Chronic Lymphocytic LeukemiaPhase 1NCT02640833
A Study of Duvelisib and Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Indolent or Aggressive Non-Hodgkin Lymphoma, Who Have Not Previously Received a Bcl-2 or PI3K Inhibitor
A Phase 1 study testing Duvelisib and Venetoclax in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by AbbVie at 10 sites in United States.
Trial summary
This study is designed to assess the safety, pharmacokinetics, drug-drug interactions, and determine the recommended Phase 2 doses of co administered Duvelisib and Venetoclax in participants with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, or indolent or aggressive… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Non-Hodgkin Lymphoma
- What is being tested?
- Duvelisib and Venetoclax
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 10 sitesUnited States
- Study dates
- Jul 2016to Feb 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Subject must have either • Relapsed or refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (for Waves 2 or 3)
- Subject has evaluable disease and requires treatment in the opinion of the investigator.
- Subject must have relapsed following or be refractory to ≥ 1 standard treatments such as fludarabine based regimens (F, FC, FR, FCR), alkylator (chlorambucil, bendamustine) based regimens, or Bruton's Tyrosine Kinase inhibitor (Ibrutinib).
- Or
- Relapsed or refractory indolent Non-Hodgkin Lymphoma or aggressive Non-Hodgkin Lymphoma (for Waves 1, 2, or 3, unless otherwise indicated)
- Subject must have histologically documented diagnosis of a Follicular Lymphoma or Marginal Zone Lymphoma.
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- Subject must have histologically documented diagnosis of a Diffuse Large B-cell Lymphoma (excluding Richter's Transformation), Non-cutaneous T-Cell Lymphoma, or Mantle Cell Lymphoma (MCL) (MCL Wave 3 only)
- Subject has evaluable disease and requires treatment in the opinion of the investigator.
- Subject must have relapsed following or be refractory to ≥ 1 standard treatments such as R-CHOP, R-CVP, bendamustine, lenalidomide-rituximab, or fludarabine-based regimens.
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
- Subject must have adequate bone marrow independent of growth factor support per local laboratory reference range at Screening.
- Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening.
- NHL subjects who have a history of an autologous stem cell transplant (e.g., bone marrow) must be > 6 months post-transplant (prior to the first dose of study drug) and must not require any growth factor support.
Who cannot join
- Subject has been previously treated with a Bcl-2 or PI3K inhibitor.
- Subject is a candidate to receive another second-line therapy approved for usage by the local Health Authority.
- Subject is appropriate for a stem cell transplant or has undergone an allogeneic stem cell transplant.
- Subject has received any of the following within 14 days or 5 drug half-lives (whichever is shortest) prior to the first dose of duvelisib or venetoclax, or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
- Any anti-cancer therapy including chemotherapy or radiotherapy;
- Investigational therapy, including targeted small molecule agents.
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- Subject has received biologic agents (e.g., monoclonal antibodies) for anti-neoplastic treatment within 30 days prior to first dose of duvelisib or venetoclax.
- Subject has received live or live attenuated vaccines within 6 weeks prior to first dose of duvelisib or venetoclax.
- Subject has received the following within 7 days prior to the first dose of duvelisib or venetoclax:
- Steroid therapy for anti-neoplastic treatment;
- Strong and Moderate CYP3A inhibitors;
- Strong and Moderate CYP3A inducers;
- Chronic immunosuppressants, other than corticosteroids given at daily dose < 20 mg prednisone equivalent for ITP or AIHA.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Site Reference ID/Investigator# 145674
Baltimore, Maryland, 21287
Site Reference ID/Investigator# 145145
Boston, Massachusetts, 02215
Site Reference ID/Investigator# 147922
Chicago, Illinois, 60611
Site Reference ID/Investigator# 148010
Detroit, Michigan, 48202
Site Reference ID/Investigator# 148561
Goshen, Indiana, 46526
Site Reference ID/Investigator# 148559
Greenville, South Carolina, 29605
Site Reference ID/Investigator# 148562
Harvey, Illinois, 60426
Site Reference ID/Investigator# 145146
Lebanon, New Hampshire, 03756
Site Reference ID/Investigator# 147747
St Louis, Missouri, 63110
Site Reference ID/Investigator# 145677
Tucson, Arizona, 85724-5024
About this study
Official title: A Phase 1b/2 Study of Duvelisib and Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Indolent or Aggressive Non-Hodgkin Lymphoma, Who Have Not Previously Received a Bcl-2 or PI3K Inhibitor
This study is designed to assess the safety, pharmacokinetics, drug-drug interactions, and determine the recommended Phase 2 doses of co administered Duvelisib and Venetoclax in participants with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, or indolent or aggressive non-Hodgkin lymphoma, who have not previously received a Bcl-2 or Phosphoinositide 3-kinase (PI3K) inhibitor. The Phase 2 portion of the study will preliminarily evaluate efficacy, and expand the toxicity evaluation.
- Being tested
- Duvelisib, Venetoclax
- Keywords
- Refractory Lymphoma, Relapsed Leukemia
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Non-Hodgkin, Lymphoma, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DuvelisibDrug
Duvelisib will be taken continuously. This is a defining dose study, therefore the dose of Duvelisib may change.
VenetoclaxDrug
Venetoclax will be taken continuously. This is a defining dose study, therefore the dose of Venetoclax will change.
| Study group | Role | What they receive |
|---|---|---|
| Duvelisib+Venetoclax | Experimental | Not described Receives: Drug: Duvelisib; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events
Participants will be monitored for clinical and laboratory evidence of adverse events throughout the study.
Measured: From participant's first dose until 30 days after participant's last dose of study drug; up to 2 years following last participant first dose
Maximum observed plasma concentration (Cmax) of duvelisib
The highest concentration that a drug achieves in the blood after administration in a dosing interval.
Measured: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels.
Maximum observed plasma concentration (Cmax) of venetoclax
The highest concentration that a drug achieves in the blood after administration in a dosing interval.
Measured: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10, 12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels.
Time to maximum observed plasma concentration (Tmax) of duvelisib
The time at which the maximum plasma concentration (Cmax) is observed.
Measured: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels.
Time to maximum observed plasma concentration (Tmax) of venetoclax
The time at which the maximum plasma concentration (Cmax) is observed.
Measured: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10,12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels.
Area under the plasma concentration-time curve from time 0 to 12 hours post-dose (AUC12) of duvelisib
The area under the plasma concentration-time curve over a 12-hour dose interval
Measured: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels.
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC24) of venetoclax
The area under the plasma concentration-time curve over a 24-hour dose interval
Measured: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10,12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels.
Recommended phase two dose (RPTD) of Duvelisib in combination with venetoclax
Measured: Minimum first cycle of dosing (28 days)
Recommended phase two dose (RPTD) of Venetoclax in combination with duvelisib
Measured: Minimum first cycle of dosing (28 days)
Secondary outcomes (4)
Progression-free survival (PFS)
Progression-free survival will be defined as the number of days from the date of study drug start to the date of documented disease progression, relapse of death due to any cause whichever occurs first.
Measured: Measured up to 2 years after the last participant has enrolled in the study
Overall Response Rate (ORR)
Overall response rate will be defined as the proportion of participants who achieve a partial remission or better.
Measured: Measured up to 2 years after the last participant has enrolled in the study
Time to Tumor Progression (TTP)
Time to tumor progression is defined as the number of days from the date of study drug start to the date of the first documented disease progression or relapse.
Measured: Measured up to 2 years after the last participant has enrolled in the study
Duration of Response (DOR)
Duration of response is defined as the number of days from the date of documented first response of partial remission or better to the date of documented disease progression/relapse or death due to the disease whichever occurs first
Measured: Measured up to 2 years after the last participant has enrolled in the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2015 (estimated)
- Study startJul 2016
- Primary completionJan 2020 (estimated)
- Study completionFeb 2021 (estimated)
Why it stopped: Study Stopped
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.
- More trials run by AbbVieThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Infinity Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- John Hayslip, MD, Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02640833
- Sponsor's protocol ID
- M15-330
- Other IDs
- 2015-003302-16, 2015
- Status last verified
- Jul 2016
- First submitted
- 23 Dec 2015
- Last updated
- 26 Jul 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Study of Duvelisib and Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Indolent or Aggressive Non-Hodgkin Lymphoma, Who Have Not Previously Received a Bcl-2 or PI3K Inhibitor
- ClinicalTrials.gov ID
- NCT02640833
- Acronym / sponsor ID
- M15-330
- Keywords
- Refractory Lymphoma, Relapsed Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study Stopped
- Enrolment
- 0 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Collaborators
- Infinity Pharmaceuticals, Inc.
- Study start
- Jul 2016
- Primary completion
- Jan 2020 (estimated)
- Study completion
- Feb 2021 (estimated)
- First posted
- 29 Dec 2015 (estimated)
- 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.
This study is designed to assess the safety, pharmacokinetics, drug-drug interactions, and determine the recommended Phase 2 doses of co administered Duvelisib and Venetoclax in participants with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, or indolent or aggressive non-Hodgkin lymphoma, who have not previously received a Bcl-2 or Phosphoinositide 3-kinase (PI3K) inhibitor. The Phase 2 portion of the study will preliminarily evaluate efficacy, and expand the toxicity evaluation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Duvelisib+Venetoclax | Experimental | Drug: Duvelisib, Drug: Venetoclax |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Subject must have either • Relapsed or refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (for Waves 2 or 3)
- Subject has evaluable disease and requires treatment in the opinion of the investigator.
- Subject must have relapsed following or be refractory to ≥ 1 standard treatments such as fludarabine based regimens (F, FC, FR, FCR), alkylator (chlorambucil, bendamustine) based regimens, or Bruton's Tyrosine Kinase inhibitor (Ibrutinib).
- Or
- Relapsed or refractory indolent Non-Hodgkin Lymphoma or aggressive Non-Hodgkin Lymphoma (for Waves 1, 2, or 3, unless otherwise indicated)
Key exclusion criteria (13 listed)
- Subject has been previously treated with a Bcl-2 or PI3K inhibitor.
- Subject is a candidate to receive another second-line therapy approved for usage by the local Health Authority.
- Subject is appropriate for a stem cell transplant or has undergone an allogeneic stem cell transplant.
- Subject has received any of the following within 14 days or 5 drug half-lives (whichever is shortest) prior to the first dose of duvelisib or venetoclax, or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:
- Subject has received biologic agents (e.g., monoclonal antibodies) for anti-neoplastic treatment within 30 days prior to first dose of duvelisib or venetoclax.
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 |
|---|---|---|
| DuvelisibDuvelisib will be taken continuously. This is a defining dose study, therefore the dose of Duvelisib may change. | Drug | Duvelisib+Venetoclax |
| VenetoclaxVenetoclax will be taken continuously. This is a defining dose study, therefore the dose of Venetoclax will change. | Drug | Duvelisib+Venetoclax |
Primary outcome
Number of participants with adverse events
Time frame: From participant's first dose until 30 days after participant's last dose of study drug; up to 2 years following last participant first dose
Participants will be monitored for clinical and laboratory evidence of adverse events throughout the study.
Maximum observed plasma concentration (Cmax) of duvelisib
Time frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels.
The highest concentration that a drug achieves in the blood after administration in a dosing interval.
Maximum observed plasma concentration (Cmax) of venetoclax
Time frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10, 12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels.
The highest concentration that a drug achieves in the blood after administration in a dosing interval.
Time to maximum observed plasma concentration (Tmax) of duvelisib
Time frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels.
The time at which the maximum plasma concentration (Cmax) is observed.
Time to maximum observed plasma concentration (Tmax) of venetoclax
Time frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10,12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels.
The time at which the maximum plasma concentration (Cmax) is observed.
Area under the plasma concentration-time curve from time 0 to 12 hours post-dose (AUC12) of duvelisib
Time frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10 and 12 hours post-dose on Cycle 1 Day 14 and Day 22 for second and third dose levels.
The area under the plasma concentration-time curve over a 12-hour dose interval
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC24) of venetoclax
Time frame: Blood samples will be taken at 0 (pre-dose) 1,2,4,6,8,10,12 and 24 hours post-dose on Cycle 1 Days 7 and 14, and Day 22 for second and third dose levels.
The area under the plasma concentration-time curve over a 24-hour dose interval
Recommended phase two dose (RPTD) of Duvelisib in combination with venetoclax
Time frame: Minimum first cycle of dosing (28 days)
Recommended phase two dose (RPTD) of Venetoclax in combination with duvelisib
Time frame: Minimum first cycle of dosing (28 days)
4 secondary outcomes
Progression-free survival (PFS)
Time frame: Measured up to 2 years after the last participant has enrolled in the study
Overall Response Rate (ORR)
Time frame: Measured up to 2 years after the last participant has enrolled in the study
Time to Tumor Progression (TTP)
Time frame: Measured up to 2 years after the last participant has enrolled in the study
Duration of Response (DOR)
Time frame: Measured up to 2 years after the last participant has enrolled in the study
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2016.
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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.
John Hayslip, MD study director
AbbVie
10 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 Duvelisib and Venetoclax in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by AbbVie at 10 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 13 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: withdrawn, as of the sponsor's last update on 26 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of participants with adverse events (time frame: From participant's first dose until 30 days after participant's last dose of study drug; up to 2 years following last participant first dose). The study lists 9 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 26 Jul 2016.