Clinical trial NCT06454968: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Marginal Zone Lymphoma
Keywords: Orelabrutinib
Marginal Zone Lymphoma
obinutuzumab
lenalidomide
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2024-06-12
Enrollment: 45
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 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.

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\&gt;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.

Primary outcomes:
measure: the best complete response rate
timeFrame: At the end of cycle 12(the first 6 cycles are 21 days each, and the following 6 cycles are 28 days each)
Secondary outcomes:
measure: ORR
timeFrame: At the end of therapy(up to 42 weeks)
measure: CRR
timeFrame: At the end of therapy(up to 42 weeks)
measure: The best ORR
timeFrame: At the end of cycle 12(the first 6 cycles are 21 days each, and the following 6 cycles are 28 days each)
measure: 2 years progression-free survival Progression free survival (PFS)
timeFrame: 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]
measure: 2 years overall survival
timeFrame: From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years]
measure: TTR
timeFrame: Up to 2 years
measure: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: The occurrence of adverse events and serious adverse events
timeFrame: One month after the end of treatment（up to 46 weeks）
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: