A Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of the Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Participants With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Description

The purpose of this study is to evaluate the safety, tolerability and clinical activity of RO6870810 in combination with venetoclax and when co-administered with rituximab in participants with relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Study Start Date

August, 28 2017

Estimated Completion Date

July 2020

Interventions

  • Drug: RO6870810
  • Drug: Venetoclax
  • Drug: Rituximab

Study ID

Hoffmann-La Roche -- NP39461

Status

Recruiting

Trial ID

NCT03255096

Study Type

Interventional

Trial Phase

Phase 1

Enrollment Quota

94

Sponsor

Hoffmann-La Roche

Inclusion Criteria 1. Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2. 2. Life expectancy >3 months as per investigator's assessment. 3. Participantts with diffuse large B-cell lymphoma (DLBCL) relapsed or refractory to ? 1 course of chemotherapy including an anti-CD20 monoclonal antibody, and not eligible for autologous stem cell transplantation (ASCT) (including due to chemorefractory disease). Participants with transformed FL are eligible, provided DLBCL histology is biopsy-confirmed prior to study entry and a treatment regimen as described above has been administered. The Sponsor retains the option to limit the number of participants enrolled with transformed FL. 4. Acceptable liver function, as specified below:
  • Total bilirubin ? 2 times upper limit of normal (ULN). (Participants with known Gilbert's disease who has serum bilirubin ? 3 × ULN may be enrolled).
  • Aspartate transaminase (AST
  • SGOT), alanine transaminase (ALT SGPT) ? 2.5 × ULN, (or ? 5 × ULN if tumor involvement (liver) is present).
  • Gamma-glutamyl transferase (GGT) alkaline phosphatase ? 2.5 × ULN. 5. Acceptable renal function, as specified below:: • Creatinine clearance (CrCl) calculated by Cockroft-Gault formula of ? 60 mL/min. 6. Acceptable hematologic status (growth factors cannot be used within the previous 7 days), as specified below:
  • Absolute neutrophil count (ANC) ? 1000 cells/?L
  • Hemoglobin ? 9 g/dL
  • Platelet count ? 75,000 (platelets/?L) 7. Serum calcium (corrected for albumin) level at or below the ULN (treatment of hypercalcemia is allowed and participant may enroll if hypercalcemia returns to normal with standard treatment). 8. Acceptable coagulation status, as specified below:
  • Prothrombin time (PT)/partial thromboplastin time (PTT) ? 1.2 × ULN (unless receiving anticoagulation therapy, if receiving anticoagulation therapy, eligibility will be based upon international normalized ratio [INR]).
  • INR ? 1.6 (unless receiving anticoagulation therapy).
  • If receiving warfarin: INR ? 3.0 and no active bleeding (i.e., no bleeding within 14 days prior to first dose of study therapy). 9. Acceptable method of contraception Exclusion Criteria 1. Current central nervous system (CNS) lymphoma or leptomeningeal infiltration. 2. New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial infarction, within the past 6 months, unstable arrhythmia, or known pericardial disease. 3. Fredericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or history of congenital long QT syndrome. 4. Any electrocardiogram (ECG) abnormality, which in the opinion of the Investigator would preclude safe participation in the study. 5. Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy. 6. Known clinically important respiratory impairment 7. Grade ? 3 sensory or motor neuropathy. 8. Any Grade >1 (according to the NCI CTCAE 4.03) adverse reaction unresolved from previous treatments and not readily managed and controlled with supportive care. 9. Serious non-malignant disease that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor. 10. History of progressive multifocal leukoencephalopathy (PML). 11. History of other malignancy within 2 years prior to screening, except for ductal carcinoma in situ not requiring chemotherapy, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, low-grade, localized prostate cancer (Gleason score ? 7) not requiring treatment or appropriately treated Stage I uterine cancer. 12. Completion of ASCT within 100 days prior to Day 1 of Cycle1. 13. Prior standard or investigational anti-cancer therapy, as specified below:
  • Radio-immunoconjugate within 12 weeks prior to Day 1 of Cycle 1.
  • Monoclonal antibody or antibody-drug conjugate (ADC) therapy within 3 weeks prior to Day 1 of Cycle 1.
  • Radiotherapy, chemotherapy, or targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1. 14. History of major solid organ transplant (i.e., heart, lungs, liver and kidney). 15. History of an allogeneic bone marrow transplant. 16. Major surgical procedure within 28 days prior to Day 1 of Cycle 1. 17. Treatment with systemic corticosteroids ? 20 mg/day prednisone or equivalent, for non-lymphoma treatment reasons. For lower acceptable doses, documentation of a stable dose for at least 4 weeks prior to Day 1 of Cycle 1 is required. 18. Treatment with strong to moderate CYP3A inhibitors or moderate CYP3A inducers within 7 days prior to the first dose of study treatment. 19. Treatment with strong CYP3A inducers within 14 days prior to the first dose of study treatment of RO6870810/venetoclax. 20. Consumption of grapefruits, grapefruit products, Seville oranges (including marmalade that contains Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax. 21. Participants who are currently receiving any other investigational agent or have received an investigational agent within 30 days or 5 half-lives prior to study entry, whichever is longer. 22. Prior treatment with small molecule bromodomain and extra terminal (BET) family inhibitor. 23. Known to be human immunodeficiency virus (HIV) positive. 24. Presence of positive test results for hepatitis B surface antigen (HBsAg) or hepatitis C antibodies (HcAb) (for participants receiving regimen including rituximab) 25. Pregnant or breastfeeding female. 26. Significant allergy to a biological pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the participant. 27. Uncontrolled cancer pain. Participants requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to enrollment. 28. History of severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies (for participants receiving regimen including rituximab). 29. Known sensitivity or allergy to murine products or any component of RO6870810, venetoclax, or rituximab.
  • Gender

    All

    Ages

    18 Years and older

    Accepts Healthy Volunteers

    No

    Study Locations and Contact Information (24)

    Study Location Distance Name Phone Email
    Dana Farber Cancer Inst Dept of Medical Oncology - Boston, Massachusetts 2.6 miles None None None
    Dana Farber Cancer Inst Dept of Medical Oncology - Boston, Massachusetts 2.6 miles None None None
    Dana Farber Cancer Inst Dept of Medical Oncology - Boston, Massachusetts 2.6 miles None None None
    Dana Farber Cancer Inst Dept of Medical Oncology - Boston, Massachusetts 2.6 miles None None None
    Dana Farber Cancer Inst Dept of Medical Oncology - Boston, Massachusetts 2.6 miles None None None
    Columbia University Medical Center Center for Lymphoid Malignancies - New York, New York 186.0 miles None None None
    Columbia University Medical Center Center for Lymphoid Malignancies - New York, New York 186.0 miles None None None
    Columbia University Medical Center Center for Lymphoid Malignancies - New York, New York 186.0 miles None None None
    Columbia University Medical Center Center for Lymphoid Malignancies - New York, New York 186.0 miles None None None
    Columbia University Medical Center Center for Lymphoid Malignancies - New York, New York 186.0 miles None None None
    Weill Cornell Medical College - New York, New York 187.1 miles None None None
    Weill Cornell Medical College - New York, New York 187.1 miles None None None
    Weill Cornell Medical College - New York, New York 187.1 miles None None None
    Levine Cancer Institute Blythe - Charlotte, North Carolina 722.4 miles None None None
    Levine Cancer Institute Blythe - Charlotte, North Carolina 722.4 miles None None None
    Levine Cancer Institute Blythe - Charlotte, North Carolina 722.4 miles None None None
    Levine Cancer Institute Blythe - Charlotte, North Carolina 722.4 miles None None None
    Levine Cancer Institute Blythe - Charlotte, North Carolina 722.4 miles None None None
    MD Anderson Cancer Center Department of Lymphoma Myeloma - Houston, Texas 1,609.9 miles None None None
    MD Anderson Cancer Center Department of Lymphoma Myeloma - Houston, Texas 1,609.9 miles None None None
    MD Anderson Cancer Center Department of Lymphoma Myeloma - Houston, Texas 1,609.9 miles None None None
    MD Anderson Cancer Center Department of Lymphoma Myeloma - Houston, Texas 1,609.9 miles None None None
    MD Anderson Cancer Center Department of Lymphoma Myeloma - Houston, Texas 1,609.9 miles None None None
    City of Hope National Medical Center - Duarte, California 2,578.2 miles None None None

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