Study of Idelalisib in Combination With BI 836826 in Participants With Chronic Lymphocytic Leukemia

November 23, 2020 updated by: Gilead Sciences

A Phase 1b/2 Study of Idelalisib in Combination With BI 836826 in Subjects With Chronic Lymphocytic Leukemia

This study consists of 2 parts: Phase 1b and Phase 2. Phase 1b will evaluate the safety and tolerability of the combination of idelallisib with the anti-CD37 monoclonal antibody BI 836826 in participants with relapsed/refractory chronic lymphocytic leukemia (R/R CLL), and establish the high recommended Phase 2 combination dose (highRP2D) as well as an alternate lower recommended Phase 2 combination dose (lowRP2D). Phase 2 will determine the rates of complete response (CR) and of minimal residual disease (MRD) negativity with the combination at the highRP2D and the lowRP2D in participants with R/R CLL.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States
        • Ohio State University
    • Utah
      • Salt Lake City, Utah, United States
        • University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • Diagnosis of B-cell CLL, established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and having received at least 2 prior treatment regimens
  • CLL that warrants treatment

  • Clinically quantifiable disease burden defined as:

    • For Phase 1b individuals: absolute lymphocyte count (ALC) > 5000/μL in peripheral blood.

    • For Phase 2 individuals either:

      • At least 1 node ≥ 2 cm on computed tomography (CT) or magnetic resonance imaging (MRI) or
      • bone marrow exam is performed at screening and demonstrates quantifiable CLL.
  • Discontinuation of all cytotoxic chemotherapy and anti-CD20 antibody therapy for ≥ 4 weeks, alemtuzumab for ≥ 8 weeks, targeted therapy for ≥ 2 weeks, and investigational therapy for ≥ 3 weeks before enrollment (Phase 1b) or randomization (Phase 2). For individuals with relapsed CLL most recently treated with B-cell receptor (BCR) pathway inhibitors who, in the opinion of the investigator, will not tolerate waiting 3 weeks, a washout period of > 5 half-lives is allowed. If on a systemic corticosteroid, the dose must be stable for the previous 4 weeks.
  • Eastern Cooperative Oncology Group (ECOG) score of ≤ 2

Key Exclusion Criteria:

  • Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
  • Known presence of myelodysplastic 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 enrollment, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 2 years.
  • Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of enrollment
  • Ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
  • History of drug-induced pneumonitis
  • Ongoing inflammatory bowel disease
  • Ongoing alcohol or drug addiction
  • History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
  • Ongoing systemic immunosuppressive therapy other than corticosteroids
  • History of prior therapy with any phosphatidylinositol 3-kinase (PI3K) inhibitor (including idelalisib), or any anti-CD37 agent
  • Ongoing infection with, or treatment or prophylaxis for, CMV within the past 28 days.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Phase 1b: Idelalisib + BI 836826
Participants will receive escalating dose of idelalisib at dose levels, 50 mg, 100 mg, and 150 mg + BI 836826 10 mg on Day 8, 50 mg on Day 9 and Day 15, and 100 mg on Day 22, every 2 weeks through Week 18, and every 4 weeks through Week 46. 2 dose combinations (highRP2D and lowRP2D) will be determined for further evaluations in Phase 2.
Drug: Idelalisib
Tablets administered orally twice daily
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101
Drug: BI 836826
Intravenous administration as a rate-controlled infusion
Experimental: Phase 2 Idelalisib + BI 836826
Participants will be randomly assigned to receive 1 of the 2 dose combinations selected from Phase 1b.
Drug: Idelalisib
Tablets administered orally twice daily
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101
Drug: BI 836826
Intravenous administration as a rate-controlled infusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Phase 1b: Percentage of Participants Experienced Dose Limiting Toxicities (DLTs) During the First 7 Weeks of Study Therapy
Time Frame: Up to 7 weeks
DLTs refer to toxicities experienced during the final 6 weeks of 7-week study treatment that have been judged to be clinically significant and related to study treatment. Events occurring during the initial 7-day idelalisib monotherapy run-in period and resolving by Day 8 were not included.
Up to 7 weeks
For Phase 2: Complete Response Rate (CRR)
Time Frame: Up to 18 months
CRR was defined as the percentage of participants who achieve a complete response (CR). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease.
Up to 18 months
For Phase 2: Minimal Residual Disease (MRD) Negativity Rate in Bone Marrow by Week 50
Time Frame: Week 50
MRD defined as the percentage of participants with MRD < 10^-4, assessed by flow cytometry in bone marrow, achieved by Week 50.
Week 50

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase 1b: Percentage of Participants Experienced DLTs During the Treatment Period
Time Frame: Up to 18 months
DLTs refer to toxicities experienced during the final 6 weeks of 7-week study treatment that have been judged to be clinically significant and related to study treatment. Events occurring during the initial 7-day idelalisib monotherapy run-in period and resolving by Day 8 were not included.
Up to 18 months
For Phase 1b and Phase 2: Number of Participants Experiencing Any Serious Adverse Events (SAE)
Time Frame: Up to 18 months
An SAE is defined as an event that, at any dose, results in the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction.
Up to 18 months
For Phase 1b and Phase 2: Number of Participants Who Permanently Discontinued Study Treatment Due to an Adverse Event
Time Frame: Up to 18 months
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
Up to 18 months
For Phase 2: Overall Response Rate (ORR)
Time Frame: Up to 18 months
ORR was defined as the percentage of participants achieving a complete response (CR) or partial response (PR). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions.
Up to 18 months
For Phase 2: Duration of Complete Response (DCR)
Time Frame: Up to 18 months
DCR was defined as the interval from the first documentation of CR to the earlier of the first documentation of definitive disease progression or death from any cause. CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease.
Up to 18 months
For Phase 2: Duration of Response (DOR)
Time Frame: Up to 18 months
DOR was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause. CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of the longest perpendicular diameters of all index lesions, with no new lesions.
Up to 18 months
For Phase 2: Progression-Free Survival (PFS)
Time Frame: Up to 18 months
PFS was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. Definitive disease progression was defined as evidence of any new disease, worsening of index lesions, spleen or liver, or non-index disease, decrease in platelet count or hemoglobin that is attributable to chronic lymphocytic leukemia (CLL) or more than 4 weeks after the discontinuation of idelalisib: an increase in the number of blood lymphocytes by 50% or more.
Up to 18 months
For Phase 2: Overall Survival (OS)
Time Frame: Up to 18 months
OS was defined as the interval from the randomization to the date of death from any cause.
Up to 18 months
For Phase 2: MRD Negativity Rate in Blood at Any Time
Time Frame: Up to 18 months
MRD negativity rate in blood was defined as the percentage of participants with MRD < 10^-4, assessed by flow cytometry in blood, at any time on study.
Up to 18 months
For Phase 2: MRD Negativity Rate in Bone Marrow at Any Time
Time Frame: Up to 18 months
MRD negativity rate in bone marrow was defined as the percentage of participants with MRD < 10^-4, assessed by flow cytometry in bone marrow, at any time on study.
Up to 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Gilead Sciences

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Boehringer Ingelheim

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 29, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 5, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 5, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 31, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 31, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 2, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 25, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 23, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GS-US-312-1579

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

IPD Sharing Time Frame

18 months after study completion

IPD Sharing Access Criteria

A secured external environment with username, password, and RSA code.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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