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Leukemia, Lymphocytic, Chronic, B-CellPhase 1NCT02759016

Intravenous BI 836826 in Combination With Ibrutinib in Relapsed/Refractory CLL Patients Who Have Been Pre-treated With at Least One Prior Line of Systemic Therapy, and Who Are Eligible for Treatment With Ibrutinib

A Phase 1 study testing BI 836826 and Ibrutinib in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Boehringer Ingelheim at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Intravenous BI 836826 in combination with ibrutinib in relapsed/refractory Chronic Lymphocytic Leukemia (CLL) patients who have been pre-treated with at least one prior line of systemic therapy, and who are eligible for treatment with ibrutinib. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Leukemia, Lymphocytic, Chronic, B-Cell
What is being tested?
BI 836826 and Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
3 sitesUnited States
Study dates
23 Jun 2016to 9 Jul 2019
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of Chronic Lymphocytic Leukemia (CLL) established according to International Workshop Chronic Lymphocytic Leukemia (IWCLL) criteria.
  • Relapsed or refractory CLL pre-treated with at least one prior line of systemic therapy for CLL.
  • Indication for treatment consistent with IWCLL criteria, i.e. at least one of the following criteria should be met
  • Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia.
  • Massive or progressive or symptomatic splenomegaly.
  • Massive nodes or progressive or symptomatic lymphadenopathy.
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  • Progressive lymphocytosis in the absence of infection, with an increase in blood Absolute Lymphocyte Count (ALC) >=50% over a 2-month period, or a lymphocyte doubling time (LDT) of <6 months (as long as initial ALC was >=30000/µl).
  • Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy.
  • Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs:
  • unintentional weight loss of 10% or more within the previous 6 months
  • significant fatigue
  • fevers higher than 100.5°F or 38.0°C for >=2 weeks without other evidence of infection
  • night sweats for > 1 month without evidence of infection
  • Clinically quantifiable disease burden defined as at least one of the following:
  • either ALC >10 000/µL, or
  • measurable lymphadenopathy
  • quantifiable bone marrow infiltration documented in a bone marrow biopsy during screening
  • Resolution of all clinically relevant acute non-hematologic toxic effects of any prior antitumor therapy resolved to Grade <=1
  • Baseline laboratory data as defined as:
  • Hemoglobin (Hb): >=8g/dL Absolute Neutrophil Count (ANC): >=1000/µL Platelet (PLT): >=25000/µL Glomerular Filtration Rate (GFR) or Creatinine Clearance: >=30ml/min Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT): <3 x Upper Limit of Normal (ULN) Bilirubin - total: <1.5 x ULN Activated Partial Thromboplastin Time (aPTT), Prothrombin Time (PT) or International Normalized Ratio (INR): <=1.5 x ULN PT <=1.5 x ULN, INR <=1.5
  • Male or female patients. Women of childbearing potential must agree to use highly effective methods of birth control during the trial and for at least 1 year after the last dose of BI 836826 and 1 month after the last dose of ibrutinib.
  • Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.
  • Age 18 years and older
  • Eligible and able to secure sourcing for ibrutinib
  • Written Informed Consent
  • Further Inclusion criteria apply

Who cannot join

  • Known transformation of Chronic Lymphocytic Leukemia (CLL) to an aggressive B-cell malignancy at the time of screening
  • Prior allogeneic stem cell transplant within one year or active graft vs. host disease.
  • History of a non-CLL malignancy except for adequately treated in situ, stage 1 or 2 carcinoma in Complete Response (CR), or any other cancer that has been in CR for >=2 years after end of cancer treatment.
  • Active, uncontrolled autoimmune cytopenia. Patients with autoimmune cytopenia which is controlled with corticosteroids at doses of <=20 mg prednisolone or equivalent may be enrolled.
  • Previous CLL treatment with a CD37-targeting antibody or a CD37-antibody drug conjugate.
  • Previous treatment with ibrutinib
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  • Previous treatment with another Bruton's Tyrosine Kinase (BTK) -inhibitor.
  • Ongoing systemic immunosuppressive therapy other than corticosteroids.
  • Active bacterial, viral, or fungal infection requiring systemic treatment at the time of study entry.
  • Human Immunodeficiency Virus (HIV) infection
  • Active hepatitis B or C as evidenced by detection of virus specific Deoxyribonucleic Acid (DNA) or Ribonucleic Acid (RNA).
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment
  • Chronic persistent atrial flutter or atrial fibrillation. Patients with intermittent atrial fibrillation may be enrolled if without episode for >= 6 months and without indication for anti-coagulation
  • Requirement for chronic anticoagulation with warfarin or with direct oral anticoagulants at the time of screening.
  • Chronic treatment (i.e. >7 days) with a strong Cytochrome P450 (CYP3A) inhibitor which cannot be terminated prior to the first dose of ibrutinib.
  • Unstable angina pectoris, uncontrolled hypertension, uncontrolled asthma or other pulmonary disease
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial
  • Further Exclusion criteria apply

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • City of Hope

    Duarte, California, 91010

  • Oregon Health and Sciences University

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: A Phase Ib, Open Label, Single Arm, Multi-center, Dose Escalation Trial of Intravenous BI 836826 in Combination With Ibrutinib in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia

Intravenous BI 836826 in combination with ibrutinib in relapsed/refractory Chronic Lymphocytic Leukemia (CLL) patients who have been pre-treated with at least one prior line of systemic therapy, and who are eligible for treatment with ibrutinib. Objectives of the trial are to determine the recommended Phase 2 dose of BI 836826, and to document the safety and tolerability of BI 836826 when given in combination with ibrutinib

Being tested
BI 836826, Ibrutinib
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.

Study groups in NCT02759016
Study groupRoleWhat they receive
BI 836826ExperimentalBI 836826 administered in combination with Standard of Care Ibrutinib
Receives: Drug: BI 836826; Drug: Ibrutinib

What is being measured

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

  1. Recommended Phase 2 Dose of BI 836826 in Combination With Ibrutinib

    The Recommended Phase 2 Dose (RP2D ) of BI 836826 in combination with ibrutinib would be either the Maximum Tolerated Dose (MTD) or a lower dose and would be determined by the safety review committee based on safety and efficacy considerations.

    Measured: First treatment cycle, 4 weeks from first administration of BI 836826.

  2. Number of Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle

    Number of participants with Dose Limiting Toxicities (DLTs) during the first treatment cycle. DLT was defined as any non-hematologic adverse event (AE) of Grade ≥ 3 related to BI 836826 and/or ibrutinib except infusion-related reaction (any Grade), Grade 3 Aspartate Aminotransferase (AST)- and/or Alanine Aminotransferase (ALT) elevation without concomitant bilirubin, elevation or any other asymptomatic Grade 3 laboratory abnormality with spontaneous recovery within 1 week. The following hematologic AEs related to BI 836826 and/or ibrutinib were considered DLT: Grade 4 neutropenia with concomitant infection, Grade 4 febrile neutropenia, and Grade 3 febrile neutropenia not resolving within 72 hours with appropriate treatment (antibiotics, antivirals, antifungals, growth factor support), Grade 4 thrombocytopenia with clinically significant bleeding, Grade 4 anemia, any Grade 5 hematologic AE.

    Measured: First treatment cycle, 4 weeks from first administration of BI 836826.

Secondary outcomes (1)

  1. Maximum Tolerated Dose of BI 836826 in Combination With Ibrutinib

    To determine the Maximum Tolerated Dose (MTD) of BI 836826 in combination with ibrutinib, participants were entered sequentially into dose cohorts starting at 100 mg of BI 836826 and escalating to the MTD in combination with ibrutinib (fixed dose of 420 mg daily). Stepwise dose escalation of BI 836826 was guided by a Bayesian Logistic Regression Model (BLRM) with overdose control. The BLRM estimates the MTD by updating estimates of the probability of observing a Dose Limiting Toxicity (DLT) in the first treatment cycle (4 weeks) for each dose level as participant information becomes available. The MTD would be considered reached if the following criteria were fulfilled. The posterior probability of the true DLT rate in the target interval [0.16 - 0.33) of the MTD is above 0.50 or at least 15 participants have been treated in the study, of which at least 6 at the MTD.

    Measured: First treatment cycle, 4 weeks from first administration of BI 836826.

Timeline

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

  1. First posted3 May 2016 (estimated)
  2. Study start23 Jun 2016
  3. Primary completion3 Jun 2019
  4. Study completion9 Jul 2019

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
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02759016
Sponsor's protocol ID
1270.15
Status last verified
Sep 2020
First submitted
27 Apr 2016
Last updated
29 Sep 2020

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BI 836826 and Ibrutinib in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Boehringer Ingelheim at 3 sites in United States.

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 26 inclusion and 18 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: finished, as of the sponsor's last update on 29 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

Yes. Results are posted in the registry (first posted 24 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Recommended Phase 2 Dose of BI 836826 in Combination With Ibrutinib (time frame: First treatment cycle, 4 weeks from first administration of BI 836826.). 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 NCT02759016.

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 29 Sep 2020.

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