A Exploratory Study on Untreated Follicular Lymphoma With Orelabrutinib, Tafasitamab, and Lenalidomide (CUREMZL002)

A Multicenter Exploratory Clinical Study on the Treatment of Untreated Follicular Lymphoma With Orelabrutinib, Tafasitamab, and Lenalidomide

Evaluate the efficacy and safety of orelabrutinib, tafasitamab, and lenalidomide in the first-line treatment of patients with follicular lymphoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Follicular Lymphoma
• Intervention / Treatment: Drug: Orelabrutinib; Drug: Tafasitamab; Drug: Lenalidomide

Detailed Description

Follicular lymphoma (FL) is the most common indolent non-Hodgkin's lymphoma (NHL), accounting for 35% of NHL cases . The median age at diagnosis is 65 years , and most patients are diagnosed at an advanced stage. Although FL is still considered incurable, the clinical prognosis for most patients remains favorable.Currently, there is some data available for BTKi and tafasitamab in relapsed/refractory follicular lymphoma, and further exploration of relevant data in the first-line setting is needed. This combination therapy may provide new options for patients with follicular lymphoma.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shuhua Yi, Dr; Phone Number: +86-022-23909106; Email: yishuhua@ihcams.ac.cn

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China
      • Shenzhen Second People's Hospital
      • Contact: xiaoqing Li; Phone Number: 18620385718
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330000
      • The First Affiliated Hospital of Nanchang University
  • Shandong
    • Jinan, Shandong, China
      • Qilu Hospital of Shandong Province
      • Contact: jingjing Ye; Phone Number: 18560086995
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300020
      • Institute of Hematology & Blood Diseases Hospital, China

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age > 18 years, regardless of gender;
2. Newly diagnosed patients with follicular lymphoma (Grade 1, 2, or 3a) confirmed histologicallyaccording to the World Health Organization (WHO) classification of diseases;
3. Deemed by the investigator to have an indication for treatment and require therapy;
4. ECOG performance status score of 0-2;

5. Laboratory tests meeting the following criteria:

   1. Bone marrow hematopoietic function is essentially normal: WBC 3.5x10^9/L, ANC > 1.0x10^9/L, PLT > 75x10^9/L, Hb > 80 g/L;
   2. Liver function: AST/ALT s 2xULN, TBILI s 2xULN;
   3. Renal function: Creatinine clearance rate > 50 ml/min;6. Presence of at least one measurable lesion: Lymph node lesion with a long diameter > 1.5 cm orextranodal lesion with a long diameter > 1.0 cm as shown by PET/CT, CT, or MRl, or a lesion > 2cm assessed by clinical examination;

7. Ability to provide written informed consent.

Exclusion Criteria:

1. Women with a positive serum pregnancy test or who are breastfeeding;
2. Patients with lymphoma involving the central nervous system (CNS);
3. Clinically significant heart disease, including unstable angina, acute myocardial infarction within6 months prior to randomization, congestive heart failure with New York Heart Association(NYHA) functional class IIl or IV, or left ventricular ejection fraction <50%;
4. Patients with grade >2 neuropathy;
5. Patients with active hepatitis B (HBV, hepatitis C (HCV, or other acquired/congenitalimmunodeficiency diseases;
6. Patients with severe active infections requiring systemic antibiotic treatment;
7. Patients with a history of severe neurological or psychiatric disorders that impair trialparticipation, including dementia, epilepsy, severe depression, and mania;8. Drug abuse, or medical, psychological, or social conditions that may interfere with studyparticipation or result evaluation;

9. Patients deemed ineligible by the investigator.

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: Orelabrutinib Tafasitamab Lenalidomide; Orelabrutinib tafasitamab Lenalidomide

Drug: Orelabrutinib; Orelabrutinib 150 mg orally once daily on Days 1-28 of each 28-day cycle during induction therapy and maintenance therapy.; Drug: Tafasitamab; Tafasitamab 12 mg/kg administered by intravenous infusion on Days 1, 4, 8, 15, and 22 in Cycle 1; on Days 1, 8, 15, and 22 in Cycles 2-3; and on Days 1 and 15 from Cycle 4 onward during induction therapy.; Drug: Lenalidomide; Lenalidomide 20 mg orally once daily on Days 1-21 of each 28-day cycle during induction therapy and 10 mg orally once daily on Days 1-21 of each 28-day cycle during maintenance therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Percentage of participants achieving a Complete Response (CR) or Partial Response (PR) at the end of cycle 12, assessed according to the Lugano 2014 classification	At the end of cycle 12 (each cycle is 28 days; up to approximately 48 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response (CR) Rate	The complete response (CR) rate is defined as the percentage of participants who achieve a complete response at the end of cycle 12 , as assessed by the investigator according to the Lugano 2014 classification criteria	At the end of cycle 12 (each cycle is 28 days; up to approximately 48 weeks)
Progression-Free Survival (PFS)	The time from the start of treatment to disease progression or death from any cause.	Up to approximately 3 years
Rate of Progression of Disease within 24 Months (POD24)	Percentage of participants experiencing disease progression within 24 months from the initiation of treatment	24 months
Incidence and Severity of Adverse Events (AEs)	Safety evaluated by monitoring the incidence and severity of AEs, graded according to the NCI CTCAE v5.0.	Up to approximately 3 years
Overall Survival (OS)	The time from the start of treatment to death from any cause.	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: April 13, 2026
• First Submitted That Met QC Criteria: May 10, 2026
• First Posted (Actual): May 14, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: lenalidomide; orelabrutinib; tafasitamab
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Follicular; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; tafasitamab; orelabrutinib
• Other Study ID Numbers: IIT2026026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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