Obinutuzumab Combined With Lenalidomide(GL) in Recurrent or Refractory Marginal Zone Lymphoma (MZL)
Study Details
Study Description
Brief Summary
This is a prospective, multi-center clinical study to enroll 59 patients with relapsed and refractory MZL. The study was designed to assess the efficacy and safety of the combination of obintuzumab and lenalidomide in the treatment of relapsed and refractory(R/R) marginal zone lymphoma (MZL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Marginal zone lymphoma(MZL) is incurable, the vast majority of MZL patients eventually will face disease relapsing or progression .
There is no standard second-line treatment for relapsed/refractory MZL, and the synergistic effect of obintuzumab and lenalidomide had been verified in other indolent lymphomas.
This trial is designed to investigate the efficacy and safety of the combination of obintuimab(GA101) and lenalidomide(GL therapy) in R/R marginal zone lymphoma, in order to find a safe and effective option in this type of disease.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LG(Obintuzumab and lenalidomide ) Arm Obintuzumab(GA101), lenalidomide Patients were treated with obintuzumab and lenalidomide for 6 cycles as induction, then followed by 2-year- maintenance |
Drug: Obinutuzumab, lenalidomide
The treatment is divided into two phases: induction therapy and maintenance therapy
Induction: 6 cycles, every 28 days/cycle
Lenalidomide: 20 mg/day, oral. Dosing on Days 2-22 of Cycles 1-6
Obinutuzumab pegol: 1000 mg each time, administered on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6. ( 8 total infusions)
Maintenance: Patients who achieved at least a partial response after 6 months of induction therapy were eligible to enter the maintenance phase for 2 years
During the first year of maintenance therapy, patients received obinutuzumab (1000 mg on Day 1 of each 28-day cycle, every 2 cycles for 6 infusions) and lenalidomide (10 mg on Days 2-22 of each 28-day cycle, 12 cycles) until disease progression or end of treatment
During the second year of maintenance therapy, patients received rituximab (6 infusions of 1000 mg) every 2 cycles (28 days each) until disease progression or end of treatment
Other Names:
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Outcome Measures
Primary Outcome Measures
- Overall Remission Rate(ORR) [24 weeks]
Disease response evaluation after 6 cycles will be used to determine the overall remission rate
Secondary Outcome Measures
- 2-year Progression Free Survival (PFS24): [up to 4.5 years]
Progression-Free Survival will be measured according to the Cheson 2007 criteria. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.
- 2-year Event-Free Survival (EFS24) [up to 4.5 years]
Event-Free Survival will be measured from the date of inclusion to the date of first documented disease progression, relapse, initiation of new anti-lymphoma therapy or death from any cause.
- Complete Response Rate (CR) [24 weeks]
Disease response evaluation after 6 cycles will be used to determine the overall remission rate
- Overall survival (OS) [up to 4.5 years]
Overall survival will be measured from the date of inclusion to the date of death from any cause. Alive patients will be censored at their last date known to be alive
Eligibility Criteria
Criteria
Inclusion Criteria:
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The patient voluntarily agreed to participate in the study, signed the informed consent form and complied with the study protocol
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Age ≥18 years
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Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
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Histologically confirmed MZL. For splenic marginal zone lymphoma (SMZL) for which histological specimens of the spleen are not available, it is required to meet the minimum diagnostic criteria for SMZL and exclude any other type of small B-cell lymphoma, that is, it is required to have a definite diagnosis of MZL
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Prior treatment with at least one line of systemic lymphoma including prior immunotherapy or chemoimmunotherapy
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At least one bi-dimensionally measurable nodal lesion (> 1.5 cm in greatest diameter on CT scan or MRI) OR at least one bi-dimensionally measurable extranodal lesion (> 1.0 cm in greatest diameter on CT scan or MRI)
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Need for systemic therapy as assessed by the investigator based on tumor size and/or GELF criteria
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Life expectancy ≥ 3 months
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Adequate blood function (except for abnormalities considered by the investigator to be due to the underlying disease of lymphoma), defined as follows:
Hemoglobin ≥ 7 g/dL Absolute neutrophil count ≥ 1.0 × 109/L Platelet count ≥ 50 x 109/L
- Normal laboratory values:
Creatinine clearance ≥ 30 mL/min measured or estimated according to institutional standard methods AST or ALT ≤ 2.5 x upper limit of normal (ULN) Serum bilirubin ≤ 2 × ULN (≤ 3 × ULN in patients with Gilbert's syndrome)
-
For men who are not surgically sterile: Agree to use barrier contraception during treatment and for at least 3 months after the last dose of obinutuzumab or lenalidomide or as required by institutional guidelines, whichever is longer. In addition, male patients must agree to have their partner use an alternative method of contraception (e.g., oral contraceptive, intrauterine device, barrier method, or spermicide)
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For women who are not surgically sterile: use two appropriate methods of contraception, such as oral contraceptives, intrauterine device, or barrier methods, in combination with spermicide for at least 28 days prior to agreeing to start of study medication, during treatment and for at least 12 months after the last dose of either obinutuzumab or lenalidomide, or as required by institutional guidelines, whichever is longer -
Exclusion Criteria:
-
Patients who were refractory or resistant to lenalidomide or obinutuzumab, refractory was defined as no response (PR or CR) after the start of treatment, or relapse within 6 months (≤ 2 cycles of prior lenalidomide or obinutuzumab and no exclusion of treatment change for non-refractory reasons)
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History of serious allergic or anaphylactic reactions to monoclonal antibody therapy
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Known hypersensitivity to any of the study drugs
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Known sensitivity to murine products
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Previous ≥ Grade 3 allergic reactions/Hypersensitivity to thalidomide
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History of erythema multiforme, Grade 3 rash, or blisters following prior immunomodulatory derivative therapy
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Histologically transformed, highly malignant or diffuse large B-cell lymphoma
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Central nervous system or meningeal involvement by lymphoma
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Contraindications for the investigational medical product included in the study treatment regimen
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Positive test for chronic hepatitis B infection (defined as positive HBsAg serology)
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Hepatitis C positive (hepatitis C virus antibody serology)
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HIV or Human T-Lymphocytic Leukemia Virus 1 (HTLV1) positive
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Evidence of any serious, uncontrolled co-morbidities that could affect compliance with the protocol or interpretation of results, including but not limited to significant cardiovascular disease (e.g., New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmias, or unstable angina), or significant pulmonary disease (including history of obstructive pulmonary disease or bronchospasm)
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Infection caused by known active bacteria, viruses, fungi, or other microorganisms (other than fungal infection of the nail bed), or any major infection requiring intravenous antibiotics or hospitalization (completion of the entire course of antibiotics, except for neoplastic fever) within 4 weeks prior to enrollment
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Prior malignancy other than lymphoma, unless the subject has a disease-free survival of ≥ 5 years
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Pregnant or lactating women.
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Have ≥ Grade 2 neuropathy
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Participation in another clinical trial using a pharmacological intervention during the trial or within 28 days prior to Cycle 1
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Corticosteroids within 4 weeks of enrollment, unless administered at a dose equivalent to ≤ 30 mg/day prednisone (within 4 weeks)
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Past history of progressive multifocal leukoencephalopathy (PML)
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Live vaccines within 28 days of treatment start
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History of solid organ transplantation
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Presence of any serious illness or abnormality in the clinical laboratory test results that, in the opinion of the investigator, would make the patient unable to safely participate and complete this study, or affect protocol compliance or interpretation of results
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institute of Hematology & Blood Diseases Hospital | Tianjin | Tian | China | 300020 |
Sponsors and Collaborators
- Institute of Hematology & Blood Diseases Hospital
Investigators
- Principal Investigator: Shuhua Yi, Dr, Institute of Hematology & Blood Diseases Hospital, Chinese
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BDHMZL2023