Clinical Study With Ibrutinib and Venetoclax for Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia

NCT04754035 | Unknown Phase 2 DMC

• 1 other identifier: PS-CLL-002
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2a, multicenter, open-label uncontrolled study aimed at determining therapeutic benefits of the addition of ibrutinib to venetoclax in patients with relapsed/refractory CLL based on a MRD-guided approach.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Minimal residual disease

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

  4 years

Secondary Outcomes (8)

• Complete response (CR) rate

  4 years

• Progression-free survival (PFS) rate at 12 months

  1 year

• Progression Free Survival (PFS)

  4 years

• Overall response rate (ORR)

  4 years

• Duration of response (DOR)

  4 years

Study Arms (1)

venetoclax + ibrutinib

EXPERIMENTAL

Drug: Venetoclax; Drug: Imbruvica Oral Product

Interventions

Venetoclax DRUG

venetoclax 20 mg, 50 mg, 100 mg

venetoclax + ibrutinib

Imbruvica Oral Product DRUG

Imbruvica 140 mg

venetoclax + ibrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age
• Documented CLL requiring treatment according to the IWCLL criteria (Hallek M et al, 2008)
• Relapsed/refractory CLL patients who received at least 1 prior therapy
• Adequate bone marrow function without transfusion \< 2 weeks of screening as follows:
• Absolute neutrophil count (ANC) ≥1.0 x 109/L (growth factors administration is allowed)
• Platelets ≥30 x 109/L. If thrombocytopenia due to BM involvement, platelets should be ≥ 20 x 109/L
• Hemoglobin value ≥8.0 g/dl
• The patient has adequate renal and hepatic function per local reference laboratory reference ranges as follows:
• Renal: patient has a creatinine clearance (CrCl) ≥ 30 mL/min
• Hepatic: AST and ALT ≤ 3 × the upper normal limit (ULN) of institution's normal range and bilirubin ≤ 1.5 × ULN. Patients with AIHA and Gilbert's syndrome may have a bilirubin \> 1.5 × ULN, but these conditions must be clearly documented in clinical records.
• Female patients of childbearing potential and non-sterile male patients must practice at least one of method of birth control with partner(s) beginning with initial treatment administration and continuing to 30 days after the last dose of study treatment. Female of child bearing potential must have a negative serum pregnancy test upon study entry
• Male patient must agree to refrain from sperm donation, from initial treatment administration until 90 days after the last dose of treatment
• Ability to provide written informed consent and to understand and comply with the requirements of the study

You may not qualify if:

• Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leukemia)
• Known central nervous system (CNS) involvement
• Inadequate renal function: CrCl \<30 mL/min
• Previous treatment with BTK and/or BCL2 inhibitors (patients previously treated with PI3K inhibitors are eligible)
• Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
• 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
• Treatment, administration or consumption of any of the following within 3 days prior to the first dose of venetoclax (see also Appendix G):
• Strong Cytochrome P450 3A (CYP3A) inhibitors
• Moderate CYP3A inhibitors
• Moderate or strong CYP3A inducers
• PI3K inhibitor (e.g. Idelalisib);
• Grapefruit or grapefruit products
• Seville oranges (including marmalade containing Seville oranges)
• Star fruit
• 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.

Sponsors & Collaborators

• Paolo Ghia: lead

Study Sites (1)

Ospedale San Raffaele

Milan, MI, 20132, Italy

Location

Related Publications (1)

• Scarfo L, Heltai S, Albi E, Scarano E, Schiattone L, Farina L, Moia R, Deodato M, Ferrario A, Motta M, Reda G, Sancetta R, Coscia M, Rivela P, Laurenti L, Varettoni M, Perotta E, Capasso A, Ranghetti P, Colia M, Ghia P. Minimal residual disease-driven treatment intensification with sequential addition of ibrutinib to venetoclax in R/R CLL. Blood. 2022 Dec 1;140(22):2348-2357. doi: 10.1182/blood.2022016901.

  PMID: 35921541 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Paolo Ghia, Prof

  San Raffaele Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Venetoclax will be administered, initially as single agent, orally once daily (QD), starting with 20 mg on Day 1, followed by weekly dose escalation up to 400 mg At Cycle 12 Day 1 Minimal residual disease (MRD) in the peripheral blood will be evaluated in patients with CR or PR by flow cytometry. All MRD negative subjects (defined as those with MRD level in the PB \<10-4 in the PB and in the BM aspirate) will discontinue venetoclax at the end of Cycle 12. All MRD positive subjects (defined as those with MRD level in the PB \>10-4) and patients with stable disease will continue venetoclax and start treatment with ibrutinib at the standard dose for CLL of 420 mg QD. Venetoclax will be administered until unacceptable toxicity or disease progression or for a maximum of 2 years and ibrutinib will be continued until unacceptable toxicity, confirmed MRD negativity, or disease progression.

Study Record Dates

• First Submitted: July 7, 2017
• First Posted: February 15, 2021
• Study Start: November 8, 2017
• Primary Completion: July 31, 2018
• Study Completion: September 1, 2025
• Last Updated: October 3, 2023

Record last verified: 2023-10

Locations

IT (1)