Chronic Lymphocytic LeukemiaPhase 1NCT03422393
Venetoclax With High-dose Ibrutinib for CLL Progressing on Single Agent Ibrutinib
A Phase 1 study testing Venetoclax and Ibrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Michael Choi at 1 site in United States.
Trial summary
The purpose of the study is to investigate whether the combination of venetoclax and ibrutinib (administered up to 840 mg per day) might be useful for the treatment of CLL or SLL that is not responding or no longer responding to treatment with ibrutinib alone. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
- What is being tested?
- Venetoclax and Ibrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2018to Aug 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Clinical and phenotypic verification of B cell CLL or SLL and measurable disease.
- Prior therapy: Patients must have been receiving single agent ibrutinib therapy at the time of disease progression. Patient may have received other therapy in combination with ibrutinib earlier in their treatment course.
- Women of childbearing potential (not postmenopausal for at least one year or not surgically incapable of bearing children) must agree not to become pregnant for the duration of the study.
- Adequate hematologic, hepatic and renal function
Who cannot join
- Known CNS lymphoma or leukemia
- History of Richter's or prolymphocytic transformation.
- Primary ibrutinib resistance
- Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP)
- History of major surgery within 4 weeks prior to first dose on this study.
- History of prior malignancy, with the exception of adequately treated non-melanoma skin cancer, malignancies treated with curative intent and with no evidence of active disease for more than 3 years, or adequately treated cervical carcinoma in situ without current evidence of disease.
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- Active clinically significant cardiovascular disease or history of myocardial infarction within 6 months of first dose.
- Active hepatitis B or C infection.
- Known history of infection with human immunodeficiency virus (HIV).
- Unable to swallow capsules or disease significantly affecting gastrointestinal function.
- History of stroke or intracranial hemorrhage within 6 months of first dose.
- Requires anticoagulation with warfarin or other Vitamin K antagonists.
- Requires treatment with a strong cytochrome P(CYP)450 3A inhibitor.
- Pregnant or breast-feeding women
- Current infection requiring parenteral antibiotics.
- Active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification.
- Patients who require immediate cytoreduction due to high risk of tumor lysis syndrome (ie, absolute lymphocyte count greater than 100k/uL).
Trial locations and contacts
1 site in 1 country.
United States1 site
UC San Diego Moores Cancer Center
La Jolla, California, 92093
About this study
Official title: A Phase 1 Clinical Trial to Evaluate Venetoclax With High-dose Ibrutinib for the Treatment of Patients With Chronic Lymphocytic Leukemia With Progressive Disease on Single Agent Ibrutinib.
The purpose of the study is to investigate whether the combination of venetoclax and ibrutinib (administered up to 840 mg per day) might be useful for the treatment of CLL or SLL that is not responding or no longer responding to treatment with ibrutinib alone. The study will evaluate whether this regimen can reduce the amount of cancerous cells in your body. If you agree, you will receive ibrutinib at a dose of up to 840 mg a day by mouth, as well as venetoclax. Although both of these agents are approved by the FDA for the treatment of CLL or SLL, the combination and the dosing schedule of ibrutinib are considered experimental.
Read the detailed description
This is phase 1 study for patients with CLL or small lymphocytic lymphoma (SLL) experiencing disease progression on single ibrutinib. This study will evaluate the optimal ibrutinib dose (including doses higher than 420 mg) when combined with venetoclax
During the screening period, patients will continue on ibrutinib at their previous tolerated dose, unless required to stop (e.g.: by a preceding clinical trial).
On cycle 1, day 1, the dose of ibrutinib will be assigned based on the dose cohort. Patients in cohort 1 will receive ibrutinib 420 mg PO daily. Patients in cohort 2 will receive ibrutinib 560 mg PO daily. Cohort 3 will be 840 mg PO daily.
On cycle 1, day 1, patients will initiate venetoclax. The dose of venetoclax will ramp-up from 20 mg PO daily to 400 mg PO daily over a 5 week period.
The primary safety endpoint is determination of DLTs during the first 35 days (completion of dose ramp up). The primary efficacy endpoint of overall response rate will be assessed on approximately Cycle 7, Day 1.
Rationale: The optimal management of patients that progress on ibrutinib, including those with acquired Btk or PLCg2 mutations, is not determined. In other cancers, continued treatment with small molecule inhibitors beyond disease progression provides significant benefit, with additional agents or adjustments to ablate the resistant subclone. Venetoclax is approved for the treatment of patients with CLL, and is well-tolerated and effective in high-risk disease, and so is an appropriate agent for this trial.
- Being tested
- Venetoclax, Ibrutinib
- Keywords
- venetoclax, ibrutinib, high-dose ibrutinib, chronic lymphocytic leukemia, progressive disease, Small Lymphocytic Lymphoma, cancer
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Disease Progression, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VenetoclaxDrug
Also called Venclexta
On cycle 1, day 1, patients will initiate venetoclax. The dose of venetoclax will ramp-up from 20 mg PO daily to 400 mg PO daily over a 5 week period.
IbrutinibDrug
Also called Imbruvica
During the screening period, patients will continue on ibrutinib at their previous tolerated dose, unless required to stop (e.g.: by a preceding clinical trial).
On cycle 1, day 1, the dose of ibrutinib will be assigned based on the dose cohort. Patients in cohort 1 will receive ibrutinib 420 mg PO daily. Patients in cohort 2 will receive ibrutinib 560 mg PO daily. Cohort 3 will be 840 mg PO daily.
| Study group | Role | What they receive |
|---|---|---|
| venetoclax with high-dose ibrutinib | Experimental | venetoclax with high-dose ibrutinib for the treatment of patients with chronic lymphocytic leukemia with progressive disease on single agent ibrutinib. Receives: Drug: Venetoclax; Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose or biologically active dose.
Maximum tolerated dose or biologically active dose.
Measured: 1 year or more
Secondary outcomes (4)
Treatment-emergent adverse events
Treatment-emergent adverse events (description, timing, grade [CTCAE v4.03], severity, seriousness, and relatedness)
Measured: 2 years or more
Overall response rate
Partial Response, Partial Response with Lymphocytosis, and Complete Response) based on international working group guidelines. Best overall response will be determined
Measured: 2 years or more
Progression free survival rate at completion of combination therapy
Progression free survival rate at completion of combination therapy, duration of response, as determined by International Working Group in CLL (iwCLL) criteria.
Measured: 2 years or more
Stable disease rate
Stable disease rate (also based on 2008 iwCLL guidelines), also at the time of primary endpoint response assessment.
Measured: 2 years or more
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2018
- Study start1 May 2018
- Primary completionAug 2024 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Michael Choi
- Sponsor type
- University, hospital or other
- Collaborators
- Pharmacyclics LLC.
- Responsible party
- Sponsor-investigator, Michael Choi, University of California, San Diego
- Investigators
- Michael Choi, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03422393
- Sponsor's protocol ID
- 171613
- Status last verified
- Jul 2024
- First submitted
- 30 Jan 2018
- Last updated
- 5 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Clinical Trial to Evaluate Venetoclax With High-dose Ibrutinib for the Treatment of Patients With Chronic Lymphocytic Leukemia With Progressive Disease on Single Agent Ibrutinib.
- ClinicalTrials.gov ID
- NCT03422393
- Acronym / sponsor ID
- 171613
- Keywords
- venetoclax, ibrutinib, high-dose ibrutinib, chronic lymphocytic leukemia, progressive disease, Small Lymphocytic Lymphoma, cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Michael ChoiUniversity, hospital or other
- Collaborators
- Pharmacyclics LLC.
- Study start
- 1 May 2018 (actual)
- Primary completion
- Aug 2024 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 5 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to investigate whether the combination of venetoclax and ibrutinib (administered up to 840 mg per day) might be useful for the treatment of CLL or SLL that is not responding or no longer responding to treatment with ibrutinib alone. The study will evaluate whether this regimen can reduce the amount of cancerous cells in your body. If you agree, you will receive ibrutinib at a dose of up to 840 mg a day by mouth, as well as venetoclax. Although both of these agents are approved by the FDA for the treatment of CLL or SLL, the combination and the dosing schedule of ibrutinib are considered experimental.
Detailed description
This is phase 1 study for patients with CLL or small lymphocytic lymphoma (SLL) experiencing disease progression on single ibrutinib. This study will evaluate the optimal ibrutinib dose (including doses higher than 420 mg) when combined with venetoclax
During the screening period, patients will continue on ibrutinib at their previous tolerated dose, unless required to stop (e.g.: by a preceding clinical trial).
On cycle 1, day 1, the dose of ibrutinib will be assigned based on the dose cohort. Patients in cohort 1 will receive ibrutinib 420 mg PO daily. Patients in cohort 2 will receive ibrutinib 560 mg PO daily. Cohort 3 will be 840 mg PO daily.
On cycle 1, day 1, patients will initiate venetoclax. The dose of venetoclax will ramp-up from 20 mg PO daily to 400 mg PO daily over a 5 week period.
The primary safety endpoint is determination of DLTs during the first 35 days (completion of dose ramp up). The primary efficacy endpoint of overall response rate will be assessed on approximately Cycle 7, Day 1.
Rationale: The optimal management of patients that progress on ibrutinib, including those with acquired Btk or PLCg2 mutations, is not determined. In other cancers, continued treatment with small molecule inhibitors beyond disease progression provides significant benefit, with additional agents or adjustments to ablate the resistant subclone. Venetoclax is approved for the treatment of patients with CLL, and is well-tolerated and effective in high-risk disease, and so is an appropriate agent for this trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| venetoclax with high-dose ibrutinib | Experimental | Drug: Venetoclax, Drug: Ibrutinibvenetoclax with high-dose ibrutinib for the treatment of patients with chronic lymphocytic leukemia with progressive disease on single agent ibrutinib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Clinical and phenotypic verification of B cell CLL or SLL and measurable disease.
- Prior therapy: Patients must have been receiving single agent ibrutinib therapy at the time of disease progression. Patient may have received other therapy in combination with ibrutinib earlier in their treatment course.
- Women of childbearing potential (not postmenopausal for at least one year or not surgically incapable of bearing children) must agree not to become pregnant for the duration of the study.
- Adequate hematologic, hepatic and renal function
Key exclusion criteria (17 listed)
- Known CNS lymphoma or leukemia
- History of Richter's or prolymphocytic transformation.
- Primary ibrutinib resistance
- Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP)
- History of major surgery within 4 weeks prior to first dose on this study.
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 |
|---|---|---|
| VenetoclaxAlso: VenclextaOn cycle 1, day 1, patients will initiate venetoclax. The dose of venetoclax will ramp-up from 20 mg PO daily to 400 mg PO daily over a 5 week period. | Drug | venetoclax with high-dose ibrutinib |
| IbrutinibAlso: ImbruvicaDuring the screening period, patients will continue on ibrutinib at their previous tolerated dose, unless required to stop (e.g.: by a preceding clinical trial). On cycle 1, day 1, the dose of ibrutinib will be assigned based on the dose cohort. Patients in cohort 1 will receive ibrutinib 420 mg PO daily. Patients in cohort 2 will receive ibrutinib 560 mg PO daily. Cohort 3 will be 840 mg PO daily. | Drug | venetoclax with high-dose ibrutinib |
Primary outcome
Maximum tolerated dose or biologically active dose.
Time frame: 1 year or more
Maximum tolerated dose or biologically active dose.
4 secondary outcomes
Treatment-emergent adverse events
Time frame: 2 years or more
Overall response rate
Time frame: 2 years or more
Progression free survival rate at completion of combination therapy
Time frame: 2 years or more
Stable disease rate
Time frame: 2 years or more
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2024.
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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.
Michael Choi, MD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Venetoclax and Ibrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Michael Choi at 1 site 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 4 inclusion and 17 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: under way, not looking for participants, as of the sponsor's last update on 5 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
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 or biologically active dose. (time frame: 1 year or more). 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 5 Jul 2024.