Study of Mivavotinib (CB-659) in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

March 31, 2023 updated by: Calithera Biosciences, Inc

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Illinois
      • Evanston, Illinois, United States, 60208
        • Northwestern University
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center
      • Toledo, Ohio, United States, 43623
        • Toledo Clinic Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas, M. D. Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • The University of Texas Health Science Center at San Antonio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female patients aged 18 years or older
  2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
  3. Life expectancy of > 3 months
  4. Histologically confirmed de novo or transformed non-GCB DLBCL.
  5. Relapsed or refractory to ≥ 2 prior lines of chemotherapy based on standard of care
  6. Patients should not have failed more than 5 prior lines of therapy
  7. Must have [18F]Fluorodeoxyglucose-positron emission tomography (FDG-PET)-avid measurable disease that meets the size criteria per International Working Group (IWG) criteria.
  8. Must have recovered from adverse events of prior anti-cancer therapy to severity ≤ Grade 1.
  9. Adequate organ function as assessed by laboratory values.
  10. If female of childbearing potential, agreement to use protocol specified contraception methods. If male, agreement to use an effective barrier method of contraception.

Exclusion Criteria:

  1. DLBCL with central nervous system (CNS) involvement with active brain or leptomeningeal disease
  2. Known human immunodeficiency (HIV; testing not required) or HIV-related malignancy
  3. Known hepatitis B surface antigen positive or known or active hepatitis C infection
  4. Prior autologous stem cell transplant (ASCT) or chimeric antigen receptor T-cell (CAR-T) cell infusion within 90 days of screening
  5. Prior allogeneic stem cell transplantation
  6. Unstable/inadequate cardiac function
  7. Known gastrointestinal (GI) disease or GI procedure that interferes with swallowing/absorption of oral drug
  8. Major surgery within 14 days before the first dose of study drug
  9. Serious infection (bacterial/fungal/viral) requiring parenteral antibiotic/antiviral therapy for >5 days within 21 days prior to first dose of study drug
  10. Treatment with high-dose corticosteroids for anticancer purposes within 7 days before the first dose of mivavotinib.
  11. Use of medication known to be inhibitors or inducers of P-glycoprotein (P-gp) and/or Cytochrome P (CYP)3A
  12. Female patients who are pregnant, lactating or breastfeeding.
  13. Any radiation therapy within 3 weeks prior to first dose of study treatment.
  14. Systemic anticancer treatment within 3 weeks before first dose of study treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Continuous Dosing Schedule
Mivavotinib 100 mg once daily (QD)
Drug: Mivavotinib
oral tablet
Other Names:
  • CB-659
Experimental: Induction Dosing Schedule
Mivavotinib 120 mg QD for 14 days, then 80 mg QD starting Day 15
Drug: Mivavotinib
oral tablet
Other Names:
  • CB-659

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
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
Time Frame: Start of treatment up to 21 months
Type, incidence, severity, seriousness, and study drug-relatedness of AEs assessed by CTCAE v5.0
Start of treatment up to 21 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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.
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
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.
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
CR rate per IRC according to the 2014 IWG Lugano criteria (Cheson, 2014)
Start of treatment to 21 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Calithera Biosciences, Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 23, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 24, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 24, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 1, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 1, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 8, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 4, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 31, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CX-659-401

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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