Chronic Lymphocytic Leukemia (CLL)Phase 1NCT02538614
Study of Idelalisib in Combination With BI 836826 in Participants With Chronic Lymphocytic Leukemia
A Phase 1 study testing Idelalisib and BI 836826 in people with Chronic Lymphocytic Leukemia (CLL), run by Gilead Sciences at 2 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia (CLL)
- What is being tested?
- Idelalisib and BI 836826
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- 29 Dec 2015to 5 Jul 2017
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ohio State University
Columbus, Ohio
University of Utah
Salt Lake City, Utah
About this study
Official title: 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.
- Conditions
- Chronic Lymphocytic Leukemia (CLL)
- Being tested
- Idelalisib, 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.
IdelalisibDrug
Also called GS-1101, CAL-101, Zydelig®
Tablets administered orally twice daily
BI 836826Drug
Intravenous administration as a rate-controlled infusion
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b: Idelalisib + BI 836826 | Experimental | 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. Receives: Drug: Idelalisib; Drug: BI 836826 |
| Phase 2 Idelalisib + BI 836826 | Experimental | Participants will be randomly assigned to receive 1 of the 2 dose combinations selected from Phase 1b. Receives: Drug: Idelalisib; Drug: BI 836826 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1b: Percentage of Participants Experienced Dose Limiting Toxicities (DLTs) During the First 7 Weeks of Study Therapy
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.
Measured: Up to 7 weeks
For Phase 2: Complete Response Rate (CRR)
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.
Measured: Up to 18 months
For Phase 2: Minimal Residual Disease (MRD) Negativity Rate in Bone Marrow by Week 50
MRD defined as the percentage of participants with MRD < 10^-4, assessed by flow cytometry in bone marrow, achieved by Week 50.
Measured: Week 50
Secondary outcomes (10)
Phase 1b: Percentage of Participants Experienced DLTs During the Treatment Period
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.
Measured: Up to 18 months
For Phase 1b and Phase 2: Number of Participants Experiencing Any Serious Adverse Events (SAE)
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.
Measured: Up to 18 months
For Phase 1b and Phase 2: Number of Participants Who Permanently Discontinued Study Treatment Due to an Adverse Event
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.
Measured: Up to 18 months
For Phase 2: Overall Response Rate (ORR)
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.
Measured: Up to 18 months
For Phase 2: Duration of Complete Response (DCR)
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.
Measured: Up to 18 months
For Phase 2: Duration of Response (DOR)
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.
Measured: Up to 18 months
For Phase 2: Progression-Free Survival (PFS)
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.
Measured: Up to 18 months
For Phase 2: Overall Survival (OS)
OS was defined as the interval from the randomization to the date of death from any cause.
Measured: Up to 18 months
For Phase 2: MRD Negativity Rate in Blood at Any Time
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.
Measured: Up to 18 months
For Phase 2: MRD Negativity Rate in Bone Marrow at Any Time
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.
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2015 (estimated)
- Study start29 Dec 2015
- Primary completion5 Jul 2017
- Study completion5 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Lymphocytic Leukemia (CLL)Studies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Phase 1b: sequential assignment, Phase 2: parallel assignment
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Boehringer Ingelheim
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02538614
- Sponsor's protocol ID
- GS-US-312-1579
- Status last verified
- Nov 2020
- First submitted
- 31 Aug 2015
- Last updated
- 25 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Study of Idelalisib in Combination With BI 836826 in Subjects With Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT02538614
- Acronym / sponsor ID
- GS-US-312-1579
- Conditions
- Chronic Lymphocytic Leukemia (CLL)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Collaborators
- Boehringer Ingelheim
- Study start
- 29 Dec 2015 (actual)
- Primary completion
- 5 Jul 2017 (actual)
- Study completion
- 5 Jul 2017 (actual)
- First posted
- 2 Sep 2015 (estimated)
- Results
- Posted 25 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase 1b: sequential assignment, Phase 2: parallel assignment
| Arm | Type | Receives |
|---|---|---|
| Phase 1b: Idelalisib + BI 836826 | Experimental | Drug: Idelalisib, Drug: BI 836826Participants 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. |
| Phase 2 Idelalisib + BI 836826 | Experimental | Drug: Idelalisib, Drug: BI 836826Participants will be randomly assigned to receive 1 of the 2 dose combinations selected from Phase 1b. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- 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 (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IdelalisibAlso: GS-1101, CAL-101, Zydelig®Tablets administered orally twice daily | Drug | Phase 1b: Idelalisib + BI 836826, Phase 2 Idelalisib + BI 836826 |
| BI 836826Intravenous administration as a rate-controlled infusion | Drug | Phase 1b: Idelalisib + BI 836826, Phase 2 Idelalisib + BI 836826 |
Primary outcome
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.
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.
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.
10 secondary outcomes
Phase 1b: Percentage of Participants Experienced DLTs During the Treatment Period
Time frame: 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
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
For Phase 2: Overall Response Rate (ORR)
Time frame: Up to 18 months
For Phase 2: Duration of Complete Response (DCR)
Time frame: Up to 18 months
For Phase 2: Duration of Response (DOR)
Time frame: Up to 18 months
For Phase 2: Progression-Free Survival (PFS)
Time frame: Up to 18 months
For Phase 2: Overall Survival (OS)
Time frame: Up to 18 months
For Phase 2: MRD Negativity Rate in Blood at Any Time
Time frame: Up to 18 months
For Phase 2: MRD Negativity Rate in Bone Marrow at Any Time
Time frame: Up to 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Idelalisib and BI 836826 in people with Chronic Lymphocytic Leukemia (CLL), run by Gilead Sciences at 2 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 9 inclusion and 13 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: stopped early, as of the sponsor's last update on 25 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 25 Nov 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?
Phase 1b: Percentage of Participants Experienced Dose Limiting Toxicities (DLTs) During the First 7 Weeks of Study Therapy (time frame: Up to 7 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Nov 2020.