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

This study is not yet open for participant recruitment.
Verified August 2017 by Denovo Biopharma LLC
Sponsor:
ClinicalTrials.gov Identifier:
NCT03263026
First Posted: August 28, 2017
Last Update Posted: September 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Denovo Biopharma LLC
  Purpose
This randomized, placebo-controlled phase 3 study is planned to enroll approximately 235 treatment-naïve subjects with high-risk Diffuse Large B-Cell Lymphoma (DLBCL). Subjects will be randomized 1:1 to R-CHOP plus enzastaurin or R CHOP (plus placebo during induction). All subjects will receive up to 6 cycles (3 weeks per cycle) of treatment. PET/ CT will be used to assess radiographic response at the end of treatment. Each subject's treatment assignment will be unblinded after initial phase of treatment. Subjects randomized to the enzastaurin arm who have a response will be offered maintenance treatment of the study drug for up to 2 additional years.

Condition Intervention Phase
Diffuse Large B-Cell Lymphoma Drug: Enzastaurin Hydrochloride Other: R-CHOP + placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Subjects will be randomly assigned to receive one of the following: R-CHOP plus enzastaurin or R-CHOP plus placebo, during two treatment periods: induction and maintenance. Induction phase: all subjects will receive R-CHOP for up to six, 21-day cycles. Subjects in the enzastaurin arm will receive a 1125 mg loading dose on Day 2 followed by 500 mg daily. Subjects in the placebo arm will take an identical number of tablets.

After 4-<6 cycles of induction therapy treatment assignment will be unblinded. Subjects in the enzastaurin arm who have achieved a response will have the opportunity to continue in the single-agent, maintenance phase of the study, and will receive single-agent enzastaurin at 500 mg/day for up to 2 years. Eligible subjects must begin the maintenance phase of the study within 6 weeks of completing induction therapy.

Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Denovo Biopharma, the study Sponsor, will also be blinded.
Primary Purpose: Treatment
Official Title: A Randomized Phase 3 Study to Evaluate the Efficacy and Safety of Enzastaurin Plus R-CHOP Versus R-CHOP in Treatment-Naive Subjects With High-Risk Diffuse Large B-Cell Lymphoma Who Possess the Novel Genomic Biomarker DGM1™

Resource links provided by NLM:


Further study details as provided by Denovo Biopharma LLC:

Primary Outcome Measures:
  • Overall survival in subjects who possess the DGM1™ biomarker [ Time Frame: 3.5 years ]
    The primary objective of this study is to compare the effect of R-CHOP/enzastaurin versus R-CHOP alone on overall survival in treatment naive, high-risk subjects with DLBCL who possess the DGM1™ biomarker.


Secondary Outcome Measures:
  • Overall survival in subjects who do not possess the DGM1™ biomarker [ Time Frame: 3.5 years ]
    A secondary objective of this study is to compare the effect of R-CHOP/enzastaurin versus R-CHOP alone on overall survival in treatment naive, high-risk subjects with DLBCL who do not possess the DGM1™ biomarker.

  • Safety of enzastaurin by assessing incidence of adverse events/serious adverse events, change of vital signs, ECG results, lab results, and physical exam findings from baseline [ Time Frame: 3.5 years ]

    The safety analysis will include the following:

    • Summary of extent of exposure
    • Summary of the number of blood transfusions required
    • Summary of adverse events, serious adverse events, and subjects discontinuing for adverse events rates
    • Summary of laboratory findings and change from baseline
    • Summary of QTc data and change from baseline according to ICH E14
    • Summary of other relevant safety observations
    • Listings of laboratory and non-laboratory adverse events by maximum CTCAE grade and relationship to study drug using CTCAE v4.03


Other Outcome Measures:
  • Presence of chromaturia as a predictor of efficacy [ Time Frame: 3.5 years ]
    Urine color will be analyzed by the central lab and overall survival will be determined for subjects with reddish discoloration of the urine. Testing may be performed to define the chemical profile of the urine.


Estimated Enrollment: 235
Anticipated Study Start Date: October 2017
Estimated Study Completion Date: May 2021
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: R-CHOP + enzastaurin hydrochloride
Subjects in the R-CHOP + enzastaurin Arm will receive R-CHOP (Rituximab-375 mg/m2 i.v., Cyclophosphamide-750 mg/m2 i.v., Doxorubicin-50 mg/m2 i.v., Vincristine-1.4 mg/m2 i.v. (2 mg max), and Prednisone-100 mg p.o.), as directed, plus a 1125 mg loading dose of enzastaurin on Day 2 followed by 500 mg daily.
Drug: Enzastaurin Hydrochloride
R-CHOP + Enzastaurin (Kinenza®) 125 mg
Other Name: Kinenza®
Placebo Comparator: R-CHOP + placebo
Subjects in the R-CHOP + placebo Arm will receive R-CHOP (Rituximab-375 mg/m2 i.v., Cyclophosphamide-750 mg/m2 i.v., Doxorubicin-50 mg/m2 i.v., Vincristine-1.4 mg/m2 i.v. (2 mg max), and Prednisone-100 mg p.o.), as directed, plus an identical number of tablets as the subjects in the enzastaurin Arm.
Other: R-CHOP + placebo
R-CHOP + placebo
Other Name: Placebo

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (All questions must be answered "YES" in order for the subject to be considered for the study):

  1. Is the subject a male or female between18 and 75 years of age inclusive who is able to provide informed consent?
  2. Does the subject have histologically-confirmed diagnosis of CD20-positive DLBCL based on the WHO classification? The diagnosis must be confirmed at the enrolling site. Subjects with history of indolent lymphoma or follicular Grade 3 lymphoma are not eligible.
  3. Does the subject have an ECOG score of 0, 1 or 2?
  4. Does the subject have an IPI score of at least 3?
  5. Does the subject have an estimated life expectancy of at least 12 weeks?
  6. Does the subject have adequate organ function as follows:

    1. Hepatic: total bilirubin ≤1.5 times upper limit of normal (ULN); alanine transaminase (ALT) and aspartate transaminase (AST) ≤1.5 times ULN (<5 times ULN if liver involvement)
    2. Renal: estimated GFR of >50 ml/min by Cockcroft- Gault equation
    3. Bone marrow: platelets ≥75 x 109/L, absolute neutrophil count (ANC) ≥1.5 x 109/L, hemoglobin ≥10 g/dL, unless there is bone marrow involvement
  7. If the subject is a male or female with reproductive potential, is he/she 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 start of treatment.
  8. Does the subject have a left ventricular ejection fraction ≥50% by echocardiography or nuclear medicine multi-gated scan?
  9. Is the subject able to swallow tablets?
  10. Does the subject have adequate transportation to allow for required follow-up visits?
  11. Does the subject agree to have blood stored for possible future biomarker analysis?

Exclusion Criteria (All must be answered "NO" in order for the subject to be considered for the study):

  1. Has the subject received treatment with an investigational drug within the last 30 days?
  2. Is the subject receiving, or has the subject received, any other radiation or systemic anticancer treatment for lymphoma?
  3. Is the subject pregnant or breastfeeding?
  4. Does the subject have known central nervous system (CNS) involvement?
  5. Does the subject have any significant concomitant disorder, including active bacterial, fungal, or viral infection, incompatible with participation in the study?
  6. Does the subject have a second primary malignancy (except adequately treated non-melanoma skin cancer)? Patients who have had another malignancy in the past, but have been disease-free for more than 5 years, are eligible.
  7. Is the subject unable to discontinue use of a concomitant medication that is a strong inducer or inhibitor of CYP3A4? (See Appendix A).
  8. Does the subject have a family history of long QT syndrome, or a QTc interval >450 (males) or 470 (females) at screening, a history of arrhythmias or a history of unexplained syncope?
  9. Must the subject take any medication that can prolong the QT/QTc interval? (See Appendix C)
  10. Does the subject have a history of severe allergic or anaphylactic reaction to monoclonal antibody therapy?
  11. Does the subject have a confirmed diagnosis of progressive multifocal leukoencephalopathy?
  12. Does the subject have a history of grade 2 or higher peripheral neuropathy?
  13. Does the subject have any of the following cardiac disorders: uncontrolled hypertension, unstable angina, myocardial infarction within 8 weeks of Day1, NYHA Grade 2 or higher congestive heart failure, ventricular arrhythmia requiring medication within 1 year of Day 1, NYHA Grade 2 or higher peripheral vascular disease?
  14. Has the subject received a live vaccine within 28 days of study Day 1?
  15. Is the subject HIV positive?
  16. Does the subject have evidence of chronic hepatitis C infection as indicated by antibody to HCV with positive HCV-RNA?
  17. Does the subject have evidence of chronic hepatitis B infection as indicated by either:

    1. HBsAg+ or
    2. HBcAb+ with HBV-DNA+
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03263026


Contacts
Contact: Glenn Brown (800) 279-8082 ext 512-295-1221 Glenn.Brown@chiltern.com
Contact: Curtis Reinard (800) 279-8082 ext 484-679-2546 Curtis.Reinard@chiltern.com

Locations
United States, Washington
Virginia Mason Medical Center Not yet recruiting
Seattle, Washington, United States, 98101
Sponsors and Collaborators
Denovo Biopharma LLC
Investigators
Study Director: Wen Luo, Ph.D. Denovo BioPharma
  More Information

Responsible Party: Denovo Biopharma LLC
ClinicalTrials.gov Identifier: NCT03263026     History of Changes
Other Study ID Numbers: DB102-02
First Submitted: August 18, 2017
First Posted: August 28, 2017
Last Update Posted: September 1, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Denovo Biopharma LLC:
Lymphoma
Non-Hodgkin's Lymphoma
enzastaurin

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Prednisone
Vincristine
Doxorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic