Phase IV VR in relapsed CLL – Polish experience

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Uniwersytet Medyczny W Lublinie

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-06-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Medical Research Agency, Chmielna 69 Street, 00-801 Warszawa

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

Evaluation of the efficacy of venetoclax + rituximab (VR) treatment in clinical practice, based on the percentage of patients achieving MRD negativity (uMRD, MRD<10-4)

Secondary objectives 5

1. Assessment of treatment effectiveness based on ORR, PR, CR and CRi, uMRD indicators for patients treated with the VR regimen in the Ministry of Health drug program, taking into account pharmacoeconomic and systemic parameters including the number of hospitalization days and visits during 24 months
2. Assessment of ORR, PR, CR and CRi, uMRD in patients with negative prognostic factors: TP53 deletion/mutation, unmutated IGHV genes and high CD38 expression
3. Evaluation of potential biomarkers, including cytogenetic abnormalities detected by FISH, IGVH gene mutational status, and TP53 mutations assessed by Sanger or next-generation sequencing (NGS), that have prognostic or predictive significance for VR treatment response and resistance
4. Assessment of the quality of life (QoL) of the subjects during therapy – changes from baseline in QoL measurements assessed using the QLQ-C30 questionnaire (EORTC QLQ-C30)
5. Analysis of the number of hospitalization days in each of the studied regimens, taking into account the period associated with venetoclax titration

Conditions and MedDRA coding

Adult with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL)

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 25

1. Age > 18 years
2. Obtaining the patient's informed voluntary consent to participate in the study
3. Ability and willingness to comply with the requirements of the study protocol
4. The patient must have a diagnosis of CLL (CLL or SLL) that meets the criteria published in 2018 iwCLL
5. Meeting the criteria for qualifying for therapy under the B.79 drug program
6. Performance status 0-2 according to the ECOG scale
7. Presence of indications for treatment according to the International Workshop on Chronic Lymphocytic Leukemia updating (the National Cancer Institute-Working Group (iwCLL)
8. There are no contraindications to the use of the drug in accordance with the current Summary of Product Characteristics
9. No hypersensitivity to any drug or mouse proteins or any of the excipients of the drug
10. Exclusion of pregnancy and breastfeeding
11. Patient consent to contraception in accordance with the relevant, current Summary of Product Characteristics
12. Absence of active, severe infections
13. Absence of significant comorbidities or clinical conditions constituting a contraindication to therapy, as determined by the attending physician based on the relevant, current Summary of Product Characteristics
14. Adequate organ function, determined on the basis of laboratory blood test results, enabling, in the opinion of the attending physician, safe commencement of therapy
15. Prior treatment for CLL or SLL, including chemotherapy, BTK inhibitor therapy, venetoclax, small molecule signaling inhibitor, or monoclonal antibody therapy with response to previous venetoclax treatment > 36 months from last dose
16. Adequate hematologic function independent of growth factors or transfusion support, according to the local laboratory reference range at screening (unless due to underlying disease, as evidenced by extensive bone marrow involvement or hypersplenism secondary to splenic lymphoma according to the investigator), defined as follows: • Hemoglobin ≥ 9 g/dL • Absolute neutrophil count ≥ 1.0 × 109/L • Platelet count ≥ 75 × 109/L
17. Adequate renal function, according to the local laboratory reference range at screening, as indicated by: Calculated creatinine clearance ≥ 30 mL/min/1.73 m² using 24-hour creatinine clearance or the modified Cockcroft-Gault equation (eCCR; using ideal body weight [IBM] instead of weight)
18. Normal liver function, according to the local laboratory reference range for screening, as indicated by: • AST and ALT ≤ 2.5 × ULN • Total bilirubin ≤ 1.5 × ULN (or ≤ 3 × ULN in patients with documented Gilbert's syndrome)
19. Absence of active hemolytic anemia requiring immunosuppressive or other pharmacological treatment. Patients with a positive Coombs test but no evidence of hemolysis are NOT excluded from participation in the study
20. No current use of corticosteroids. EXCEPTION: Low-dose steroids (<10 mg prednisone or equivalent dose of another steroid) are permitted for the treatment of non-hematological conditions (e.g., chronic adrenal insufficiency)
21. No prior autoimmune complications (e.g., autoimmune hemolytic anemia or immune thrombocytopenia) that have developed since the initial diagnosis of CLL and required treatment with high-dose corticosteroids (e.g., equivalent to >20 mg prednisone daily), monoclonal antibody-based therapy, or chemotherapy. Previous use of corticosteroids for reasons other than the treatment of autoimmune complications of CLL is permitted
22. No major surgery within 4 weeks (28 days) of the first dose of study drug or minor surgery within 3 days of the first dose of study drug
23. No radiotherapy ≤ 4 weeks before starting study treatment
24. The patient must be able to take a xanthine oxidase inhibitor or rasburicase for tumor lysis syndrome (TLS) prophylaxis
25. Negative pregnancy test result (serum βHCG concentration) for women of reproductive age (including premenopausal women who have had tubal ligation) and for all women who do not meet the definition of postmenopausal (≥ 24 months of amenorrhea) and who have not undergone surgical sterilization through hysterectomy and/or bilateral oophorectomy. For all other women, documentation confirming that the patient is not of reproductive age should be provided in the medical interview. ● Patients who are not surgically sterile or postmenopausal must agree to the simultaneous use of two reliable forms of contraception or to complete abstinence from heterosexual intercourse during the study. ● Men must agree to use a latex condom during sexual contact with women of reproductive age during the study and for at least 28 days after discontinuing the study, even if they have had a successful vasectomy

Exclusion criteria 8

1. Disease progression during treatment, including transformation to a more aggressive lymphoma
2. Occurrence of hypersensitivity symptoms to any of the drugs used or to mouse proteins or to any of the excipients of the drug, preventing continuation of treatment
3. Occurrence of unacceptable or life-threatening toxicity despite appropriate management
4. Occurrence of progressive multifocal leukoencephalopathy or severe skin reactions (toxic epidermal necrolysis, Stevens-Johnson syndrome) – in case of venetoclax therapy in combination with anti-CD20 antibody
5. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia – in the case of therapy with venetoclax as monotherapy or in combination with an anti-CD20 monoclonal antibody or ibrutinib
6. Pregnancy or breastfeeding
7. The occurrence of diseases or conditions which, in the opinion of the attending physician, make further treatment impossible
8. Lack of cooperation or failure to follow medical recommendations, including those regarding periodic check-ups to assess the effectiveness and safety of treatment, on the part of the beneficiary or his/her legal guardian

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients treated with venetoclax + rituximab (VR) achieving uMRD status, i.e. MRD values ​​<10-4 determined by flow cytometry

Secondary endpoints 5

1. Percentage of patients achieving ORR, PR, CR and Cri, uMRD, treated according to the VR regimen in the Ministry of Health drug program, taking into account pharmacoeconomic and systemic parameters including the number of days of hospitalization and visits during 24 months
2. Percentage of patients achieving ORR, PR, CR and Cri, uMRD with negative prognostic factors: TP53 deletion/mutation, unmutated IGHV gene and high CD38 expression
3. Occurrence and correlation with treatment outcomes of potential biomarkers, including cytogenetic abnormalities detected by FISH, mutational status of the IGVH gene and TP53 mutations assessed by Sanger or next-generation sequencing (NGS), in patients treated according to the VR regimen
4. Results of the QLQ-C30 (EORTC QLQ-C30) questionnaires assessing quality of life (QoL), completed by patients before and during treatment
5. Number of days of hospitalization in each of the studied regimens, taking into account the period related to venetoclax titration

Investigational products

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

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Uniwersytet Medyczny W Lublinie

Sponsor organisation

Uniwersytet Medyczny W Lublinie

Address

Ul. Aleje Raclawickie 1

City

Lublin

Postcode

20-059

Country

Poland

Scientific contact point

Organisation

Uniwersytet Medyczny W Lublinie

Contact name

Krzysztof Giannopoulos

Public contact point

Organisation

Uniwersytet Medyczny W Lublinie

Contact name

Krzysztof Giannopoulos

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Results and documents

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

Documents 16 files

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

Application history

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