A Study to Evaluate Safety, Pharmacokinetics, and Clinical Activity of Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Participants With Relapsed/Refractory DLBCL and/or High-Grade B-Cell Lymphoma and/or High Grade B-Cell Lymphoma With MYC and/or BCL2 and/or BCL6

Completed · Phase 1

Conditions studied: Diffuse Large B-cell Lymphoma, High-Grade B-cell Lymphoma

In brief

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) and/or high-grade B-cell lymphoma with myelocytomatosis oncogene (MYC) and/or B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) gene rearrangements (HGBL-DH/TH).

Key facts

Study ID

NCT03255096

Run by

Hoffmann-La Roche

People needed

39

Starts

2017-08-28

Expected to finish

2019-07-03

Last updated by the study team

2022-01-24

Who can join

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

You may qualify if…

• Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
• Life expectancy >3 months as per investigator's assessment.
• Part 1 and Part 2 Group 1: 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 or HGBL-DH/TH 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.
• Part 2, Group 2: Patients identified with DE-DLBCL (expression MYC ≥40%, BCL2 > 50%) and or HGBL-DH/TH, relapsed or refractory to >= 1 course of chemotherapy including an anti-CD20 monoclonal antibody, and not eligible for ASCT (including due to chemorefractory disease). Patients with transformed follicular lymphoma (FL) are eligible, provided DE-DLBCL and/or HGBL-DH/TH 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.
• Part 1 and Part 2: Willing to provide the protocol specified tumor biopsy(ies): at screening a fresh biopsy (if no archival biopsy tissue of less than 3 months prior to treatment and without intercurrent treatment is available); Part 2: Willing to provide an additional biopsy on Cycle 2 Day 15 (+ 2 days).
• 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.
• Acceptable renal function, as specified below:
• Creatinine clearance (CrCl) calculated by Cockroft-Gault formula of ≥ 60 mL/min.
• Acceptable hematologic status (growth factors cannot be used within the previous 7 days), as specified below:
• Absolute neutrophil count (ANC) ≥ 1000 cells/μL
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 75,000 (platelets/μL)
• Uncontrolled symptomatic hypercalcemia.
• Acceptable coagulation status, as specified below:
• Prothrombin time (PT) and 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).
• Acceptable method of contraception

You may not qualify if…

• Current central nervous system (CNS) lymphoma or leptomeningeal infiltration.
• New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial infarction, within the past 6 months, unstable arrhythmia, or known pericardial disease.
• Fredericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or history of congenital long QT syndrome.
• Any electrocardiogram (ECG) abnormality, which in the opinion of the Investigator would preclude safe participation in the study.
• Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy.
• Clinically important respiratory impairment
• Grade ≥ 3 sensory or motor neuropathy.
• 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.
• Serious non-malignant disease that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
• History of progressive multifocal leukoencephalopathy (PML).
• 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.
• Completion of ASCT within 100 days prior to Day 1 of Cycle1.
• Prior standard or investigational anti-cancer therapy, as specified below:
• Radio-immunoconjugate 4 weeks or 5 half-lives, whichever is longer 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.
• CAR T-cell therapy 30 days prior to Day 1 of Cycle 1.
• History of major solid organ transplant (i.e., heart, lungs, liver and kidney).
• History of an allogeneic bone marrow transplant.
• Major surgical procedure within 28 days prior to Day 1 of Cycle 1.
• 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.
• Treatment with strong to moderate CYP3A inhibitors or moderate CYP3A inducers within 7 days prior to the first dose of study treatment.
• Treatment with strong CYP3A inducers within 14 days prior to the first dose of study treatment of RO6870810/venetoclax.
• 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.
• Participants who are currently receiving any other investigational agent ((other than anti-cancer therapy as specified in exclusion criteria number 13) or have received an investigational agent within 30 days or 5 half-lives prior to Day 1 of Cycle 1, whichever is longer.

Where it is running

• City of Hope National Medical Center — Duarte, California, United States
• Stanford Cancer Center — Stanford, California, United States
• Weill Cornell Medical College — New York, New York, United States
• Levine Cancer Institute - Blythe — Charlotte, North Carolina, United States
• Peter MacCallum Cancer Centre-East Melbourne — Melbourne, Victoria, Australia
• Rigshospitalet; Hæmatologisk Klinik — København Ø, Denmark
• Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia — Barcelona, Spain
• Hospital Duran i Reynals; Servicio de Hematologia — Barcelona, Spain
• START Madrid-FJD, Hospital Fundacion Jimenez Diaz — Madrid, Spain

Full record on ClinicalTrials.gov

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