Obinutuzumab Combined With Bendamustine in the Treatment of Mature B-cell Lymphoma

Obinutuzumab Combined With Bendamustine in the Treatment of Mature B-cell Lymphoma: an Open-label, Multicenter Study

This is a prospective, single-center, single-arm clinical study to evaluate the efficacy and safety of maintenance therapy with obinutuzumab for 2 years in patients ≥ 18 years of age with newly diagnosed mature B-cell lymphoma (including follicular lymphoma[FL], marginal zone cell lymphoma[MZL] , waldenström macroglobulinemia[WM], hairy-cell leukemia variant[HCL-v]) who achieved ≥ PR after 6 cycles of obinutuzumab in combination with bendamustine.

Study Overview

• Status: Recruiting
• Conditions: B Cell Lymphoma
• Intervention / Treatment: Drug: Obinutuzumab Combined With Bendamustine

Detailed Description

This study will explore whether induction therapy with obinutuzumab in combination with bendamustine followed by maintenance therapy with obinutuzumab in treatment-naïve patients with mature B-cell lymphoma will improve the prognosis of patients with this type of indolent mature B-cell lymphoma and the efficacy and safety of this regimen in different lymphoma subtypes.

• Study Type: Interventional
• Enrollment (Estimated): 134
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shuhua Yi, Dr; Phone Number: 86-22-23909106; Email: yishuhua@ihcams.ac.cn
• Study Contact Backup: Name: Lugui Qiu, Dr; Phone Number: 86-22-23909172; Email: qiulg@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences
      • Contact: Yuting Yan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients voluntarily participate in this study, sign informed consent and comply with the study trial protocol
2. Age ≥ 18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
4. FL (grade 1 - 3a), MZL, WM, HCL-v with histological documentation of CD20 positivity
5. Systemic therapy as assessed by the investigator based on tumor size and/or GELF criteria
6. Histological confirmation of MZL. For splenic marginal zone lymphoma (SMZL) for which splenic histological specimens cannot be obtained, it is required to meet the minimum diagnostic criteria for SMZL and rule out any other type of small B-cell lymphoma, that is, it is required to confirm the diagnosis of MZL. If the patient had gastric extranodal MZL with symptoms: H. pylori-negative primary lesion or re-lesion after local therapy (i.e., surgery or radiation therapy), the investigator judged whether treatment was required, and if H. pylori-positive, stable disease, progression, or recurrence after antibiotic treatment, the investigator judged whether treatment was required
7. Waldenström macroglobulinemia,lymphoplasmacytic lymphoma,WM/LPL(WM/LPL): meets the diagnostic criteria for WM/LPL and is indicated for treatment (meets at least one of the following conditions): symptomatic hyperviscosity; symptomatic peripheral neuropathy; amyloidosis; cold agglutinin disease; cryoglobulinemia; disease-related cytopenias (Hb < 100 g/L, PLT < 100 × 109/L); giant lymph nodes; those with systemic symptoms: persistent for two weeks/recurrent fever (above 38℃) and not caused by infection, or night sweats and/or weight loss > 10% within 6 months; rapid disease progression, such as lymph node enlargement of more than 50% within 2 months, and/or absolute doubling time of peripheral blood lymphocytes < 6 months, and/or rapid decrease in hemoglobin or platelets due to non-autoimmune causes
8. HCL-v: Meet the WHO diagnostic criteria (4th Edition, 2016), and treatment is indicated
9. At least one two-dimensional measurable lymph node lesion (maximum diameter > 1.5 cm by CT scan or MRI), or at least one two-dimensional measurable extranodal lesion (maximum diameter > 1.0 cm by CT scan or MRI)
10. Life expectancy ≥ 3 months
11. 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 × 10^9/L platelet count ≥ 50 × 10^9/L
12. Normal laboratory values: creatinine clearance ≥ 30 mL/min AST or ALT ≤ 2.5 x upper limit of normal (ULN) Serum bilirubin ≤ 2 x ULN (≤ 3 x ULN for patients with Gilbert's syndrome) measured or estimated according to institutional standard methods
13. 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 otuzumab or bendamustine or as required by guidelines established by the institution, 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)
14. For women who are not surgically sterilized: agree to use two appropriate methods of contraception, such as oral contraceptives, intrauterine devices, or barrier methods, with spermicide for at least 28 days before starting study drug, during treatment, and for at least 12 months after the last dose of otuzumab or bendamustine, or for the time required by the guidelines established by the study institution (whichever is longer)

Exclusion Criteria:

1. Mature B-cell lymphoma previously treated with chemotherapy, immunotherapy, or radiation therapy
2. Evidence of aggressive NHL transformation
3. Known hypersensitivity to any study drug
4. Known sensitive to murine products
5. Central nervous system or meningeal involvement by lymphoma
6. Contraindications to the investigational drug included in the study treatment regimen
7. Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology)
8. Hepatitis C positive (hepatitis C virus [HCV] antibody serology)
9. HIV or Human T-Lymphocytic Leukemia Virus 1 (HTLV1) positive
10. Evidence of any serious, uncontrolled co-morbidities that could affect compliance with the study 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);
11. Infection caused by known active bacteria, viruses, fungi, or other microorganisms (except 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
12. Previous history of malignancy other than lymphoma, unless the subject has a disease-free survival of ≥ 5 years
13. Pregnant or lactating women.
14. Participated in other clinical trials using drug interventions during the trial or within 28 days prior to Cycle 1 Corticosteroids within 4 weeks of enrollment, unless administered at a dose equivalent to ≤ 30 mg/day prednisone (within 4 weeks)

16. Past history of progressive multifocal leukoencephalopathy (PML) Vaccination with live vaccines within 28 days prior to start of treatment 18. History of solid organ transplantation 19. Presence of any serious disease or abnormality in the clinical laboratory test results that, in the opinion of the investigator, could make the patient unable to safely participate in and complete this study, or affect protocol compliance or interpretation of results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Obinutuzumab Combined With Bendamustine

Drug: Obinutuzumab Combined With Bendamustine; The treatment is divided into two phases: induction therapy and maintenance therapy Induction therapy: 6 cycles of obinutuzumab (1000 mg, IV) on Days 1, 8, and 15 of Cycle 1 and on Day 1 of Cycles 2-6 (28 days/cycle). Bendamustine (90 mg/m2, IV) on Days 1 and 2 of Cycles 1-6. Maintenance therapy: Patients who achieved at least a partial response after 6 months of induction therapy were eligible to enter the maintenance phase, during which obinutuzumab (1000 mg, IV) was administered every 2 months for 2 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Remission Rate(ORR)	Disease response evaluation after 6 cycles will be used to determine the overall remission rate	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression free survival is defined as the time from the day in which the patient is enrolled to the date on which tumor progresses or the date on which the patient dies for any cause. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.	up to 4.5 years
Event-Free Survival	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.	up to 4.5 years
Complete Response Rate	Disease response evaluation after 6 cycles will be used to determine the overall remission rate	24 weeks
Overall survival	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	up to 4.5 years

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Shuhua Yi, Dr, Institute of Hematology & Blood Diseases Hospital, Chinese

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2023
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: March 4, 2024
• First Submitted That Met QC Criteria: May 10, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Obinutuzumab; Bendamustine
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Bendamustine Hydrochloride; Obinutuzumab
• Other Study ID Numbers: BDHBcell2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No