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Leukemia, Lymphocytic, Chronic, B-CellPhase 1NCT03343678

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

A Phase 1 study testing Venetoclax and BI 836826 in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Boehringer Ingelheim.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Lymphocytic, Chronic, B-Cell
What is being tested?
Venetoclax and BI 836826
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
17 Jan 2018to 25 Nov 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • Signed and dated written informed consent in accordance with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial

Who cannot join

  • 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,
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  • 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)
  • Human Immunodeficiency virus (HIV) infection
  • Active hepatitis B infection (defined as presence of Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA). (Note: Laboratory tests performed as routine procedure prior to signing ICF but within 2 weeks prior to Cycle 1 Day 1 may be used).
  • Cytomegalovirus (CMV) viraemia (Note: Laboratory tests performed as routine procedure prior to signing Informed Consent Form (ICF) but within 2 weeks prior to Cycle 1 Day 1 may be used).
  • Active bacterial, viral, or fungal infection requiring systemic treatment.
  • Other concomitant clinically significant illness, medical condition, surgical history, physical finding, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring therapy (with the exception of extrasystoles or minor conduction abnormalities), Electrocardiogram (ECG) finding, or laboratory abnormality that in the investigator's opinion could potentially adversely affect the safety of the patient or impair the assessment of trial results
  • Known or suspected hypersensitivity to the trial medications or excipients
  • Known allergy to xanthine oxidase inhibitors and/or rasburicase in patients at risk of Tumour Lysis Syndrome (TLS)
  • Prior treatment with a BCL2i (B-Cell Lymphoma-2 protein) unless the patient has started venetoclax treatment and is still in the ramp-up phase
  • Use of a strong CYP3A inhibitor (e.g., ketoconazole, ritonavir, clarithromycin, itraconazole, voriconazole, posaconazole) or of a moderate CYP3A inhibitor (e.g., erythromycin, ciprofloxacin, diltiazem, fluconazole, verapamil), use of a strong CYP3A inducer (e.g., carbamazepine, phenytoin, rifampicin) or a moderate CYP3A inducer (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) within five times the half-life of the drug before the initiation of the venetoclax ramp-up period
  • Use of a Permeability GlycoProtein (P-gp) inhibitor (e.g., rifampicin) or a breast cancer resistance protein (BCRP) inhibitor within five times the half-life of the drug before the initiation of the venetoclax ramp-up period
  • Women who are pregnant, breastfeeding, or who plan to become pregnant while in the trial
  • Patients unable to comply with protocol
  • Persons with any kind of dependency on the investigator or employed by the sponsor or investigator
  • Patients who are under judicial protection and patients who are legally institutionalized
  • Concomitant participation to a non-CLL investigational device or drug trial or within 30 days after end of participation
  • Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial

About this study

Official title: An Open-label, Multi-centre, Phase Ib Trial to Determine the Dose of Intravenous BI 836826 in Combination With Oral Venetoclax in Chronic Lymphocytic Leukaemia Patients Who Are Eligible for Treatment With Venetoclax

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.

Being tested
Venetoclax, BI 836826
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VenetoclaxDrug

    Venetoclax given alone and then in combination with BI 836826

  • BI 836826Drug

    Venetoclax given in combination with BI 836826

Study groups in NCT03343678
Study groupRoleWhat they receive
Venetoclax + BI 836826ExperimentalNot described
Receives: Drug: Venetoclax; Drug: BI 836826

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: up to 28 days

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

    Measured: up to 28 days

Secondary outcomes (4)

  1. 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.

    Measured: up to 28 days

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

    Measured: up to 36 months

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

    Measured: up to 36 months

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

    Measured: up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2017
  2. Study start17 Jan 2018 (estimated)
  3. Primary completion25 May 2018 (estimated)
  4. Study completion25 Nov 2020 (estimated)

Why it stopped: Company strategic decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03343678
Sponsor's protocol ID
1270.13
Other IDs
2014-004957-16, 2014
Status last verified
Jan 2018
First submitted
13 Nov 2017
Last updated
9 Jan 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax and BI 836826 in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Boehringer Ingelheim.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 9 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) based on the number of patients with dose limiting toxicities (DLTs) in the MTD evaluation period (time frame: up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03343678.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2018.

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