Chronic Lymphocytic LeukemiaPhase 3NCT01980875
Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
A Phase 3 study testing Idelalisib, Chlorambucil and Obinutuzumab in people with Chronic Lymphocytic Leukemia, run by Gilead Sciences at 18 sites in 8 countries.
Trial summary
The primary objective of this study is to evaluate the effects of idelalisib with obinutuzumab versus the combination of chlorambucil and obinutuzumab on progression-free survival (PFS) in participants with previously untreated chronic lymphocytic leukemia (CLL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Idelalisib, Chlorambucil and Obinutuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 18 sitesin 8 countries
- Study dates
- 21 Apr 2015to 13 May 2016
- Phase
- Phase 3
- 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
- Not a candidate for fludarabine therapy based on either:
- creatinine clearance < 70 mL/min, or
- Cumulative Illness Rating Scale score > 6, by assessment of the investigator
- Diagnosis of B-cell CLL, with diagnosis established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL)
- No prior therapy for CLL other than corticosteroids for disease complications.
- CLL that warrants treatment
- Presence of measurable lymphadenopathy
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
Who cannot join
- Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
- Known presence of myelodysplastic syndrome
- Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of randomization
- Ongoing liver injury
- Ongoing drug-induced pneumonitis
- Ongoing inflammatory bowel disease
Show all 14Show fewer
- History of prior allogeneic bone marrow progenitor cell or solid organ transplantation
- Ongoing immunosuppressive therapy other than corticosteroids
- Concurrent participation in another therapeutic clinical trial
- Undergone major surgery within 30 days prior to randomization
- Known hypersensitivity or intolerance to any of the active substances or excipients in the formulations for idelalisib, obinutuzumab, or chlorambucil
- History of non-infectious pneumonitis
- Received last dose of study drug on another therapeutic clinical trial within 30 days prior to randomization
- Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
18 sites in 8 countries.
18 sites in 8 countries
United States6 sites
Gabrail Cancer Center Research
Canton, Ohio, 44718
Saint Francis Cancer Center
Greenville, South Carolina, 29607
Sansum Clinic
Santa Barbara, California, 93105
UCLA Jonsson Comprehensive Cancer Center
Santa Monica, California, 90404
Cancer Center of Central Connecticut
Southington, Connecticut, 06489
Innovative Clinical Research Institute
Whittier, California, 90603
Poland5 sites
Szpital Specjalistyczny w Brzozowie, Oddzial Hematologii Onkologicznej
Brzozów, Podkarpackie Voivodeship, 36-200
Malopolskie Centrum Medyczne s.c.
Krakow, 30-510
Wojewódzki Szpital Specjalistyczny w Legnicy
Legnica, 59-220
Wojewodzki Szpital Specjalistyczny, im. M. Kopernika Klinika Hematologii Uniwersytetu Medycznego
Lodz, 93-510
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa Spraw Wewnetrznych z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Hematologii
Olsztyn, 10-228
France2 sites
Centre Hospitalier du Mans
Le Mans, 72037
Centre Hospitalier de Perpignan
Perpignan, 66046-BP 49954
Australia1 site
St Vincent Hospital, Sydney
Darlinghurst, New South Wales, 2010
Canada1 site
Royal Victoria Regional Health Centre - Simcoe Musk
Barrie, Ontario, L4M 6M2
United Kingdom1 site
East Kent Hospitals University NHS Foundation Trust
Canterbury, Kent, CT1 3NG
About this study
Official title: A Phase 3, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
The primary objective of this study is to evaluate the effects of idelalisib with obinutuzumab versus the combination of chlorambucil and obinutuzumab on progression-free survival (PFS) in participants with previously untreated chronic lymphocytic leukemia (CLL).
An increased rate of deaths and serious adverse events (SAEs) among participants with front-line CLL and early-line indolent non-Hodgkin lymphoma (iNHL) treated with idelalisib in combination with standard therapies was observed by the independent data monitoring committee (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data and terminated those studies in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA). All front-line studies of idelalisib, including this study, were also terminated.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Idelalisib, Chlorambucil, Obinutuzumab
- 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®
150 mg tablet administered orally twice daily
ChlorambucilDrug
2 mg tablets administered at a dose of 0.5 mg/kg orally every other week for a total of 12 doses
ObinutuzumabDrug
1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks
| Study group | Role | What they receive |
|---|---|---|
| Safety Run-In: Idelalisib+obinutuzumab | Experimental | Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks. Following 4 weeks of treatment, safety data will be reviewed by an independent data monitoring committee (DMC). If acceptable tolerability is observed, the randomized portion of the study will begin. Receives: Drug: Idelalisib; Drug: Obinutuzumab |
| Randomized: Idelalisib+obinutuzumab | Experimental | Participants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks. Receives: Drug: Idelalisib; Drug: Obinutuzumab |
| Randomized: Obinutuzumab+chlorambucil | Active comparator | Participants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks. Receives: Drug: Chlorambucil; Drug: Obinutuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival
Progression-free survival (PFS) is defined as the interval from randomization to the first documentation of definitive disease progression or death from any cause. Definitive disease progression is CLL progression based on standard criteria, excluding lymphocytosis alone. PFS was to be assessed by an independent review committee (IRC).
Measured: Up to 11 months
Secondary outcomes (5)
Overall Response Rate
Overall response rate (ORR) is defined as the proportion of participants who achieve a confirmed complete or partial response. ORR was to be assessed by an IRC.
Measured: Up to 11 months
Nodal Response Rate
Nodal response rate is defined as the proportion of participants who achieve a 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters of index lesions. Nodal response rate was to be assessed by an IRC.
Measured: Up to 11 months
Complete Response Rate
Complete response rate is defined as the proportion of participants who achieve a confirmed complete response. Complete response rate was to be assessed by an IRC.
Measured: Up to 11 months
Overall Survival
Overall survival is defined as the interval from randomization to death from any cause. Overall survival was to be assessed by an IRC.
Measured: Up to 11 months
Minimal Residual Disease Negativity Rate at Week 36
Minimal residual disease (MRD) negativity rate is defined as the proportion of participants with MRD < 10^-4 assessed by flow cytometry in bone marrow at Week 36 after therapy initiation. For participants receiving the final dose of obinutuzumab after the original scheduled date, the MRD assessment was performed no less than 12 weeks after the last dose of obinutuzumab. MRD negativity rate was to be assessed by an IRC.
Measured: Up to 11 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2013 (estimated)
- Study start21 Apr 2015
- Primary completion13 May 2016
- Study completion13 May 2016
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 LeukemiaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Safety Run-In Phase: Single Group; Randomized Phase: Parallel
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01980875
- Sponsor's protocol ID
- GS-US-312-0118
- Other IDs
- 2013-004551-20
- Status last verified
- May 2017
- First submitted
- 5 Nov 2013
- Last updated
- 19 Nov 2018
- 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 http://www.gilead.com/research/disclosure-and-transparency.
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Idelalisib in Combination With Obinutuzumab Compared to Chlorambucil in Combination With Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT01980875
- Acronym / sponsor ID
- GS-US-312-0118
- Conditions
- Chronic Lymphocytic Leukemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 21 Apr 2015 (actual)
- Primary completion
- 13 May 2016 (actual)
- Study completion
- 13 May 2016 (actual)
- First posted
- 11 Nov 2013 (estimated)
- Results
- Posted 28 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the effects of idelalisib with obinutuzumab versus the combination of chlorambucil and obinutuzumab on progression-free survival (PFS) in participants with previously untreated chronic lymphocytic leukemia (CLL).
An increased rate of deaths and serious adverse events (SAEs) among participants with front-line CLL and early-line indolent non-Hodgkin lymphoma (iNHL) treated with idelalisib in combination with standard therapies was observed by the independent data monitoring committee (DMC) during regular review of 3 Gilead Phase 3 studies. Gilead reviewed the unblinded data and terminated those studies in agreement with the DMC recommendation and in consultation with the US Food and Drug Administration (FDA). All front-line studies of idelalisib, including this study, were also terminated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Safety Run-In Phase: Single Group; Randomized Phase: Parallel
| Arm | Type | Receives |
|---|---|---|
| Safety Run-In: Idelalisib+obinutuzumab | Experimental | Drug: Idelalisib, Drug: ObinutuzumabParticipants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks. Following 4 weeks of treatment, safety data will be reviewed by an independent data monitoring committee (DMC). If acceptable tolerability is observed, the randomized portion of the study will begin. |
| Randomized: Idelalisib+obinutuzumab | Experimental | Drug: Idelalisib, Drug: ObinutuzumabParticipants will receive idelalisib for 96 weeks and obinutuzumab over 21 weeks. |
| Randomized: Obinutuzumab+chlorambucil | Active comparator | Drug: Chlorambucil, Drug: ObinutuzumabParticipants will receive obinutuzumab over 21 weeks and chlorambucil over 23 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Not a candidate for fludarabine therapy based on either:
- Diagnosis of B-cell CLL, with diagnosis established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL)
- No prior therapy for CLL other than corticosteroids for disease complications.
- CLL that warrants treatment
- Presence of measurable lymphadenopathy
Key exclusion criteria (14 listed)
- Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation)
- Known presence of myelodysplastic syndrome
- Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of randomization
- Ongoing liver injury
- Ongoing drug-induced pneumonitis
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®150 mg tablet administered orally twice daily | Drug | Randomized: Idelalisib+obinutuzumab, Safety Run-In: Idelalisib+obinutuzumab |
| Chlorambucil2 mg tablets administered at a dose of 0.5 mg/kg orally every other week for a total of 12 doses | Drug | Randomized: Obinutuzumab+chlorambucil |
| Obinutuzumab1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks | Drug | Randomized: Idelalisib+obinutuzumab, Randomized: Obinutuzumab+chlorambucil, Safety Run-In: Idelalisib+obinutuzumab |
Primary outcome
Progression-Free Survival
Time frame: Up to 11 months
Progression-free survival (PFS) is defined as the interval from randomization to the first documentation of definitive disease progression or death from any cause. Definitive disease progression is CLL progression based on standard criteria, excluding lymphocytosis alone. PFS was to be assessed by an independent review committee (IRC).
5 secondary outcomes
Overall Response Rate
Time frame: Up to 11 months
Nodal Response Rate
Time frame: Up to 11 months
Complete Response Rate
Time frame: Up to 11 months
Overall Survival
Time frame: Up to 11 months
Minimal Residual Disease Negativity Rate at Week 36
Time frame: Up to 11 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2018.
- 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 http://www.gilead.com/research/disclosure-and-transparency.
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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
18 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Idelalisib, Chlorambucil and Obinutuzumab in people with Chronic Lymphocytic Leukemia, run by Gilead Sciences at 18 sites in 8 countries.
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 8 inclusion and 14 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 19 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Poland, France, Australia, Belgium and 3 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 28 Jun 2017). 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?
Progression-Free Survival (time frame: Up to 11 months). 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 19 Nov 2018.