Non-GCB/ABC Diffuse Large B-Cell LymphomaPhase 2NCT05319028
Study of Mivavotinib (CB-659) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
A Phase 2 study testing Mivavotinib in people with Non-GCB/ABC Diffuse Large B-Cell Lymphoma and With and Without MyD88 and/or CD79B Mutations, run by Calithera Biosciences, Inc at 7 sites in United States.
Trial summary
Study CX-659-401 is a multicenter, open-label, phase 2 study of mivavotinib to evaluate the single-agent activity of mivavotinib in patients with relapsed/refractory non-GCB/ABC DLBCL, incorporating ctDNA-based next-generation sequencing (NGS) to identify DLBCL patients harboring MyD88 and/or CD79B mutations within… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Non-GCB/ABC Diffuse Large B-Cell Lymphoma, With and Without MyD88 and/or CD79B Mutations
- What is being tested?
- Mivavotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 7 sitesUnited States
- Study dates
- 23 Jun 2022to 24 Feb 2023
- Phase
- Phase 2
- 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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients aged 18 years or older
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
- Life expectancy of > 3 months
- Histologically confirmed de novo or transformed non-GCB DLBCL.
- Relapsed or refractory to ≥ 2 prior lines of chemotherapy based on standard of care
- Patients should not have failed more than 5 prior lines of therapy
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- Must have [18F]Fluorodeoxyglucose-positron emission tomography (FDG-PET)-avid measurable disease that meets the size criteria per International Working Group (IWG) criteria.
- Must have recovered from adverse events of prior anti-cancer therapy to severity ≤ Grade 1.
- Adequate organ function as assessed by laboratory values.
- If female of childbearing potential, agreement to use protocol specified contraception methods. If male, agreement to use an effective barrier method of contraception.
Who cannot join
- DLBCL with central nervous system (CNS) involvement with active brain or leptomeningeal disease
- Known human immunodeficiency (HIV; testing not required) or HIV-related malignancy
- Known hepatitis B surface antigen positive or known or active hepatitis C infection
- Prior autologous stem cell transplant (ASCT) or chimeric antigen receptor T-cell (CAR-T) cell infusion within 90 days of screening
- Prior allogeneic stem cell transplantation
- Unstable/inadequate cardiac function
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- Known gastrointestinal (GI) disease or GI procedure that interferes with swallowing/absorption of oral drug
- Major surgery within 14 days before the first dose of study drug
- Serious infection (bacterial/fungal/viral) requiring parenteral antibiotic/antiviral therapy for >5 days within 21 days prior to first dose of study drug
- Treatment with high-dose corticosteroids for anticancer purposes within 7 days before the first dose of mivavotinib.
- Use of medication known to be inhibitors or inducers of P-glycoprotein (P-gp) and/or Cytochrome P (CYP)3A
- Female patients who are pregnant, lactating or breastfeeding.
- Any radiation therapy within 3 weeks prior to first dose of study treatment.
- Systemic anticancer treatment within 3 weeks before first dose of study treatment
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Henry Ford Health
Detroit, Michigan, 48202
Northwestern University
Evanston, Illinois, 60208
The University of Texas, M. D. Anderson Cancer Center
Houston, Texas, 77030
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Toledo Clinic Cancer Center
Toledo, Ohio, 43623
About this study
Official title: A Phase 2 Study of Mivavotinib in Biomarker-Defined Subgroups of Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Study CX-659-401 is a multicenter, open-label, phase 2 study of mivavotinib to evaluate the single-agent activity of mivavotinib in patients with relapsed/refractory non-GCB/ABC DLBCL, incorporating ctDNA-based next-generation sequencing (NGS) to identify DLBCL patients harboring MyD88 and/or CD79B mutations within the study. This goal of this strategy is to evaluate its activity both in the cell-of-origin subgroup of non-GCB/ABC DLBCL and in the genetically defined subgroups of MyD88/CD79B-mutated and wild type DLBCL.
Read the detailed description
Approximately 50 patients will be randomized 1:1 to one of two dose/schedule cohorts: one with a continuous dosing schedule (100 mg QD) and one with an induction dosing schedule (120 mg QD x 14 days, then 80 mg QD starting Day 15). Patients will receive treatment with mivavotinib until disease progression, unacceptable toxicity, withdrawal of consent, or death.
- Being tested
- Mivavotinib
- Keywords
- Mivavotinib, DLBCL, MyD88, CD79b, non-GCB, ABC, NHL, CB-659, Relapsed/Refractory
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MivavotinibDrug
Also called CB-659
oral tablet
| Study group | Role | What they receive |
|---|---|---|
| Continuous Dosing Schedule | Experimental | Mivavotinib 100 mg once daily (QD) Receives: Drug: Mivavotinib |
| Induction Dosing Schedule | Experimental | Mivavotinib 120 mg QD for 14 days, then 80 mg QD starting Day 15 Receives: Drug: Mivavotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR) as assessed by an independent radiology review committee (IRC) according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).
Overall response is defined as a complete response (CR) or partial response (PR). ORR is the proportion of participants who have overall responses.
Measured: Start of treatment up to 21 months
Safety as measured by type, incidence, severity, seriousness, and study drug-relatedness of adverse events per Common Terminology Criteria for Adverse Events, version 5
Type, incidence, severity, seriousness, and study drug-relatedness of AEs assessed by CTCAE v5.0
Measured: Start of treatment up to 21 months
Secondary outcomes (3)
Duration of Response (DOR) Rate as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).
DOR per IRC. DOR will be calculated as the time between the first documentation of partial response (PR) or a complete response (CR) to the first documentation of progressive disease or death, whichever occurs first.
Measured: Start of treatment up to 21 months
Progression-Free Survival (PFS) as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).
PFS per IRC. PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the IRC or death from any cause, whichever occurs first.
Measured: Start of treatment up to 21 months
Complete Response (CR) Rate as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).
CR rate per IRC according to the 2014 IWG Lugano criteria (Cheson, 2014)
Measured: Start of treatment to 21 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2022
- Study start23 Jun 2022
- Primary completion24 Feb 2023
- Study completion24 Feb 2023
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-GCB/ABC Diffuse Large B-Cell LymphomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Calithera Biosciences, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05319028
- Sponsor's protocol ID
- CX-659-401
- Status last verified
- Mar 2023
- First submitted
- 1 Apr 2022
- Last updated
- 4 Apr 2023
- 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 4 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Mivavotinib in Biomarker-Defined Subgroups of Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
- ClinicalTrials.gov ID
- NCT05319028
- Acronym / sponsor ID
- CX-659-401
- Keywords
- Mivavotinib, DLBCL, MyD88, CD79b, non-GCB, ABC, NHL, CB-659
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Calithera Biosciences, IncIndustry (pharma, biotech, devices)
- Study start
- 23 Jun 2022 (actual)
- Primary completion
- 24 Feb 2023 (actual)
- Study completion
- 24 Feb 2023 (actual)
- First posted
- 8 Apr 2022 (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.
Study CX-659-401 is a multicenter, open-label, phase 2 study of mivavotinib to evaluate the single-agent activity of mivavotinib in patients with relapsed/refractory non-GCB/ABC DLBCL, incorporating ctDNA-based next-generation sequencing (NGS) to identify DLBCL patients harboring MyD88 and/or CD79B mutations within the study. This goal of this strategy is to evaluate its activity both in the cell-of-origin subgroup of non-GCB/ABC DLBCL and in the genetically defined subgroups of MyD88/CD79B-mutated and wild type DLBCL.
Detailed description
Approximately 50 patients will be randomized 1:1 to one of two dose/schedule cohorts: one with a continuous dosing schedule (100 mg QD) and one with an induction dosing schedule (120 mg QD x 14 days, then 80 mg QD starting Day 15). Patients will receive treatment with mivavotinib until disease progression, unacceptable toxicity, withdrawal of consent, or death.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continuous Dosing Schedule | Experimental | Drug: MivavotinibMivavotinib 100 mg once daily (QD) |
| Induction Dosing Schedule | Experimental | Drug: MivavotinibMivavotinib 120 mg QD for 14 days, then 80 mg QD starting Day 15 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female patients aged 18 years or older
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
- Life expectancy of > 3 months
- Histologically confirmed de novo or transformed non-GCB DLBCL.
- Relapsed or refractory to ≥ 2 prior lines of chemotherapy based on standard of care
Key exclusion criteria (14 listed)
- DLBCL with central nervous system (CNS) involvement with active brain or leptomeningeal disease
- Known human immunodeficiency (HIV; testing not required) or HIV-related malignancy
- Known hepatitis B surface antigen positive or known or active hepatitis C infection
- Prior autologous stem cell transplant (ASCT) or chimeric antigen receptor T-cell (CAR-T) cell infusion within 90 days of screening
- Prior allogeneic stem cell transplantation
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 |
|---|---|---|
| MivavotinibAlso: CB-659oral tablet | Drug | Continuous Dosing Schedule, Induction Dosing Schedule |
Primary outcome
Overall Response Rate (ORR) as assessed by an independent radiology review committee (IRC) according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).
Time frame: Start of treatment up to 21 months
Overall response is defined as a complete response (CR) or partial response (PR). ORR is the proportion of participants who have overall responses.
Safety as measured by type, incidence, severity, seriousness, and study drug-relatedness of adverse events per Common Terminology Criteria for Adverse Events, version 5
Time frame: Start of treatment up to 21 months
Type, incidence, severity, seriousness, and study drug-relatedness of AEs assessed by CTCAE v5.0
3 secondary outcomes
Duration of Response (DOR) Rate as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).
Time frame: Start of treatment up to 21 months
Progression-Free Survival (PFS) as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).
Time frame: Start of treatment up to 21 months
Complete Response (CR) Rate as assessed by an IRC according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014).
Time frame: Start of treatment to 21 months
Results and safety
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2023.
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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.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mivavotinib in people with Non-GCB/ABC Diffuse Large B-Cell Lymphoma and With and Without MyD88 and/or CD79B Mutations, run by Calithera Biosciences, Inc at 7 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 10 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 4 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 stopped early (reason given: Sponsor Decision). Results are not available in the source record.
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?
Overall Response Rate (ORR) as assessed by an independent radiology review committee (IRC) according to the 2014 International Working Group (IWG) Lugano Criteria (Cheson, 2014). (time frame: Start of treatment up to 21 months). The study lists 2 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 4 Apr 2023.