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Active Clinical Trials

BO29563

Active NCT:
02596971
West Penn Hospital
West Penn Hospital

Category:
Bone and Muscle
Sponsor: 
F. Hoffmann-La Roche Ltd
Contact: 

For more information, please contact Rich Wonder at 412-578-4492 or Rich.Wonder@ahn.org

BO29563: A PHASE IB/II STUDY EVALUATING THE SAFETY AND EFFICACY OF ATEZOLIZUMAB IN COMBINATION WITH EITHER OBINUTUZUMAB PLUS BENDAMUSTINE OR OBINUTUZUMAB PLUS CHOP IN PATIENTS WITH FOLLICULAR LYMPHOMA OR RITUXIMAB PLUS CHOP IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA

Purpose: 

This study will evaluate the safety, efficacy, and pharmacokinetics of induction treatment consisting of atezolizumab in combination with obinutuzumab plus bendamustine (Atezo-G-benda) in patients with FL, atezolizumab in combination with obinutuzumab plus CHOP (Atezo-G-CHOP) in patients with FL, and atezolizumab in combination with rituximab plus CHOP (Atezo-R-CHOP) in patients with DLBCL, followed by post-induction treatment consisting of either atezolizumab plus obinutuzumab (Atezo-G) in patients with FL who achieve a CR or PR at EOI or atezolizumab alone in patients with DLBCL who achieve a CR at EOI

Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
  • For patients enrolled in the safety run-in phase: lymphoma classified as either of the following: Relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen; Previously untreated Grade 1, 2, or 3a FL that requires treatment, defined as meeting at least one of the Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria, as listed here: Bulky disease, defined as a nodal or extranodal (except spleen) mass ≥ 7 cm in the greatest diameter; Local symptoms or compromise of normal organ function due to progressive nodal disease or extranodal tumor mass Presence of B symptoms; Presence of symptomatic extranodal disease (e.g., pleural effusions, peritoneal ascites); Cytopenias due to underlying lymphoma (i.e., ANC < 1.0 ×109/L, hemoglobin < 10 g/dL, and/or platelet count < 100×109/L); Involvement of ≥ 3 nodal sites, each with a diameter of ≥ 3 cm
  • For patients enrolled in the expansion phase: lymphoma classified as either of the following: Previously untreated Grade 1, 2, or 3a FL that requires treatment, defined as meeting at least one of the GELF criteria (listed above); Previously untreated advanced DLBCL, defined as Stage III or IV with an International Prognostic Index (IPI) ≥ 2 or Stage II with bulky disease (defined as at least one lesion ≥ 7 cm)
  • Histologically documented CD20-positive lymphoma
  • Fluorodeoxyglucose-avid lymphoma (i.e., PET-positive lymphoma)
  • At least one bi-dimensionally measurable lesion (> 1.5 centimeters in its largest dimension by computed tomography scan or magnetic resonance imaging)
  • Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL or DLBCL; For patients with FL, if the available biopsy was not done within 12 months, a repeat biopsy is strongly recommended.
  • For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 18 months after the last dose of study treatment for patients in the Atezo-G-benda and Atezo-G-CHOP treatment groups or for at least 12 months after the last dose of study treatment for patients in the Atezo-R-CHOP treatment group; Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper IUDs. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.-
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined below: With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 3 months after the last dose of study treatment. Men must refrain from donating sperm for the same period.; With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 3 months after the last dose of study treatment.; The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

  • Histological evidence of transformation of FL into high-grade B-cell non-Hodgkin's lymphoma (NHL)
  • Central nervous system lymphoma or leptomeningeal infiltration
  • For participants with DLBCL: preplanned consolidative radiotherapy
  • Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1: Treatment with inhaled corticosteroids and mineralocorticoids is permitted; If corticosteroid treatment is urgently required for lymphoma symptom control prior to the start of study treatment, 100 mg of prednisone or equivalent can be given for a maximum of 5 days, but all tumor assessments must be completed prior to initiation of corticosteroid treatment.
  • For participants with relapsed or refractory FL (enrolled in the safety run-in phase): Prior allogeneic or autologous stem cell transplantation; Prior anthracycline therapy (in patients enrolled in the Atezo-G-CHOP treatment; group); Treatment with fludarabine or alemtuzumab within 12 months prior to Day 1 of Cycle1; Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4, anti?programmed death?1, and anti? programmed death?ligand 1 therapeutic antibodies; Treatment with a monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate within 4 weeks prior to Day 1 of Cycle 1; Radiotherapy, chemotherapy, hormonal therapy, or targeted small-molecule therapy within 2 weeks prior to Day 1 of Cycle 1; Clinically significant toxicity (other than alopecia) from prior treatment that has not resolved to Grade ≤ 2 (per National Cancer Institute Common Terminology Criteria in Adverse Events v4.0) prior to Day 1 of Cycle 1
  • History of solid organ transplantation
  • History of severe allergic or anaphylactic reaction or known sensitivity to humanized or murine monoclonal antibodies
  • Known sensitivity or allergy to murine products
  • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the MPDL3280A, obinutuzumab, rituximab, or bendamustine formulation, including mannitol
  • Known history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or evidence of active pneumonitis on screening chest CT scan; History of radiation pneumonitis in the radiation field (fibrosis) is allowed
  • Active bacterial, viral, fungal, or other infection or any major episode of infection requiring treatment with intravenous (IV) antibiotics within 4 weeks of Day 1 of Cycle 1; Caution should be exercised when considering the use of obinutuzumab and rituximab in patients with a history of recurring or chronic infections.
  • Positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening
  • Known history of HIV positive status; For patients with unknown HIV status, HIV testing will be performed at screening if required by local regulations.
  • History of progressive multifocal leukoencephalopathy
  • Vaccination with a live virus vaccine within 28 days prior to Day 1 of Cycle 1
  • History of other malignancy that could affect compliance with the protocol or interpretation of results, with the exception of the following: Curatively treated carcinoma in situ of the cervix, good-prognosis ductal carcinoma in situ of the breast, basal- or squamous-cell skin cancer, Stage I melanoma, or low-grade, early-stage localized prostate cancer; Any previously treated malignancy that has been in remission without treatment for ≥ 2 years prior to enrollment;
  • History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegenerfs granulomatosis, Sjogrenfs syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis; Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study; Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study
  • Evidence of any significant, uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm).
  • Major surgical procedure other than for diagnosis within 28 days prior to Day 1 of Cycle 1 Day 1, or anticipation of a major surgical procedure during the course of the study.
  • For patients who will be receiving CHOP: left ventricular ejection fraction < 50% by multiple-gated acquisition scan or echocardiogram
  • Inadequate hematologic function (unless due to underlying lymphoma), defined as follows: Hemoglobin < 9; g/dL; ANC < 1.5 × 109/L; Platelet count < 75 × 109;/L
  • Any of the following abnormal laboratory values (unless due to underlying lymphoma): Creatinine > 1.5 times the upper limit of normal (ULN) (unless creatinine clearance is normal) or calculated creatinine clearance < 40 mL/min (using the Cockcroft-Gault formula); AST or ALT > 2.5 ×ULN; Serum total bilirubin > 1.5 ×ULN (or > 3 ×ULN for patients with Gilbert syndrome); INR or PT > 1.5 × ULN in the absence of therapeutic anticoagulation; PTT or a PTT > 1.5 ×ULN in the absence of a lupus anticoagulant
  • Pregnant or lactating, or intending to become pregnant during the study; Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 7 days prior to Day 1 of Cycle 1.
  • Unable to comply with the study protocol, in the investigator’s judgment