Study Stopped
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ERK 1/2 Signaling in Ibrutinib Resistant B-cell Malignancies
A Phase 1 Study Targeting ERK 1/2 Signaling in Ibrutinib Resistant B-cell Malignancies
1 other identifier
interventional
N/A
0 countries
N/A
Brief Summary
This research is studying the safety of combining ibrutinib with the study drug LY3214996 for chronic lymphocytic leukemia (CLL), Waldenstrom's macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL).
Trial Health
Trial Health Score
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Started Feb 2020
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 31, 2019
CompletedFirst Posted
Study publicly available on registry
August 2, 2019
CompletedStudy Start
First participant enrolled
February 3, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 3, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
February 3, 2020
CompletedFebruary 5, 2020
February 1, 2020
Same day
July 31, 2019
February 3, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Dose Limiting Toxicity
Toxicities occurring following administration of protocol therapy, measured using CTCAE 5.0 criteria.
42 days
Secondary Outcomes (2)
Best Response
From date of study drug initiation up to a maximum of 2 years
Time to Progression
From date of study drug initiation until the date of first documented progression or date of death from any cause, whichever comes first, up to a maximum of 2 years
Study Arms (1)
LY3214996+Ibrutinib
EXPERIMENTAL* LY3214996 will be administered by mouth once daily continuously throughout each treatment cycle * Ibrutinib will be administered by mouth once daily continuously throughout each treatment cycle.
Interventions
Ibrutinib inhibits the function of Bruton's tyrosine kinase (BTK). Ibrutinib blocks signals that stimulate malignant B cells to grow and divide uncontrollably.
LY3214996 is an extracellular signal-regulated kinase (ERK) inhibitor. ERK inhibitors stop the signal that a cancer cell receives telling it to grow.
Eligibility Criteria
You may qualify if:
- Participants must meet one of the following criteria:
- Clinicopathological diagnosis of Waldenstrom's macroglobulinemia (WM) meeting criteria for treatment using consensus panel guidelines from the Second International Workshop on Waldenstrom's Macroglobulinemia31 or have high risk disease with a serum IgM level of 6,000 mg or higher.32
- Confirmed diagnosis of chronic lymphocytic leukemia (CLL) per International Workshop on CLL 2018 criteria.33
- Histologically or cytologically confirmed diagnosis of mantle cell lymphoma (MCL) or marginal zone lymphoma (MZL).
- Participants must have a BTKCys481 and/or PLCγ2 mutation. Genomic alterations must have been confirmed via sequencing performed at NeoGenomics Laboratories.
- All participants must have experienced disease progression while actively receiving ibrutinib monotherapy based on National Comprehensive Cancer Network (NCCN) guidelines.
- All participants must be actively receiving ibrutinib monotherapy at the time of study entry. Participants with a gap in treatment or who received anti-cancer treatments other than ibrutinib immediately prior to study entry are not eligible.
- Participants must have been on a stable dose of ibrutinib monotherapy for a minimum of 3 weeks prior to cycle 1 day 1.
- Age ≥ 18 years.
- ECOG performance status ≤ 1 (see Appendix A)
- Participants must have measurable disease:
- Participants with WM: presence of serum immunoglobulin M (IgM) with a minimum IgM level of \> 2 × institutional upper limit of normal.
- Participants with CLL:
- Palpable or CT measurable lymphadenopathy ≥ 1.5 cm, AND/OR
- Lymphocytosis ≥ 5,000/μL, AND/OR
- +14 more criteria
You may not qualify if:
- Participants who have had major surgery within 4 weeks prior to the first dose of study medication.
- Participants who have previously received treatment with an ERK inhibitor, including but not limited to previous treatment with LY3214996.
- Participants with known CNS disease involvement should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to LY3214996 or ibrutinib.
- Individuals with a history of a different malignancy are ineligible with the following exceptions: individuals who have been treated and are disease-free for a minimum of 3 years prior to study enrollment, or individuals who are deemed by the treating investigator to be at low risk for disease recurrence. Additionally, individuals with the following cancers are eligible if diagnosed within the past 3 years: basal or squamous cell carcinomas of the skin, breast or cervical carcinomas in situ, and low risk prostate cancer that does not require treatment as judged by the treating investigator.
- Participants who are known at the time of trial enrollment to require concomitant therapy with strong or moderate CYP3A inhibitors or inducers. The use of strong or moderate CYP3A inhibitors or inducers is prohibited for the duration of trial treatment.
- Participants who are known at the time of trial enrollment to require concomitant therapy with sensitive substrates of CYP3A4 or drugs cleared by CYP3A4 that have a narrow therapeutic range. The use of these drugs is prohibited for the duration of trial treatment.
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because LY3214996 and ibrutinib are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with LY3214996 or ibrutinib, breastfeeding should be discontinued if the mother is treated with LY3214996 or ibrutinib. A negative serum pregnancy test is required for women of childbearing potential prior to the first dose of study medication.
- Participants who are known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B or C.
- Participants with a history or findings of central or branch retinal artery or venous occlusion with significant vision less, or other retinal diseases causing visual impairment
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Dana-Farber Cancer Institutelead
- Eli Lilly and Companycollaborator
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Steven Treon, MD, PhD
Dana-Farber Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
July 31, 2019
First Posted
August 2, 2019
Study Start
February 3, 2020
Primary Completion
February 3, 2020
Study Completion
February 3, 2020
Last Updated
February 5, 2020
Record last verified: 2020-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- BCH - Contact the Technology \& Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.