Acute Lymphoblastic Leukemia and B-cell Non Hodgkin Lymphoma MedDRA version: 21.1 Level: LLT Classification code 10066109 Term: Precursor B-lymphoblastic leukemia acute System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10012855 Term: Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl
Conditions
Interventions
Product Name: DK-CLIC -1901
Pharmaceutical Form: Injection/infusion
INN or Proposed INN: DK-CLIC-1901
Other descriptive name: CD19CAT-41BBZCAR T-CELLS (CD19CAR T-CELLS)
Concentration unit: Other
Conce
Sponsors
Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Relapsed/refractory hematologic disease (in peripheral blood, bone marrow or lymph node biopsy by flow cytometry) defined as one of the following: a. CD19 expressing B-cell acute lymphoblastic leukemia (B-ALL) with one of the following: • Second or greater bone marrow (BM) relapse. • Any relapse after allogeneic haematopoietic stem cell transplantation (HSCT). • Primary 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. • Philadelphia chromosome-positive ALL intolerant of or with 2 failed lines of tyrosine kinase inhibitor (TKI) therapy or if TKI therapy is contraindicated. • Ineligible 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. Histologically 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, primary mediastinal large B-cell lymphoma, mantle cell lymphoma, Richter-transformed chronic lymphocytic lymphoma (CLL) or transformed follicular lymphoma with one of the following: • Second or greater relapse. • Relapse after autologous or allogeneic haematopoietic stem cell transplantation (HSCT). • Primary refractory, defined as not achieving partiel remission (PR) at time of interim-scanning or as defined in frontline protocol. 2. Age of 1-70 years 3. Life expectancy = 12 weeks after enrollment 4. Adequate organ function defined as: a. Lansky (16 years) score > 50% b. FEV1 or DLCOc = 40 % of expected and oxygen saturation > 90% without oxygen supply c. LVEF > 45% and no symptoms of ischemic heart disease d. Bilirubin 40mL/min (adults) or >30% of normal limit for age (children) 5. Signed statement of consent after receiving oral and written study information 6. Agreement 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. Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: o 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) o Patients with concomitant genetic syndrome, such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known familial bone marrow failure syndrome o Prior treatment with any gene therapy product o Treatment with any investigational agent within 30 days prior to enrollment o Treatment with allogeneic haematopoietic stem cell transplantation within 6 months or donor lymphocyte infusion within 6 weeks from CAR-T infusion o Acute or chronic graft-versus-host disease with the need for systemic corticosteroid treatment within 4 weeks prior to enrollment o Acute or chronic infections with HIV o Active infection with, hepatitis B or hepatitis C o Active severe bacterial, viral or fungal infection o 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). o Pre-existing significant central neurological disorder defined as CTCAE grade 3-4 (other than CNS involvement of underlying hematological malignancy) o History of anaphylaxis to gentamicin or its derivates o Pregnant or breastfeeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To test safety and feasibility of treatment with CLIC-1901 CAR T-cell in relapsed or refractory CD19-expressing hematological malignancies.;Secondary Objective: To test efficacy of treatment with CLIC-1901 CAR T-cells and analyse factors contributing to to non-efficacy;Primary end point(s): oCRS: registration according to international grading system[31]. Endpoints include proportion of patients experiencing CRS of all grades and CRS grade 3-4. oNeurotoxicity: registration according to international grading system[31]. Endpoints include proportion of patients experiencing neurotoxicity of all grades and neurotoxicity grade 3-4. oTreatment with tocilizumab and/or glucocorticoids. oProlonged cytopenia, including 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. oEpisodes of neutropenic fever (temperature >38.5 °C and neutrophils <0.5) . oAdmission at the intensive care unit (ICU) or pediatric intensive care unit (PICU) oDeath from any cause ;Timepoint(s) of evaluation of this end point: 28 days, 90 days, 180 days, 365 days and 730 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): o Response rates defined as complete response, partial response, stable response or progressive disease o Overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM) and treatment with allogeneic hematopoietic stem cell transplantation (HSCT) ;Timepoint(s) of evaluation of this end point: at time points 28 days, 90 days, 180 days, 365 days and 730 days. | — |
Countries
Denmark
Contacts
Public ContactKatrine Kielsen
Rigshospitalet
Outcome results
None listed