Study to Assess Enzastaurin + R-CHOP in Subjects With DLBCL With the Genomic Biomarker DGM1™

Completed · Phase 3 · Has a placebo group

Conditions studied: Diffuse Large B-Cell Lymphoma

In brief

This randomized, placebo-controlled phase 3 study planned to enroll approximately 235 treatment-naïve subjects with high-risk Diffuse Large B-Cell Lymphoma (DLBCL). Subjects were randomized 1:1 to R-CHOP plus enzastaurin or R-CHOP (plus placebo during induction). All subjects received up to 6 cycles (3 weeks per cycle) of treatment. PET/ CT was used to assess radiographic response at the end of treatment. Each subject's treatment assignment was unblinded after combination phase tumor response assessment. Subjects randomized to the enzastaurin arm who have a complete response (CR) or partial response (PR) (at investigator's discretion) by Lugano Classification had the opportunity to continue in the single-agent phase of the study and receive single-agent enzastaurin for up to 2 additional years.

Key facts

Study ID

NCT03263026

Run by

Denovo Biopharma LLC

People needed

256

Starts

2018-03-20

Expected to finish

2022-08-11

Last updated by the study team

2025-01-23

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male or female at least 18 years of age and able to provide informed consent.
• Histologically confirmed diagnosis of CD20-positive DLBCL based on the WHO classification (2016); the diagnosis must be confirmed at the enrolling site. Subjects with high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements and high-grade B-cell lymphoma, NOS are eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• International Prognostic Index (IPI) score of at least 3.
• Estimated life expectancy of at least 12 weeks.
• Adequate organ function as follows (within 14 days prior to randomization):
• Hepatic: total bilirubin ≤ 1.5 times upper limit of normal (ULN) (≤ 5 times ULN in the case of Gilberts Syndrome, liver or pancreatic involvement by lymphoma); alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 times ULN (≤ 5 times ULN if liver involvement)
• Renal: creatinine clearance of ≥ 40 mL/min by Cockcroft- Gault equation
• Bone marrow: platelets ≥75 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, hemoglobin ≥8 g/dL. (Platelets ≥50 x 109/L, ANC ≥ 1.0 x 109/L, hemoglobin ≥ 7 g/dL permitted if documented bone marrow involvement)
• Male or female with reproductive potential, must be willing to use an approved contraceptive method (for example, intrauterine device (IUD), birth control pills, or barrier device) during and for 3 months after discontinuation of study treatment. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization.
• Men are considered of reproductive potential unless they have undergone a vasectomy and confirmed sterile by a post-vasectomy semen analysis.
• Women are considered of reproductive potential unless they have undergone hysterectomy and/or surgical sterilization (at least 6 weeks following a bilateral oophorectomy, bilateral tubal ligation, or bilateral tubal occlusive procedure that has been confirmed in accordance with the device's label) or achieved postmenopausal status (defined as cessation of regular menses for greater than 12 consecutive months in women at least 45 years of age).
• Left ventricular ejection fraction ≥50% by echocardiography or nuclear medicine multi-gated scan.
• Must be able to swallow tablets.
• Must be able to comply with study protocol procedures.
• Willing to consent to have blood stored for possible future biomarker and disease analysis.
• Must have available and willing to submit pre-systemic treatment DLBCL tumor biopsy tissue/slides for central pathology review.

You may not qualify if…

• Received treatment with an investigational drug within the last 30 days.
• Receiving or has received radiation or any other systemic anticancer treatment for lymphoma (Up to 7 days of corticosteroids are permitted but must be administered after eligibility IPI determination and imaging scans).
• History of indolent lymphoma or follicular Grade 3b lymphoma.
• Primary mediastinal (thymic) large B-cell lymphoma.
• B-cell lymphoma, unclassifiable, with features. intermediate between DLBCL and classical Hodgkin lymphoma.
• Burkitt lymphoma.
• Pregnancy or breastfeeding.
• Known central nervous system (CNS) involvement.
• Any significant concomitant disorder based on the discretion of the investigator, including but not limited to active bacterial, fungal, or viral infection, incompatible with participation in the study.
• A second primary malignancy (except adequately treated non-melanoma skin cancer); subjects who have had another malignancy in the past, but have been disease-free for more than 5 years, and subjects who have had a localized malignancy treated with curative intent and disease free for more than 2 years are eligible.
• Use of a strong inducer or moderate or strong inhibitor of CYP3A4 within 7 days prior to start of study therapy or expected requirement for use on study therapy.
• Personal or immediate family history of long QT syndrome, QTc interval >450 msec (males) or >470 msec (females) at screening (recommended that QTc be calculated using Fridericia correction formula, QTcF: see Section 6.2.1), or a history of unexplained syncope.
• Use of any medication that can prolong the QT/QTc interval within 7 days prior to start of study therapy or expected requirement for use on study therapy.
• History of severe allergic or anaphylactic reaction to monoclonal antibody therapy.
• Confirmed diagnosis of progressive multifocal leukoencephalopathy.
• Ongoing grade 2 or higher peripheral neuropathy.
• Have any of the following cardiac disorders: uncontrolled hypertension, unstable angina, myocardial infarction within 8 weeks of randomization, New York Heart Association (NYHA) Grade 2 or higher congestive heart failure, ventricular arrhythmia requiring medication within 1 year of randomization, Fontaine Classification stage III or higher peripheral arterial disease.
• Received a live vaccine within 28 days of study Day 1.
• HIV positive.
• Evidence of chronic hepatitis C infection as indicated by antibody to HCV with positive HCV-RNA.
• Evidence of chronic hepatitis B infection as indicated by either:
• HBsAg+ or
• HBcAb+ with HBV-DNA+ (any detectable amount is considered positive)

Where it is running

• Oncology Specialties: Clearview Cancer Institute — Huntsville, Alabama, United States
• University of Arizona — Tucson, Arizona, United States
• Central Arkansas Radiation Therapy Institute — Little Rock, Arkansas, United States
• Desert Hematology — Rancho Mirage, California, United States
• Loyola University Medical Center — Maywood, Illinois, United States
• Illinois CancerCare — Peoria, Illinois, United States
• Indiana University — Indianapolis, Indiana, United States
• Norton Cancer Institute Oncology Practices - St. Matthews Location — Louisville, Kentucky, United States
• Mayo Clinic, Rochester — Rochester, Minnesota, United States
• Mercy Research — Springfield, Missouri, United States
• Saint Louis University — St Louis, Missouri, United States
• Comprehensive Cancer Centers of Nevada — Las Vegas, Nevada, United States
• Norris Cotton Cancer Center Dartmouth-Hitchcock Medical Center — Lebanon, New Hampshire, United States
• Summit Medical Group — Morristown, New Jersey, United States
• Atlantic Health System/ Morristown Meeical Center — Morristown, New Jersey, United States
• New York Medical College — Hawthorne, New York, United States
• Icahn School of Medicine at Mount Sinai — New York, New York, United States
• Stony Brook Cancer Center — Stony Brook, New York, United States
• Hematology & Oncology Associates, Inc. — Canton, Ohio, United States
• Tri-County Hematology & Oncology Associates, Inc. — Massillon, Ohio, United States
• Toledo Clinic Cancer Centers — Toledo, Ohio, United States
• University of Texas Southwestern Medical Center - Harold C. Simmons Comprehensive Cancer Center — Dallas, Texas, United States
• Oncology Consultants: Memorial City — Houston, Texas, United States
• Swedish Cancer Institute — Seattle, Washington, United States
• Seattle Cancer Center Alliance — Seattle, Washington, United States

Full record on ClinicalTrials.gov

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