GPL in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma
Study Details
Study Description
Brief Summary
Prospective, open-ended, single-arm, multicenter Phase II clinical trial. To evaluate the efficacy of Glofitamab, Poseltinib, and Lenalidomide combination therapy in patients with relapsed/refractory diffuse large B-cell lymphoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
For outpatients or inpatients who meet the criteria for subject selection, the study is conducted with patients who have given a sufficient explanation of the study and who voluntarily consented to participate in the study.
Patients enrolled in the study receive a combination therapy of glofitamab, poseltinib, and lenalidomide according to the criteria specified in the protocol.
This therapy is defined as one cycle of 3 weeks, and a total of 12 cycles is planned.
glofitamab is administered in steps. 2.5 mg on the 8th day of Cycle 1, 10 mg on the 15th day, 30 mg on the 1st day of Cycle 2, and then 30 mg intravenously on the 1st day of each cycle.
poseltinib is administered orally at 40 mg BID daily from Day 1 to Day 21 of each cycle, and lenalidomide is administered orally at 30 mg QD daily from Day 1 to Day 14 of each cycle.
Maintenance therapy is offered with poseltinib and lenalidomide only for patients with a partial response (PR) or complete response (CR).
In addition, this study includes a salvage protocol for patients with CNS (central nerve system) lesions during patient recruitment.
These patients are excluded from treatment with glofitamab because of the potential risk of CNS toxicity and will receive only poseltinib plus lenalidomide.
The first 3+3 patients will proceed to a safety cohort, with dose adjustments for lenalidomide and poseltinib. These 6 persons were not included in the cohort evaluating the outcome of the study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment total 2years. Glofitamab: Increase from 2.5mg for 8days in 1 cycle to 10mg for 15days. 2cycles 1day 30mg, 30 mg on the 1st day of every week thereafter. Poseltinib: 40mg/day bid orally, administered daily from the 1st to the 21st of every week. Lenalidomide: 20mg/day bid orally, administered daily from the 1st to the 14st of every week. |
Drug: Glofitamab, Poseltinib, Lenalidomide
Glofitamab: Increase from 2.5mg for 8days in 1 cycle to 10mg for 15days. 2cycles 1day 30mg, 30 mg on the 1st day of every week thereafter. Poseltinib: 40mg/day bid orally, administered daily from the 1st to the 21st of every week.
Lenalidomide: 20mg/day bid orally, administered daily from the 1st to the 14st of every week.
|
Outcome Measures
Primary Outcome Measures
- Efficacy evaluation of Gofitamab, Poseltinib, and Lenalidomide using endpoints [At the end of Cycle 2 (each cycle is 28 days)]
Overall Response Rate according to Lugano criteria
Eligibility Criteria
Criteria
Inclusion Criteria:
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Men and women 19 years of age and older
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Histologically diagnosed B-cell Non-Hodgkin's Lymphoma, which is expected to express CD20
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Diffuse large B-cell lymphoma(DLBCL)
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(Transformed follicular lymphoma)
- Patients whose previous treatment failed or relapsed after the previous treatment, and the last medication was 2 weeks or more before the registration.
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Must have previously received anti-CD20-based treatment.
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If the patient is a candidate for autologous hematopoietic stem cell transplantation, at least two therapies have failed.
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If the patient is not suitable for autologous hematopoietic stem cell transplantation, at least one therapy has failed.
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If the patient's immunohistochemistry result is BCL6(-) and MYC(+), it is not suitable
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Two-dimensionally measurable nodal lesion with the longest length of 1.5 cm at least one or more, or two-dimensionally measurable extranodal lesion with the longest length of 1.0 cm at least one or more
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Eastern Cooperative Oncology Group is 0,1 or 2
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Adequate liver function, kidney function, hematopoietic function
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Total bilirubin ≤ 2 x ULN or AST, ALT ≤ 3 x ULN
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WBC ≥ 3,000 /μL, ANC ≥ 1,000 /μL, Platelets ≥ 75,000 /μL, or Hemoglobin ≥ 9.0 g/dL
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Correction by blood transfusion within 2 weeks is not permitted
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Cr ≤ 1.5 x ULN and CLcr ≥ 30 mL/min/1.73m2
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Hepatitis B virus (HBV) infection was negative (hepatitis B surface antigen (HBsAg) negative). In case of latent HBV infection or previous infection (HBsAg negative and hepatitis B core antibody (HBcAb) positive), HBV DNA is not detected. The patient is willing to undergo DNA testing and appropriate antiviral therapy on Day 1 of each cycle and every 3 months for 12 months after the last cycle.
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Hepatitis C virus, HCV is negative.
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Human immunodeficiency virus, HIV is negative.
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Sexually active women of childbearing potential should have two negative urine hCG tests prior to administration of the test drug.
During the first month of the study, a weekly urine test was performed. After that, a urine test should be performed every 4 weeks or every 2 weeks if menstruation is irregular.
Urine hCG testing should be performed until 4 weeks after the last administration of glofitamab, poseltinib, and lenalidomide.
Women of childbearing potential should use two methods of contraception, including at least one highly effective method of contraception 4 weeks before the first treatment, during the treatment period, 4 weeks after the last dose of poseltinib or lenalidomide, 2 months after the last dose of glofitamab, and until 18 months after the last dose of obinutuzumab.
Pregnancy testing is not required for women who are unable to conceive after menopause (at least 12 months of drug-related amenorrhea) or surgically (no ovaries or uterus or both).
Sexually active men should use condoms during treatment and until 4 weeks after the last dose of poseltinib or lenalidomide, 2 months after the last dose of glofitamab, and 3 months after the last dose of obinutuzumab.
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Subjects must be able and willing to participate in all necessary evaluations and procedures of the study protocol, and be able to swallow oral medications without difficulty.
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Subjects must understand the purpose and risks of the study and be able to authorize the use of their medical information for the purpose of the study.
Exclusion Criteria:
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Patients who have previously received 4 or more chemotherapy
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Patients with or with a history of macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH).
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Patients who have previously received Glofitamab.
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A patient with acute bacterial, viral, or fungal infection, confirmed with a positive blood culture test or if there is no positive blood culture test, it is diagnosed by clinical judgment.
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Patients with a known active infection or reactivation of a latent infection, regardless of bacterial, viral, fungal, mycobacterial or other pathogen or patients with major infection episodes requiring hospitalization or intravenous antibiotic treatment within 4 weeks of administration
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Patients who have previously received systemic immunotherapy, radioimmunoconjugates, antibody-drug conjugates, immune checkpoint inhibitors (eg. anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4), Patients who received anti-programmed death 1 (anti-PD1) and anti-programmed death ligand 1 (anti-PDL1) drugs within 4 weeks before administration of the test drug or within 5 half-lives of the drug.
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Patients with a treatment-emergent immune-related AE when using previous immunotherapy
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Patients who received radiation therapy, chemotherapy, or other experimental chemotherapy, including chimeric antigen receptor therapy (CAR-T), within 4 weeks of the first dose of study drug.
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Patients who have received an allogeneic hematopoietic stem cell transplant within 1 year or have previously received a solid organ transplant.
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Patients who received autologous hematopoietic stem cell transplantation within 100 days of the first dose of the study drug
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Patients with graft-versus-host disease (GVHD) requiring treatment
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Patients unable to take oral medications
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Patients resistant to BTK inhibitor or lenalidomide (defined as PFS of less than 6 months to BTK inhibitor and lenalidomide)
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If you have been diagnosed with a malignant disease other than cancer included in this study in the past, provided that basal cell carcinoma, squamous cell skin cancer, and in situ cancer that have been properly treated , and cancers with no disease for more than 5 years are excluded from other malignant diseases.
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Patients with clinically significant cardiovascular disease, with heart disease corresponding to New York Heart Association Functional Class III or IV or Objective class C or D, myocardial infarction within 6 months, uncontrolled arrhythmia or unstable angina patient.
However, patients with well-controlled and asymptomatic atrial fibrillation may be enrolled.
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malabsorption syndrome, diseases that significantly affect the functioning of the gastrointestinal tract; resection of the stomach or small intestine that may affect absorption; symptomatic inflammatory bowel disease, partial or complete intestinal obstruction; Bariatric surgery, such as gastric restriction and gastric bypass surgery
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Patients with a history of drug-specific hypersensitivity or anaphylaxis to the test drug (including active ingredients or excipients)
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Disease with or possibly bleeding uncontrolled, active bleeding (such as hemophilia or von Willebrand disease)
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Autoimmune hemolytic anemia, AIHA or Idiopathic thrombocytopenic purpura (ITP)
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Patients requiring treatment with potent cytochrome P450 3A4 (CYP3A4) inhibitors/inducers
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Patients who need or are taking warfarin or an equivalent vitamin K antagonist (eg phenprocoumon) within 7 days of the first dose of the test drug
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Prothrombin time (PT)/INR or aPTT (in the absence of lupus anticoagulant) >2x ULN
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Patients requiring treatment with a proton pump inhibitor (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).Among patients receiving proton pump inhibitors Patients switching to H2 receptor antagonists or antacids may be enrolled.
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Patients with a history of cerebrovascular disease or events including stroke or intracranial hemorrhage within 6 months prior to the first administration of the test drug
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Patients who underwent major surgery within 28 days of the first dose of the study drug. If the subject undergoes major surgery should be adequately recovered prior to the first administration of the drug.
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Serological status of hepatitis B or hepatitis C: Patients who are both HBcAb-positive and HBsAg-negative should have a negative PCR result. Patients who were HBsAg positive or PCR positive were excluded. HBcAb-positive, HBsAg-negative and PCR-negative patients should receive appropriate antiviral prophylaxis during the study period. A person who is positive for hepatitis C antibody must have a negative PCR result, except for a positive PCR result.
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Patients with active tuberculosis (patients with clinical symptoms or physical or radiological findings with a history of exposure or positive tuberculosis test) or latent tuberculosis requiring treatment.
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Patients with primary or secondary central nervous system (CNS) lymphoma at the time of enrollment.
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Patients with present or past CNS disease with stroke, epilepsy, CNS vasculitis or neurodegenerative disease. Patients with a history of stroke with no neurologic deficits and no stroke or transient ischemic attack in the past 2 years are permitted.
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Patients with significant, uncontrolled medical conditions that could affect compliance with study protocols or interpretation of results, including diabetes, pulmonary disease, and autoimmune disease.
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Patients who received live attenuated vaccine within 4 weeks prior to the first dose of study drug or who are expected to require administration of live attenuated vaccine during the study period.
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Patients receiving 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 less or equivalent corticosteroid therapy is acceptable.
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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 distant history of autoimmune disease or with well-controlled autoimmune disease can be enrolled after discussion and confirmation with the monitor.
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Other diseases suspected of a disease or condition for which the use of the test drug is contraindicated; metabolic disorders; or patients with clinical findings
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breastfeeding or pregnancy
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Participating in other therapeutic clinical trials
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Seoul National University Hospital | Seoul | Korea, Republic of |
Sponsors and Collaborators
- Seoul National University Hospital
Investigators
- Study Director: Sung-soo Yoon, Seoul National University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GPL