Clinical trial NCT05846750: Obinutuzumab in Combination With Lenalidomide in Relapsed or Refractory Marginal Zone Lymphoma
Official title: A Prospective, Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of Obinutuzumab(GA101) in Combination With Lenalidomide in Relapsed and Refractory(R/R) Marginal Zone Lymphoma (MZL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Marginal Zone Lymphoma
Keywords: Obinutuzumab
Lenalidomide
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2023-05-06
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective, multicenter clinical study that will enroll 59 patients with relapsed and refractory (R/R) MZL. The study is designed to evaluate the efficacy and safety of the combination of obinutuzumab and lenalidomide in the treatment of relapsed and refractory marginal zone lymphoma (MZL).

Detailed description: Marginal zone lymphoma (MZL) is incurable, and the vast majority of patients with MZL eventually face disease relapse or progression.

There is no standard second-line treatment for relapsed/refractory MZL, and the synergistic effect of obinutuzumab and lenalidomide has been demonstrated in other indolent lymphomas.

The aim of this trial is to investigate the efficacy and safety of the combination of obinutuzumab (GA101) and lenalidomide in the treatment of R/R marginal zone lymphoma in order to find a safe and effective option for this type of disease.

Eligibility criteria: Inclusion Criteria:

1. Signed Informed Consent Form
2. Age ≥18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
4. Histologically confirmed MZL. have a definite diagnosis of MZL
5. Prior treatment with at least one line of systemic lymphoma including prior immunotherapy or chemoimmunotherapy
6. 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)
7. Need for systemic therapy as assessed by the investigator
8. Life expectancy ≥ 3 months
9. 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
10. Normal laboratory values:

    Creatinine clearance ≥ 30 mL/min; Glutathione transaminase(AST) or glutathione aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN); Serum bilirubin ≤ 2 × ULN (≤ 3 × ULN in patients with Gilbert's syndrome)
11. 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)
12. 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:

1. Patients who are refractory or resistant to lenalidomide or obinutuzumab, refractory is 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)
2. History of serious allergic or anaphylactic reactions to monoclonal antibody therapy
3. Known hypersensitivity to any of the study drugs
4. Known sensitivity to murine products
5. Previous ≥ Grade 3 allergic reactions/Hypersensitivity to thalidomide
6. History of erythema multiforme, Grade 3 rash, or blisters following prior immunomodulatory derivative therapy
7. Histologically transformed, highly malignant or diffuse large B-cell lymphoma
8. Central nervous system or meningeal involvement by lymphoma
9. Contraindications for the investigational medical product included in the study treatment regimen
10. Positive test for chronic hepatitis B infection (defined as positive HBsAg serology)
11. Hepatitis C positive (hepatitis C virus antibody serology)
12. HIV or Human T-Lymphocytic Leukemia Virus 1 (HTLV1) positive
13. Evidence of any serious, uncontrolled co-morbidities that 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)
14. 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
15. Prior malignancy other than lymphoma, unless the subject has a disease-free survival of ≥ 5 years
16. Pregnant or lactating women.
17. Have ≥ Grade 2 neuropathy
18. Participation in another clinical trial using a pharmacological intervention during the trial or within 28 days prior to Cycle 1
19. Corticosteroids within 4 weeks of enrollment, unless administered at a dose equivalent to ≤ 30 mg/day prednisone (within 4 weeks)
20. Past history of progressive multifocal leukoencephalopathy (PML)
21. Live vaccines within 28 days of treatment start
22. History of solid organ transplantation
23. 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

Primary outcomes:
measure: Overall Remission Rate(ORR)
timeFrame: 24 weeks
Secondary outcomes:
measure: 2-year Progression Free Survival (PFS24):
timeFrame: up to 4.5 years
measure: 2-year Event-Free Survival (EFS24)
timeFrame: up to 4.5 years
measure: Complete Response Rate (CR)
timeFrame: 24 weeks
measure: Overall survival (OS)
timeFrame: up to 4.5 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tian
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, Chinese
name: Shuhua Yi, Dr
role: PRINCIPAL_INVESTIGATOR
References: