This Study in Patients With Chronic Lymphocytic Leukaemia is Done to Determine a Safe and Effective Dose of BI 836826 in Combination With Venetoclax

NCT03343678 | Withdrawn Phase 1

• 2 other identifiers: 1270.132014-004957-16
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main objective of this trial is to determine the maximum tolerated dose (MTD) of BI 836826 in combination with venetoclax on the basis of dose limiting toxicities (DLTs incidence rate during the MTD evaluation period of the combination treatment and to determine the recommended Phase II dose (RP2D) of the combination. Other objectives are to evaluate the pharmacokinetics of BI 836826 in combination with venetoclax and to further determine the safety, as well as to evaluate the efficacy of the combination by means of the Complete Response (CR) rate and Minimal Residual Disease (MRD) negativity rate.

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) based on the number of patients with dose limiting toxicities (DLTs) in the MTD evaluation period

  up to 28 days

• Number of patients with dose limiting toxicities (DLTs) in the Maximum tolerated dose (MTD) evaluation period

  up to 28 days

Secondary Outcomes (4)

• Area under the plasma concentration-time curve at steady-state (AUCtau) of BI 836826 when administered in combination with venetoclax with an observation time of 28 days in Cycle 1 of the combination.

  up to 28 days

• Complete response (CR) defined by investigator's assessment based on response assessment at imaging time points, analysed by complete response rate

  up to 36 months

• Minimal residual disease (MRD) negativity based on blood and analysed by MRD negativity rate

  up to 36 months

• Minimal residual disease (MRD) negativity based on bone marrow and analysed by MRD negativity rate

  up to 36 months

Study Arms (1)

Venetoclax + BI 836826

EXPERIMENTAL

Drug: Venetoclax; Drug: BI 836826

Interventions

Venetoclax DRUG

Venetoclax given alone and then in combination with BI 836826

Venetoclax + BI 836826

BI 836826 DRUG

Venetoclax given in combination with BI 836826

Venetoclax + BI 836826

Eligibility Criteria

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

You may qualify if:

• Diagnosis of Chronic Lymphocytic Leukaemia (CLL) according to International Workshop for Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria documented in medical records
• Indication for treatment of CLL based on investigator's assessment consistent with accepted IWCLL criteria
• Relapsed or refractory CLL after standard therapy in line with the following requirements:
• Presence of TP53 (Tumour Protein) mutation or deletion (17p), AND at least one prior therapy for CLL with a B-cell receptor pathway inhibitor or contra-indication to the prescription of a B-cell receptor pathway inhibitor OR
• Absence of TP53 mutation or deletion (17p) AND at least 2 prior treatment regimens for CLL including:
• at least 4 cycles of chemo-immunotherapy containing a CD20-targeting monoclonal antibody, i.e. at least 4 doses of a monoclonal antibody and at least 4 doses of a cytotoxic AND
• a B-cell receptor pathway inhibitor
• Clinically quantifiable disease burden defined as
• either Absolute Lymphocyte Count (ALC) \>10x10\^9/L, or
• measurable lymphadenopathy (at least one node \> 2 cm on Computed Tomography (CT) scan) or
• quantifiable bone marrow infiltration documented in a bone marrow biopsy during screening if applicable
• Resolution of all clinically relevant acute non-hematologic toxic effects of any prior antitumour therapy to Grade \<=1 with the exception of alopecia or neurotoxicity (Grade 1 or 2 neurotoxicity permitted) prior to the first dose of venetoclax
• Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2
• Patient of full age (according to local legislation, usually \>= 18 years) at screening.
• Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per International Conference on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.

You may not qualify if:

• Known transformation of Chronic Lymphocytic Leukaemia (CLL) to an aggressive B-cell malignancy at the time of screening (e.g. large B-cell lymphoma, Richter's syndrome)
• History of a non-CLL malignancy except for the following:
• adequately treated local basal cell or squamous cell carcinoma of the skin,
• cervical carcinoma in situ,
• superficial bladder cancer,
• asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for \>=1 year prior to enrolment,
• other adequately treated Stage 1 or 2 cancer currently in complete response,
• or any other cancer that has been in complete response for \>=2 years.
• Ongoing systemic immunosuppressive therapy other than corticosteroids
• Previous treatment with a CD37-targeting antibody or antibody drug conjugate
• Absolute neutrophil count \< 1 x 10\^9/L
• Platelet count \< 50 x 10\^9/L
• Aspartate Transaminase (AST) and/or Alanine Transaminase (ALT) \> 3 times the upper limit of normal (ULN) range
• Bilirubin \> 1.5 time ULN range with the exception of known Gilbert's syndrome
• Estimated glomerular filtration rate (GFR) \<30 mL/min/1.73m2 (based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

venetoclax; BI 836826

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

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2017
• First Posted: November 17, 2017
• Study Start: January 17, 2018
• Primary Completion: May 25, 2018
• Study Completion: November 25, 2020
• Last Updated: January 9, 2018

Record last verified: 2018-01