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

Phase 1

• Conditions: Relapsed or Refractory Chronic Lymphocytic Leukemia; MedDRA version: 21.0Level: LLTClassification code 10008957Term: Chronic lymphatic leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2016-004707-32-IT
• Lead Sponsor: OSPEDALE SAN RAFFAELE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-01
• Last Update Posted: 2 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion Criteria

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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;Secondary Objective: 1) To evaluate the safety of the addition of ibrutinib to venetoclax in patients with relapsed/refractory CLL<br>2) To evaluate the efficacy of the addition of ibrutinib to venetoclax in terms of overall response rate, partial and complete response rate, progression-free survival, duration of response and overall survival in patients with relapsed/refractory CLL<br>;Primary end point(s): ¿Minimal residual disease (MRD) negativity rate evaluated by multi-colour flow cytometry analysis (limit of detection 10-4) within the treatment period;Timepoint(s) of evaluation of this end point: during treatment period

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) Complete response (CR) rate <br>2) Progression-free survival (PFS) rate at 12 months<br>3) PFS<br>4) Overall response rate (ORR)<br>5) Duration of response (DOR)<br>6) Overall Survival (OS);<br>7) Safety [type, frequency, and severity of adverse events (AEs) and relationship of AEs], premature withdrawals.<br>;Timepoint(s) of evaluation of this end point: during treatment period and follow up