterion_text":"- Prior treatment with any gene therapy product"}
• {"criterion_text":"- Treatment with any investigational agent within 30 days prior to enrollment"}
• {"criterion_text":"- Treatment with allogeneic haematopoietic stem cell transplantation within 6 months or donor lymphocyte infusion within 6 weeks from CAR-T infusion"}
• {"criterion_text":"- Acute or chronic graft-versus-host disease with the need for systemic corticosteroid treatment within 4 weeks prior to enrollment"}
• {"criterion_text":"- Acute or chronic infections with HIV"}
• {"criterion_text":"- Active infection with, hepatitis B or hepatitis C"}
• {"criterion_text":"- Active severe bacterial, viral or fungal infection"}
• {"criterion_text":"- Active Central Nervous System (CNS) involvement by malignancy, defined by CNS-3 per NCCN guidelines for ALL, or any evidence of lymphoma on lumbar puncture or brain imaging (if performed)."}
• {"criterion_text":"- Pre-existing significant central neurological disorder defined as CTCAE grade 3-4 (other than CNS involvement of underlying hematological malignancy)"}
• {"criterion_text":"- History of anaphylaxis to gentamicin or its derivates"}
• {"criterion_text":"- Pregnant or breastfeeding women"}

Primary endpoints

• {"endpoint_text":"- CRS: registration according to international grading system[31]. Endpoints include proportion of patients experiencing CRS of all grades and CRS grade 3-4","definition_or_measurement_approach":"CRS graded according to international grading system; measured as proportion of patients experiencing CRS (all grades) and CRS grade 3-4"}
• {"endpoint_text":"- ICANS: registration according to international grading system[31]. Endpoints include proportion of patients experiencing ICANS of all grades and ICANS grade 3-4.","definition_or_measurement_approach":"ICANS graded according to international grading system; measured as proportion of patients experiencing ICANS (all grades) and ICANS grade 3-4"}
• {"endpoint_text":"- Treatment with tocilizumab and/or glucocorticoids for CRS/ICANS.","definition_or_measurement_approach":"Recorded incidence of treatment with tocilizumab and/or glucocorticoids for management of CRS/ICANS"}
• {"endpoint_text":"- Cytopenia, including ICAHT grade ≥3 at day +28 and time to reach acceptable levels of neutrophils (≥1,.0 in three consecutive days), thrombocytes (≥100 in three consecutive days) and hemoglobin after CAR T-cell infusion.","definition_or_measurement_approach":"Cytopenias graded (ICAHT grade ≥3) at day +28 and time to blood count recovery defined by specified thresholds for neutrophils, platelets and hemoglobin"}
• {"endpoint_text":"- Episodes of neutropenic fever (temperature >38.5 °C and neutrophils <0.5)","definition_or_measurement_approach":"Count of episodes meeting definition: temperature >38.5 °C with neutrophils <0.5"}
• {"endpoint_text":"- Admission at the intensive care unit (ICU) or pediatric intensive care unit (PICU)","definition_or_measurement_approach":"Recording of ICU/PICU admissions post infusion"}
• {"endpoint_text":"- Death from any cause","definition_or_measurement_approach":"All-cause mortality"}

Secondary endpoints

• {"endpoint_text":"- Response rates defined as complete response, partial response, stable response or progressive disease","definition_or_measurement_approach":"Response rates categorized as CR, PR, stable disease or PD per protocol response criteria"}
• {"endpoint_text":"- Overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM) and treatment with allogeneic hematopoietic stem cell transplantation (HSCT)","definition_or_measurement_approach":"Time-to-event measures (OS, PFS), incidence of NRM and record of subsequent allogeneic HSCT"}

Denmark

Earliest CTIS Part Ii Submission Date

05-06-2024

Latest Decision Or Authorization Date

29-08-2025

Processing Time Days

450

Number Of Sites

1

Number Of Participants

15

Primary sponsor

Full Name

Rigshospitalet

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Third parties

• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"sponsorDuties code 1","organisation_type":"Hospital/Clinic/Other health care facility"}