relapsed / refractory Chronic Lymphocytic Leukemia relapsed / refractory Small Lymphocytic Lymphoma
Conditions
Interventions
Product Name: BCN-CP01
Product Code: BCN-CP01
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: anti-CD19 CAR T cells
Current Sponsor code: BCN-CP01
Other descriptive name: CD19 CAR T
Sponsors
CellPoint B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form 2. Age = 18 years 3. Histologically confirmed diagnosis of CD19+ CLL or SLL with an indication for therapy according to iwCLL criteria, Richter’s transformation is allowed 4. Documented relapsed or refractory disease after at least 2 prior lines of therapy: • Subjects must have been exposed to Bruton tyrosine kinase (BTK)-inhibitors (e.g. ibrutinib, acalabrutinib) • Richter’s patients who failed a BTK-inhibitor are eligible regardless of number of prior lines of therapy received 5. Measurable disease according to iwCLL 6. ECOG performance status of 0 or 1 7. Adequate bone marrow function defined as: • Absolute neutrophil count (ANC) = 500/µL or = 0.5 × 109/L (without G-CSF support within 7 days of the laboratory test or pegylated G-CSF support within 14 days of the laboratory test) • Platelet count = 50.000/µL or = 50 x 109/L (without prior platelet transfusion within 7 days before the laboratory test) • Absolute lymphocyte count = 300/µL or = 0.3 × 109/L; • CD3+ count = 150/µL or = 0.15 × 109/L 8. Adequate renal, hepatic and pulmonary function defined as: • Serum albumin = 3.4 g/dL • Creatinine clearance (Cockcroft Gault) = 30 mL/min • Aspartate aminotransferase (AST) = 3 × upper limit of normal (ULN) • Alanine aminotransferase (ALT) = 3 × ULN • Total bilirubin = 2 x ULN, except in subjects with Gilbert’s syndrome • No clinically significant pleural effusion • Baseline oxygen saturation > 92% on room air 9. Women of childbearing potential must have a negative serum pregnancy test at screening and prior to the first dose of cyclophosphamide and fludarabine 10. Women of childbearing potential and all male subjects must agree to use highly effective methods of contraception (failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Prior treatment: • Any anti-CD19 targeted therapy • Salvage systemic therapy within 2 weeks or 5 half-lives (whichever is shorter) prior to leukapheresis • Allogeneic stem cell transplant within 6 months before leukapheresis. Subjects who received an allogeneic transplant must have stopped all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease. Subjects with active significant (overall Grade = II, Seattle criteria) active graft-versus-host disease (GVHD) or moderate/ severe chronic GVHD (NIH consensus criteria) requiring systemic steroids are excluded. • Corticosteroid therapy at a pharmacologic dose (> 10 mg/day of prednisone or equivalent doses of other corticosteroids) and other immunosuppressive drugs are not allowed for 7 days prior to leukapheresis and > 72 hours prior to BCN-CP01 infusion (if restarted) 2. History of malignancy other than lymphoma, except: a. non-melanoma skin cancer b. Carcinoma in situ (e.g. skin, cervix, bladder, breast) and disease free for at least 3 years prior to screening c. Superficial bladder cancer d. Asymptomatic low-grade or curatively treated localized prostate cancer for which watch-and-wait approach is standard of care e. Any other cancer that has been in remission for =3 years prior to enrollment 3. History of BTK-associated side effects (e.g. symptomatic atrial fibrillation) or co-morbidities (e.g. oral anticoagulation use , severe hemophilia, or von Willebrand’s disease, etc.) that would prevent the patient from taking ibrutinib during the screening phase 4. Contraindication for Fludarabine or Cyclophosphamide 5. Known allergy or hypersensitivity to tocilizumab 6. Toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less 7. Active CNS involvement (with neurological changes) by disease under study, except if the CNS involvement has been effectively treated (i.e. patient is asymptomatic) and local treatment was > 4 weeks before screening 8. Clinically significant cardiac disease within 12 months of screening such as: • Impaired cardiac function (LVEF < 45%) as assessed by echocardiogram performed = 4 weeks prior to screening • Evidence of pericardial effusion as determined by echocardiogram • New York Heart Association Class III or IV congestive heart failure • Clinically significant arrhythmias 9. Primary immunodeficiency 10. Stroke or seizure within 6 months of screening 11. History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within 2 years prior to screening 12. Infection with HIV, hepatitis B or hepatitis C virus. A history of hepatitis B or C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing. 13. Uncontrolled infection or infection requiring antimicrobials for management, at screening 14. Vaccinated with live attenuated vaccine = 4 weeks prior to leukapheresis 15. Pregnant or nursing women, or planning to become pregnant within 6 months after BCN-CP01 infusion 16. No major surgery =2 weeks prior to leukapheresis 17. In the investigator’s judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the phase I part of the study is to evaluate the safety and preliminary efficacy of BCN-CP01 to determine the RP2D. The primary objective of the phase II part of the study is to evaluate the efficacy of BCMCP03, as measured by the objective response rate (ORR).;Secondary Objective: Secondary objectives include further assessment of the safety of BCN-CP01, additional efficacy endpoints (CRR, MRD-, DOR, PFS, OS), pharmacokinetics and pharmacodynamics of BCN-CP01, as well as the feasibility of point of care manufacture of BCN-CP01.;Primary end point(s): Phase I: - Incidence of (serious) adverse events, including dose-limiting toxicities (DLT) Phase II: - Best objective response rate per iwCLL response criteria (Lugano classification for Richter’s transformation);Timepoint(s) of evaluation of this end point: Safety (including DLTs) and efficacy data are reviewed on a continuous basis throughout the study. After completion of Phase I, safety and efficacy data will be evaluated to determine the RP2D. The primary analyses will be conducted when all subjects have completed at least one response assessment. Final study report will be conducted when all subjects have completed the 2 years disease response assessment, are lost to follow-up, withdraw from the study, or die, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Type, frequency and severity of (S)AEs (including AEs of special interest), and clinically significant laboratory abnormalities - Objective response rate (ORR) per iwCLL response criteria or Lugano classification for Richter’s transformation (Phase I) - Duration of response (DOR) - Minimal residual disease (MRD) negative response rate - Overall survival (OS) - Progression free survival (PFS) - Duration of response (DOR) - Levels of BCN-CP01 cells in blood, bone marrow, CSF, and other tissues over time - Levels of chemokines and cytokines in serum over time - Number of successfully manufactured BCN-CP01 products within the predefined release specifications - Number of patients infused with planned target dose - Immunogenicity: cellular and humoral responses to the CAR transgene;Timepoint(s) of evaluation of this end point: The primary analyses will be conducted when all subjects have completed at least one response assessment. Final study report will be conducted when all subjects have completed the study (after LVLS). | — |
Countries
Spain
Contacts
Public ContactClinical Operations
CellPoint B.V.
Outcome results
None listed