Lymphoma, Mantle-CellPhase 1NCT02419560
Optimal Dose Finding Study ABT-199 and Ibrutinib in MCL
A Phase 1 study testing ABT-199 and Ibrutinib Combination in people with Lymphoma, Mantle-Cell and Recurrent Lymphoma, Mantle-Cell, run by Craig Portell, MD at 4 sites in United States.
Trial summary
The purpose of this study is to determine the optimal dosing scheme for the combination of ibrutinib with ABT-199 for the treatment of relapsed or refractory mantle cell lymphoma (MCL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Mantle-Cell, Recurrent Lymphoma, Mantle-Cell
- What is being tested?
- ABT-199 and Ibrutinib Combination
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 4 sitesUnited States
- Study dates
- Apr 2015to May 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with Mantle Cell Lymphoma and has had at least one chemotherapy.
- Subjects must have measurable or evaluable disease.
- ECOG Performance Status of 0-2.
- Must be referred for treatment with ibrutinib.
- Must have adequate organ function.
Who cannot join
- Subject is pregnant.
- Prior malignancy (except nonmelanomatous skin cancer) unless disease free for a minimum of 2 years; non-invasive conditions such as carcinoma in situ of the breast, oral cavity, or cervix are all permissible.
- Known CNS lymphoma.
- Prior or current treatment with certain medications. Talk to Study Contact for specifics.
- Subject is at high risk for TLS.
- Subject has malabsorption syndrome or other condition which may affect an enteral route of administration.
Show all 11Show fewer
- Subject has known contraindication or allergy to both xanthine oxidase inhibitors and rasburicase.
- Significant history of heart disease.
- Subject has an active infection.
- Known active Hepatitis B or Hepatitis C.
- A serious uncontrolled medical disorder that in the opinion of the investigator would impair the ability of the subject to receive protocol therapy.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
University of Virginia
Charlottesville, Virginia, 22908
City of Hope
Duarte, California, 91010
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Multi-institution Phase I/Ib Study of Ibrutinib With ABT-199 in Relapsed/Refractory Mantle Cell Lymphoma
The purpose of this study is to determine the optimal dosing scheme for the combination of ibrutinib with ABT-199 for the treatment of relapsed or refractory mantle cell lymphoma (MCL).
Read the detailed description
This is a multi-center, study which will be open at up to 4 clinical sites. The purpose of this study is to determine the optimal dosing scheme for the combination of ibrutinib with ABT-199 for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The main criterion for eligibility is MCL with measurable disease which is relapsed or refractory to at least 1 chemotherapy-containing regimen and has not been previously treated with ibrutinib.
This dose finding study will use a continual reassessment method, which accounts for both toxicity and efficacy in combinations of agents, to determine the optimal combination of the approved treatment ibrutinib with the investigational agent ABT-199. This study will accrue patients in two stages. In the initial stage, subjects will be accrued to dosing cohorts of increasing dosages of ABT-199 in combination with ibrutinib. The modeling is initiated once 1 subject experiences a dose limiting toxicity (DLT). During the modeling stage, treatment assignments will be made based on model prediction.
Subjects will remain on treatment until progression or unacceptable toxicity, and will be monitored for safety during the treatment interval. Safety will be evaluated by incidence of adverse events and number of discontinuations due to AEs. Efficacy endpoints include Overall Response Rate (ORR), Complete Response Rate (CRR), minimal residual disease response rate, and survival (PFS and OS). The study will also include exploratory analysis of the gene expression pattern in subjects who progress on treatment.
- Being tested
- ABT-199 and Ibrutinib Combination
- Keywords
- Relapsed, Laboratory biomarker research, Pharmacologic study, Bruton's tyrosine kinase inhibitor, BCL-2 inhibitor
- Medical subject headings
- Lymphoma, Mantle-Cell, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ABT-199 and Ibrutinib CombinationDrug
Also called GDC-0199, venetoclax, PCI-32765
Both are administered orally once daily.
| Study group | Role | What they receive |
|---|---|---|
| ABT-199 and Ibrutinib Combination | Experimental | Participants will take ABT-199 (dose 100-400 mg) and Ibrutinib (dose 280-560 mg). Receives: Drug: ABT-199 and Ibrutinib Combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose Limiting Toxicities
Measured: 30 Days Following Start of Treatment
Secondary outcomes (5)
Incidence and Severity of Adverse Events
Measured: Through 30 Days Following the Last Treatment
Overall Response Rate
Measured: Every Year Until Death; an Average of 2 Years
Complete Response Rate
Measured: Every Year Until Death; an Average of 2 Years
Progression-Free Survival
Measured: Every Year Until Death; an Average of 2 Years
Overall Survival
Measured: Every Year Until Death; an Average of 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionMay 2021
- Study completionMay 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, Mantle-CellStudies 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
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Craig Portell, MD
- Sponsor type
- University, hospital or other
- Collaborators
- AbbVie
- Responsible party
- Sponsor-investigator, Craig Portell, MD, University of Virginia
- Investigators
- Craig A Portell, MD, Study chair, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02419560
- Sponsor's protocol ID
- 17983
- Other IDs
- ABT199-MCL-UVA-001
- Status last verified
- May 2022
- First submitted
- 6 Mar 2015
- Last updated
- 24 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jayappa KD, Tran B, Gordon VL, Morris C, Saha S, Farrington CC, O'Connor CM, Zawacki KP, Isaac KM, Kester M, Bender TP, Williams ME, Portell CA, Weber MJ, Narla G. PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis. J Clin Invest. 2023 Jul 3;133(13):e155938. doi: 10.1172/JCI155938.
PubMed 37166997Portell CA, Wages NA, Kahl BS, Budde LE, Chen RW, Cohen JB, Varhegyi NE, Petroni GR, Williams ME. Dose-finding study of ibrutinib and venetoclax in relapsed or refractory mantle cell lymphoma. Blood Adv. 2022 Mar 8;6(5):1490-1498. doi: 10.1182/bloodadvances.2021005357.
PubMed 34700344
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-institution Phase I/Ib Study of Ibrutinib With ABT-199 in Relapsed/Refractory Mantle Cell Lymphoma
- ClinicalTrials.gov ID
- NCT02419560
- Acronym / sponsor ID
- 17983
- Keywords
- Relapsed, Laboratory biomarker research, Pharmacologic study, Bruton's tyrosine kinase inhibitor, BCL-2 inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Craig Portell, MDUniversity, hospital or other
- Collaborators
- AbbVie
- Study start
- Apr 2015 (actual)
- Primary completion
- May 2021 (actual)
- Study completion
- May 2021 (actual)
- First posted
- 17 Apr 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.
The purpose of this study is to determine the optimal dosing scheme for the combination of ibrutinib with ABT-199 for the treatment of relapsed or refractory mantle cell lymphoma (MCL).
Detailed description
This is a multi-center, study which will be open at up to 4 clinical sites. The purpose of this study is to determine the optimal dosing scheme for the combination of ibrutinib with ABT-199 for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The main criterion for eligibility is MCL with measurable disease which is relapsed or refractory to at least 1 chemotherapy-containing regimen and has not been previously treated with ibrutinib.
This dose finding study will use a continual reassessment method, which accounts for both toxicity and efficacy in combinations of agents, to determine the optimal combination of the approved treatment ibrutinib with the investigational agent ABT-199. This study will accrue patients in two stages. In the initial stage, subjects will be accrued to dosing cohorts of increasing dosages of ABT-199 in combination with ibrutinib. The modeling is initiated once 1 subject experiences a dose limiting toxicity (DLT). During the modeling stage, treatment assignments will be made based on model prediction.
Subjects will remain on treatment until progression or unacceptable toxicity, and will be monitored for safety during the treatment interval. Safety will be evaluated by incidence of adverse events and number of discontinuations due to AEs. Efficacy endpoints include Overall Response Rate (ORR), Complete Response Rate (CRR), minimal residual disease response rate, and survival (PFS and OS). The study will also include exploratory analysis of the gene expression pattern in subjects who progress on treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ABT-199 and Ibrutinib Combination | Experimental | Drug: ABT-199 and Ibrutinib CombinationParticipants will take ABT-199 (dose 100-400 mg) and Ibrutinib (dose 280-560 mg). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosed with Mantle Cell Lymphoma and has had at least one chemotherapy.
- Subjects must have measurable or evaluable disease.
- ECOG Performance Status of 0-2.
- Must be referred for treatment with ibrutinib.
- Must have adequate organ function.
Key exclusion criteria (11 listed)
- Subject is pregnant.
- Prior malignancy (except nonmelanomatous skin cancer) unless disease free for a minimum of 2 years; non-invasive conditions such as carcinoma in situ of the breast, oral cavity, or cervix are all permissible.
- Known CNS lymphoma.
- Prior or current treatment with certain medications. Talk to Study Contact for specifics.
- Subject is at high risk for TLS.
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 |
|---|---|---|
| ABT-199 and Ibrutinib CombinationAlso: GDC-0199, venetoclax, PCI-32765Both are administered orally once daily. | Drug | ABT-199 and Ibrutinib Combination |
Primary outcome
Incidence of Dose Limiting Toxicities
Time frame: 30 Days Following Start of Treatment
5 secondary outcomes
Incidence and Severity of Adverse Events
Time frame: Through 30 Days Following the Last Treatment
Overall Response Rate
Time frame: Every Year Until Death; an Average of 2 Years
Complete Response Rate
Time frame: Every Year Until Death; an Average of 2 Years
Progression-Free Survival
Time frame: Every Year Until Death; an Average of 2 Years
Overall Survival
Time frame: Every Year Until Death; an Average of 2 Years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2022.
- Derived from this study: PubMed 37166997Jayappa KD, Tran B, Gordon VL, Morris C, Saha S, Farrington CC, O'Connor CM, Zawacki KP, Isaac KM, Kester M, Bender TP, Williams ME, Portell CA, Weber MJ, Narla G. PP2A modulation overcomes multidrug resistance in chronic lymphocytic leukemia via mPTP-dependent apoptosis. J Clin Invest. 2023 Jul 3;133(13):e155938. doi: 10.1172/JCI155938.
- Derived from this study: PubMed 34700344Portell CA, Wages NA, Kahl BS, Budde LE, Chen RW, Cohen JB, Varhegyi NE, Petroni GR, Williams ME. Dose-finding study of ibrutinib and venetoclax in relapsed or refractory mantle cell lymphoma. Blood Adv. 2022 Mar 8;6(5):1490-1498. doi: 10.1182/bloodadvances.2021005357.
Related trials for Lymphoma, Mantle-Cell
Active, not recruitingPhase 1/2
Study to Evaluate the Safety and Preliminary Efficacy of Ibrutinib and Pembrolizumab in Patients With Chronic Lymphocytic Leukemia (CLL) or Mantle Cell Lymphoma (MCL)
Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Sonrotoclax Plus Zanubrutinib Compared With Placebo Plus Zanubrutinib in Adults With Relapsed/Refractory Mantle Cell Lymphoma (CELESTIAL-RRMCL)
Mantle Cell Lymphoma, B Cell Lymphoma
RecruitingPhase 1
Phase Ib Clinical Study of Keynatinib
Lymphoma, B-Cell
RecruitingObservational study
Observational Study of Cardiac Arrhythmias During Treatment With BTK Inhibitors or Venetoclax
Chronic Lymphocytic Leukemia (CLL), Waldenstr(SqrRoot)(Delta)m s Macroglobulinemia
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia
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.
Craig A Portell, MD study chair
University of Virginia
4 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 ABT-199 and Ibrutinib Combination in people with Lymphoma, Mantle-Cell and Recurrent Lymphoma, Mantle-Cell, run by Craig Portell, MD at 4 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 5 inclusion and 11 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: finished, as of the sponsor's last update on 24 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of Dose Limiting Toxicities (time frame: 30 Days Following Start of Treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02419560, which also lists 2 linked publications.
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 24 May 2022.