Trial Search Results

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

The main purpose of this study is to test the safety of RO6870810 given in combination with venetoclax (with or without rituximab) at different dose levels and to find out what effects, good or bad, the study drugs have on you.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Hoffmann-La Roche

Stanford Investigator(s):

Intervention(s):

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

Phase:

Phase 1

Eligibility


Inclusion Criteria

   - 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

Exclusion Criteria

   - 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.

   18. 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.

   - Prior treatment with small molecule bromodomain and extra terminal (BET) family
   inhibitor.

   - Known to be human immunodeficiency virus (HIV) positive.

   - Presence of positive test results for hepatitis B surface antigen (HBsAg) or hepatitis
   C antibodies (HcAb) (for participants receiving regimen including rituximab)

   - Pregnant or breastfeeding female.

   - Significant allergy to a biological pharmaceutical therapy that, in the opinion of the
   Investigator, poses an increased risk to the participant.

   - 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.

   - History of severe allergic or anaphylactic reaction to humanized or murine monoclonal
   antibodies (for participants receiving regimen including rituximab).

   - Known sensitivity or allergy to murine products or any component of RO6870810,
   venetoclax, or rituximab.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Chaitasi Majmudar
650-736-0959
Recruiting