Clinical trial with Ibrutinib and Venetoclax for patients with Relapsed/Refractory Chronic Lymphocytic Leukemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale San Raffaele S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

10 Mar 2017 → ongoing

Decision date (initial)

2024-08-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514686-19-00

EudraCT number

2016-004707-32

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To evaluate the efficacy of the addition of ibrutinib to venetoclax in terms of minimal residual disease (MRD) negativity in patients with relapsed/refractory CLL

Conditions and MedDRA coding

Relapsed or Refractory Chronic Lymphocytic Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Documented CLL requiring treatment according to the IWCLL criteria (Hallek et al. 2008)
2. Relapsed/refractory CLL patients who received at least 1 prior therapy
3. Adequate bone marrow function without transfusion < 2 weeks of screening as follows: a. Absolute neutrophil count (ANC) =1.0 x 109/L (growth factors administration is allowed) b. Platelets =30 x 109/L. If thrombocytopenia due to BM involvement, platelets should be = 20 x 109/L c. Hemoglobin value =8.0 g/dl

Exclusion criteria 9

1. Transformation of CLL to aggressive NHL (Richter’s transformation or pro-lymphocytic leukemia)
2. Known central nervous system (CNS) involvement
3. Inadequate renal function: CrCl <30 mL/min
4. Previous treatment with BTK and/or BCL2 inhibitors (patients previously treated with PI3K inhibitors are eligible)
5. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
6. Requires the use of warfarin, marcumar, or phenprocoumon (potential drug-drug interaction increasing exposure of warfarin or phenprocoumon): low molecular weight drugs e.g. heparin are acceptable
7. Treatment, administration or consumption of any of the following within 3 days prior to the first dose of venetoclax (see also Appendix G). a. Strong Cytochrome P450 3A (CYP3A) inhibitors b. Moderate CYP3A inhibitors c. Moderate or strong CYP3A inducers d. PI3K inhibitors (e.g. Idelalisib); e. Grapefruit or grapefruit products f. Seville oranges (including marmalade containing Seville oranges) g. Star fruit
8. Known history of human immunodeficiency virus (HIV) or active with hepatitis B virus (HBV) or hepatitis C virus (HCV). Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
9. History of other malignancies, except: a. Malignancy treated with curative intent and with no known active disease present for =3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician. b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. c. Adequately treated carcinoma in situ without current evidence of disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Minimal residual disease (MRD) negativity rate evaluated by multi-colour flow cytometry analysis (limit of detection 10-4) within the treatment period

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale San Raffaele S.r.l.

Sponsor organisation

Ospedale San Raffaele S.r.l.

Address

Via Olgettina 60

City

Milan

Postcode

20132

Country

Italy

Scientific contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Paolo Ghia

Public contact point

Organisation

Ospedale San Raffaele S.r.l.

Contact name

Paolo Ghia

Locations

1 EU/EEA country · 17 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

Documents 4 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