A study evaluating the safety and efficacy of anti-CD19 CAR T in subjects with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Galapagos

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Feb 2022 → 25 Aug 2025

Decision date (initial)

2023-07-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2022-501686-47-00

EudraCT number

2021-003815-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Pharmacokinetic, Others

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 BCN-CP01, as measured by the objective response rate (ORR).

Conditions and MedDRA coding

relapsed/refractory chronic lymphocytic leukemia relapsed/refractory small lymphocytic leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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: 1) Subjects must have been exposed (or be intolerant/ineligible or did not consent) to Bruton tyrosine kinase (BTK)-inhibitors (e.g. ibrutinib, acalabrutinib), BCL2-inhibitors (e.g. venetoclax) and/or PI3K inhibitors (e.g. idelalisib, duvelisib); 2) 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: 1) 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); 2) Platelet count ≥ 50,000/μL or ≥ 50 x 109/L (without prior platelet transfusion within 7 days before the laboratory test); 3) Absolute lymphocyte count ≥ 300/μL or ≥ 0.3 × 109/L; 3) CD3+ count ≥ 150/μL or ≥ 0.15 × 109/L
8. Adequate renal, hepatic and pulmonary function defined as: 1) Serum albumin ≥ 3.4 g/dL; 2) Creatinine clearance (Cockcroft Gault) ≥ 30 mL/min; 3) Aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN); 4) Alanine aminotransferase (ALT) ≤ 3 × ULN; 5) Total bilirubin ≤ 2 x ULN, except in subjects with Gilbert's syndrome; 6) No clinically significant pleural effusion; 7) 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 < 1% per year when used consistently and correctly) and agree to remain on a highly effective method of contraception from the time of signing the informed consent form until at least 6 months after BCN-CP01 infusion. Subjects must agree to not donate eggs or sperm during this period.

Exclusion criteria 1

1. 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, 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 12 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase I: Incidence of (serious) adverse events, including dose-limiting toxicities (DLT)
2. Phase II: Best objective response rate per iwCLL response criteria (Lugano classification for Richter's transformation)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Galapagos

Sponsor organisation

Galapagos

Address

Generaal De Wittelaan L11 A3

City

Mechelen

Postcode

2800

Country

Belgium

Scientific contact point

Organisation

Galapagos

Contact name

Marte Liefaard

Public contact point

Organisation

Galapagos

Contact name

Marte Liefaard

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications