| Eligibility |
1. Inclusion Criteria
- Male and female aged =19 years
- Histologically diagnosed with CD20-expressing B-cell NHL
-Diffuse large B-cell lymphoma (DLBCL)
- Transformed follicular lymphoma
- Relapse after or failure to respond to at least prior treatment
regimen treatments and last dose administered must be more than
2-weeks ahead from enrollment
- Should have received anti-CD20 based chemotherapy previously
- Failed to at least two lines of therapy if patient is candidate for
autologous stem cell transplantation
- Failed frontline therapy if patient is ineligible for autologous stem
cell transplantation.
?Not eligible if patient's IHC expression is both BCL6(-) and MYC(+).
However, in the salvage cohort group, subjects with previous
pathological test results of BCL6(-) and MYC(+) may be eligible.
?Measurable disease, defined as at least one bi-dimensionally
measurable nodal lesion, defined as > 1.5 cm in its longest dimension,
or at least one bi-dimensionally measurable extranodal lesion, defined
as > 1.0 cm in its longest dimension.
?Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2
?Adequate liver, hematological and renal function.
- Total bilirubin = 2 x ULN and AST, ALT = 3 x ULN
- WBC = 3,000 /µL, ANC = 1,000 /µL, Platelets = 75,000 /µL, and
Hemoglobin = 9.0 g/dL. (adjustment with blood transfusion & G-CSF
within 2 weeks is not allowed)
- Cr = 1.5 x ULN or CLcr = 30 mL/min (Cockcroft-Gault)
- Negative test results for Hepatitis C virus (HCV) antibody.
?Negative test results for human immunodeficiency virus (HIV).
- Sexually active women of childbearing potential (WOCPB)
should have 2 negative urine hCG tests before administration
of the study intervention. Tests should be conducted every
week for the first month of the study, then every 4 weeks
thereafter, or every two weeks in case of irregular
menstruation. Urine hCG tests should be performed through 4
weeks after the last dose of glofitamab, poseltinib, or
lenalidomide, whichever comes later. WOCPB should use 2
contraceptive methods, including at least 1 highly effective
contraceptive method, for 4 weeks before the first dose,
during the treatment period, 4 weeks after the last dose of
poseltinib and lenalidomide, 2 months after the last dose of
glofitamab, and 18 months after the last dose of
obinutuzumab. Women who is menopause (no menstruation for at
least 12 months, not related to drug) or surgically sterile
(have no ovaries or no uterus or neither) are not required to
undergo pregnancy tests. Sexually active men should use
condoms during the treatment period and until 4 weeks after
the last dose of poseltinib and lenalidomide, 2 months after
the last dose of glofitamab, and 3 months after the last dose
of obinutuzumab.
?Willing and able to participate in all required evaluations
and procedures in this study protocol including swallowing
capsules.
- Is able to understand the purpose and risks of the study
and to authorize the use of his/her medical information
for the purpose of the study.
2. Exclusion Criteria
1. Has previously received 4 or more lines of anticancer chemotherapies (autologous
hematopoietic stem cell transplantation is considered as 1 line of treatment).
2. Has current evidence or history of macrophage activation syndrome/hemophagocytic
lymphohistiocytosis (MAS/HLH).
3. Prior treatment with glofitamab.
4. Has acute bacterial, viral, or fungal infections confirmed with positive blood culture
or diagnosed clinically in case there is no positive blood culture.
5. Has known active infection or reactivation of latent infection, regardless of
bacteria, viruses, fungi, mycobacteria, or other pathogens, or has an episode of major
infection requiring hospitalization or intravenous antibiotic treatment within 4 weeks
from the dose of study drug.
6. Has received systemic immunotherapy including a radioimmunoconjugate, an antibody-drug
conjugate, or an immune checkpoint inhibitor (eg. anti-cytotoxic
T-lymphocyte-associated protein 4 [anti-CTLA4], anti-programmed death 1 [anti-PD1],
and anti-programmed death ligand 1 [anti-PDL1]) within 4 weeks from the dose of study
drug or within 5 half-lives of the drug.
7. Has experienced treatment-emergent immune-related AE during previous immunotherapy.
8. Has received radiotherapy, anticancer chemotherapy, or other experimental chemotherapy
including chimeric antigen receptor therapy (CAR-T) within 4 weeks from the first dose
of study drug.
9. Has received a homologous hematopoietic stem cell transplantation within 1 year or has
previously received a solid organ transplantation.
10. Has received autologous hematopoietic stem cell transplantation within 100 days from
the first dose of study drug.
11. Has a graft-versus-host disease (GVHD) requiring treatment.
12. Is not able to have oral intake of study drug.
13. Has resistance to BTK inhibitors or lenalidomide (defined as PFS less than 6 months
after BTK inhibitors or lenalidomide).
14. Has previously been diagnosed with a malignancy other than the cancer included in this
study, except appropriately treated basal cell carcinoma, squamous cell skin cancer,
in situ cancer, and at least 5 years of disease free status from previous cancer.
15. Has a clinically significant cardiovascular disease as follows: a heart disease of New
York Heart Association Functional Class III or IV or Objective class C or D, or had
myocardial infarction within 6 months, or has uncontrolled arrhythmia or unstable
angina. Of note, patients with well-controlled and asymptomatic atrial fibrillation
are eligible.
16. Malabsorption syndrome, diseases that seriously affect gastrointestinal function,
resection of the stomach or small intestine that may affect absorption, inflammatory
bowel disease with symptoms, partial or complete intestinal obstruction, or obesity
surgery such as gastric restriction and gastric bypass surgery.
17. Has a history of drug-specific hypersensitivity or anaphylaxis to the study drug
(including active ingredients or excipients).
18. A condition with uncontrolled active bleeding or potential bleeding (e.g., hemophilia
or von Willebrand disease)
19. Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura
(ITP).
20. Requiring treatment with a strong cytochrome P450 (CYP)3A4 inhibitor/inducer.
21. Is receiving or needs to receive warfarin or a corresponding vitamin K antagonist
(e.g., phenprocoumon within 7 days from the first dose of study drug.
22. Prothrombin time (PT)/international normalized ratio (INR) or activated partial
thromboplastin time) (aPTT) (in the absence of lupus anticoagulant) >2x ULN
23. Needs to receive a proton pump inhibitor (e.g., omeprazole, esomeprazole,
lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).Patients receiving proton
pump inhibitors will be eligible after changing regiment to H2-receptor antagonists or
antacids.
24. History of cerebrovascular disease or event including stroke or intracranial
hemorrhage within 6 months prior to the first dose of study drug.
25. Has underwent major surgery within 28 days of the first dose of study drug. Subjects
who underwent major surgery should be properly recovered prior to the first dose of
the drug.
26. Serological status of hepatitis B or hepatitis C: If HBsAg is positive, the subject
may be enrolled if he/she is on appropriate antiviral treatment and HBV DNA is not
detectable. Patients who are HBcAb-positive, HBsAg-negative, and HBV DNA-negative
should receive appropriate antiviral preventive treatment during the study. Patients
who are positive for hepatitis C antibodies should have negative PCR results, and
those with positive PCR results will be excluded. However, the salvage cohort group
does not require preventive treatment. For safety, patients will continue active
anti-HBV treatment with HBV DNA tests performed every 3 months until at least 6 months
after completion of hie/her study participation. HBV DNA will be tested by PCR.
27. Has an active tuberculosis (a history of exposure or a history of positive
tuberculosis testing with clinical symptoms or physical or radiological findings) or a
latent tuberculosis requiring treatment.
28. Has a primary or secondary CNS lymphoma at enrollment.
29. Has active or a history of CNS disease with stroke, epilepsy, CNS vasculitis, or
neurodegenerative disease. Patients with a history of stroke will be eligible if
he/she has been without a stroke or transient ischemic attack in the past 2 years and
no neurological deficits. However, patients with CNS involvement but there is no
relevant CNS disease or patients who have not experienced related symptoms may be
eligible. In addition, if there is CNS involvement, but registration in the main
cohort is possible, registration in the main cohort can be done after discussion with
the state responsible agency. In addition, patients with CNS involvement but there is
possible to register in the main cohort, it can be registered in the main cohort after
discussion with the investigator of mainstudy site.
30. Has a significant and uncontrolled disease that may affect compliance with the study
protocol or interpretation of the results, including diabetes, lung disease, and
autoimmune diseases.
31. Has received attenuated live vaccine within 4 weeks prior to the first dose of study
drug, or is expected to require attenuated live vaccine during the study.
32. Has received systemic immunosuppressive drugs (including, but not limited to,
cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis
factor agents) within 2 weeks prior to the first dose of study drug. Prednisone = 25
mg/day or equivalent corticosteroid treatment is allowed.
33. Has a history of autoimmune disease, including but not limited to myocarditis,
pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis
associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's
syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or
glomerulonephritis. Patients with a medical history of distant past autoimmune
diseases or a current well-controlled autoimmune disease may be enrolled after
discussing and checking with the Monitor.
34. Has diseases in which the use of the study drug is contraindicated or other illness,
metabolic disorders, physical examination findings, or clinical examination findings
with suspected such conditions.
35. Is breastfeeding or pregnant.
36. Is participating in another therapeutic clinical trials.
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