A study of Avelumab in combination with immune agonist, epigenetic modulator, CD20 antagonist and/or conventional chemotherapy in patients with large B-Cell lymphoma
- Conditions
- Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)MedDRA version: 20.0 Level: PT Classification code 10012822 Term: Diffuse large B-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002904-15-DK
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 304
1. Any of the following as defined by the WHO, 2016 lymphoid neoplasm
classification and histologically confirmed:
- Discussed large B-cell lymphoma (DLBCL), Non Otherwise Specified
(NOS)
- Germinal center B-cell type (GCB)
- Activated B-cell type (ABC)
- High-grade B-cell lymphoma (HGBCL)
- HGBCL with MYC and BCL2 and/or BCL6 rearrangements
- T-cell histocyte-rich large B-cell lymphoma
- EBV+ DLBCL, NOS
- HHV8+ DLBCL, NOS
2. Documentation that the disease is relapsed or refractory following at least 2 lines (and a maximum of 4 lines) of prior rituximab containing multi-agent chemotherapy which may include an autologous stem cell transplantation unless patients are not considered suitable for intensive second-line chemotherapy or autologous stem cell transplantation. Patients who are ineligible for intensive second line chemotherapy, must have received at least one prior rituximab-containing combination
chemotherapy regimen.
3. Patients previously treated with bendamustine must have experienced a response duration =6 months.
4. Documentation of baseline measurable disease with at least 1 bi-dimensional lesion with longest diameter (LDi) >1.5 cm on CT scan which is fluorodeoxyglucose (FDG) avid on PET scan.
5. A biopsy (archived or Screening/recent) will be collected at Screening.
6. Estimated life expectancy =3 months.
7. At least 18 years of age (or =20 years in Japan).
8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
9. All adverse events must have resolved to NCI CTCAE v.4.03 Grade =1 (with the exception of alopecia and other Grade =2 AEs not considered medically relevant in the judgment of the Investigator).
10. Patients must have an adequate bone marrow function, including: a. Absolute neutrophil count (ANC) =1.5 x 10(9)/L; b. Platelet count =100 x 10(9)/L; c. Hemoglobin =8 g/dL.
11. Patients must have adequate liver function, including: a. Total bilirubin level =1.5 × upper limit of normal (ULN); b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 x ULN.
12. Patients must have an adequate renal function as evidenced by a creatinine clearance =40 mL/min as calculated using the Cockcroft-Gault equation.
13. Serum or urine pregnancy test (for females of childbearing potential) must be negative.
14. Female patients of non-childbearing potential must meet at least 1 of the following
criteria: Achieved postmenopausal status, defined as follows: cessation of regular menses
for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state; Have undergone a documented hysterectomy and/or bilateral oophorectomy; Have medically confirmed ovarian failure. All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential.
15. Must be willing to receive prophylactic granulocyte colony
stimulating factor (G-CSF) in al
1. Active central nervous system (CNS) lymphoma.
2. Prior organ transplantation including prior allogeneic SCT.
3. Prior therapy with an anti PD-1, anti PD-L1, anti PD-L2, anti CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody (including ipilimumab, tremelimumab or any other antibody, or drug specifically targeting T-cell co-stimulatory or immune checkpoint pathways).
4. Use of any standard or experimental anti-cancer therapy within 2 weeks to first dose of study treatment, including cytoreductive therapy and radiotherapy, immunotherapy, or cytokine therapy (except for erythropoietin).
5. Use of any non-drug anti-cancer therapy including chimeric antigen receptor (CAR) T-Cell (CAR-T-Cell) therapy.
6. Major surgery within 28 days prior to first dose of study treatment.
7. Diagnosis of any other malignancy =3 years prior to first dose of study treatment, with the exception of: (i) adequately treated basal cell or squamous cell skin cancer, (ii) carcinoma in situ of the breast or cervix, or (iii) low-grade (Gleason =6) prostate cancer on surveillance without any plans for treatment intervention (eg, surgery, radiation, or castration).
8. Known history of testing positive for human immunodeficiency virus ( HIV) or known acquired immunodeficiency syndrome.
9. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen, positive HBV core antibody or HCV ribonucleic acid (RNA) if anti-HCV antibody screening test positive).
10. Active infection requiring systemic therapy.
11. Vaccination within 4 weeks prior to randomization and while on trial is prohibited except for administration of inactivated vaccines.
12. Peripheral neuropathy with functional impairment (for the Phase 3 component only due to oxaliplatin).
13. Current use of immunosuppressive medication, EXCEPT for the following: a.) intranasal, inhaled, eye drops, topical steroids, or local steroid injection (eg, intra-articular injection); b.) Systemic corticosteroids at physiologic doses =10 mg/day of prednisone or equivalent; c.) Steroids as premedication for hypersensitivity reactions
(eg, CT scan premedication).
14. Active autoimmune disease that might deteriorate when receiving an
immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypoor
hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
15. Known anaphylaxis or severe hypersensitivity to rituximab or other monoclonal
antibodies, mannitol, or any of the compounds used in this study or to compounds
with a similar chemical or biological composition.72
16. Clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke/transient ischemic attack [TIA]/symptomatic pulmonary embolism (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (=New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication, other severe acute or chronic medical (including colitis, inflammatory bowel disease, pneumonitis, uncontrolled asthma
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method