Orelabrutinib Combined With Obinutuzumab and Lenalidomide (OGL Regimen) as First-line Treatment for Marginal Zone Lymphoma.

Official title

Orelabrutinib Combined With Obinutuzumab and Lenalidomide (OGL Regimen) as First-line Treatment for Marginal Zone Lymphoma：a Multicenter Prospective Single Arm Trial

Overview

This is a multicenter prospective single arm phase II study, and the purpose of this study is to evaluate the safety and efficacy of orelabrutinib combined with obinutuzumab and lenalidomide in untreated marginal zone lymphoma. The primary objective was the best complete response rate (CRR).

Detailed description

Marginal zone lymphomas (MZL) are a type of lymphoma that originates from the marginal zone tissue of the lymphoid follicles (Mucosa-associated lymphoid tissue, MALT), and include three subtypes: MALT lymphoma, nodal MZL, and splenic MZL. The incidence of MZL is second only to diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), accounting for approximately 7.8% of all non-Hodgkin lymphomas (NHL). MZL is considered an indolent lymphoma, with patients generally having a better overall survival prognosis. Despite this, some patients still face the challenges of disease relapse or transformation into large cell lymphoma, leading to a poor prognosis.

We conduct this prospective, phase II, single-arm clinical study to initially explore the efficacy and safety of Orelabrutinib combined with obinutuzumab and lenalidomide in patients with previously untreated marginal zone lymphoma. The patients will be treated with 6 cycles of OGL regimen. Patients with CR/PR after 6 cycles of OGL treatment will be treated with 6 cycles of single-agent orelabrutinib regimen.

Interventions

• Drug Orelabrutinib, obinutuzumab, lenalidomide
  Orelabrutinib: 150mg qd d1-d21/C1-C6 obinutuzumab: 1000mg iv d1,d8,d15/c1, 1000mg iv d1/C2-C6 lenalidomide：25mg po qd d1-14/C1-C6 Orelabrutinib: 150mg qd d1-d28/C7-C12

Primary outcome measures

• the best complete response rate [Time frame: At the end of cycle 12(the first 6 cycles are 21 days each, and the following 6 cycles are 28 days each)]

Secondary outcome measures (8)

• ORR [Time frame: At the end of therapy(up to 42 weeks)]
• CRR [Time frame: At the end of therapy(up to 42 weeks)]
• The best ORR [Time frame: At the end of cycle 12(the first 6 cycles are 21 days each, and the following 6 cycles are 28 days each)]
• 2 years progression-free survival Progression free survival (PFS) [Time frame: From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years]]
• 2 years overall survival [Time frame: From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years]]
• TTR [Time frame: Up to 2 years]
• Duration of Response (DOR) [Time frame: Up to 2 years]
• The occurrence of adverse events and serious adverse events [Time frame: One month after the end of treatment（up to 46 weeks）]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years, either sex.
• Histopathologically confirmed B-cell non-Hodgkin lymphoma MZL (splenic, nodal, or extra-nodal).
• At least 1 measurable lesion
• Eligible for treatment: meets the GELF criteria, or has clinical symptoms/organ dysfunction related to the disease
• Patients who are not suitable for local radiotherapy or whose condition progresses after local treatment, and those not suitable for local radiotherapy include the following situations:

• Ann Arbor non-continuous Stage II or Stage III-IV non-gastric MALT and nodal MZL
• SMZL (Splenic Marginal Zone Lymphoma)
• Gastric MALT with Lugano Stage II2/IIE/IV
• ECOG performance status (PS) score of 0-2.
• Expected survival time is ≥3 months
• Sign the Informed consent

Exclusion criteria

• Currently has other malignant tumors;
• Lymphoma involving the central nervous system
• Allergic to any of the study drugs;
• Active infection or uncontrolled HBV infection (DNA\>105/ml), HIV/AIDS, or other severe infectious diseases;
• Pregnant or lactating women and women of childbearing age who are unwilling to use contraception;
• Any other conditions deemed unsuitable for participation in this trial by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking Union Medical College Hospital — Beijing

Publications

• Sharp J, Shana'ah AY, Voorhees TJ, Bond DA, Sawalha Y, Sigmund A, Hanel W, Sehgal L, Alinari L, Baiocchi R, Maddocks K, Jones D, Christian B, Epperla N. Resistance Mechanism for Zanubrutinib in Marginal Zone Lymphoma. J Natl Compr Canc Netw. 2025 Jun 23;23(7):e257045. doi: 10.6004/jnccn.2025.7045. PMID 40550489

Identifiers

NCT: NCT06454968 · PUMCH-NHL-017

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗