Orelabrutinib Combined With Induction Therapy Followed by Sequential Monotherapy Maintenance in MCD Subtype Diffuse Large B-cell Lymphoma

NCT07677813 | Not Yet Recruiting Phase 2

• 1 other identifier: 25K405-001
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, single-arm, prospective study aimed at evaluating the efficacy and safety of orelabrutinib combined with an induction regimen followed by monotherapy maintenance in patients with MCD subtype diffuse large B-cell lymphoma (DLBCL). The primary endpoint is the 2-year progression-free survival (PFS) rate; secondary endpoints include overall response rate (ORR), complete response rate (CRR), overall survival (OS), and treatment-related adverse events (TRAEs). The study plans to enroll 66 patients.

Conditions

DLBCL - Diffuse Large B Cell Lymphoma

Keywords

orelabrutinib; DLBCL; chemotherapy; Maintenance therapy; MCD subtype

Outcome Measures

Primary Outcomes (1)

• 2year PFS

  The percentage of subjects who had not experienced disease progression or all-cause death at 24 months from first dose, relative to the total enrolled population.

  From the start of treatment up to 2 years

Secondary Outcomes (4)

• ORR

  From the start of treatment up to 2 years

• CRR

  From the start of treatment up to 2 years

• OS

  From the start of treatment up to 2 years

• AEs

  From the start of treatment up to 2 years

Study Arms (1)

Orelabrutinib Combined with chemotherapy followed by monotherapy in ND MCD subtype DLBCL

EXPERIMENTAL

For MCD subtype DLBCL (including IP-LBCLs) that have undergone two cycles of induction therapy, combine orelabrutinib treatment starting from the third cycle. For patients with poor prognostic factors (meeting one of the following: Ann Arbor stage III/IV; IPI score 3-5; aaIPI score 2-3; high-intermediate or high-risk group per MSKCC and/or IELSG criteria), continue with two additional cycles of orelabrutinib-combined induction therapy, followed by orelabrutinib monotherapy maintenance for 2 years or until disease progression or intolerable toxicity. For patients without poor prognostic factors, administer orelabrutinib monotherapy maintenance for 1 year or until disease progression or intolerable toxicity.

Drug: R-CHOP+Orelabrutinib; Drug: POLA-R-CHP+orelabrutinib; Drug: R-miniCHOP +orelabrutinib; Drug: Zuberitamab-CHOP+orelabrutinib; Drug: POLA-Hi-CHP+orelabrutinib; Drug: Hi-miniCHOP +orelabrutinib; Drug: RMTO; Drug: HiMTO; Drug: Pola-R-miniCHP+O; Drug: Pola-Hi-miniCHP

Interventions

R-CHOP+Orelabrutinib DRUG

R-CHOP Regimen Rituximab: 375 mg/m², Day 0 Cyclophosphamide: 750 mg/m², Day 1 Doxorubicin: 50 mg/m², Day 1 Vincristine: 1.4 mg/m², Day 1 (maximum single dose: 2 mg) Prednisone: 100 mg, Days 1-5 Orelabrutinib 150mg QD every 21 days per cycle in Induction therapy, 28 days/cycle during maintenance therapy

Also known as: Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, Orelabrutinib

Orelabrutinib Combined with chemotherapy followed by monotherapy in ND MCD subtype DLBCL

POLA-R-CHP+orelabrutinib DRUG

POLA-R-CHP+orelabrutinib Rituximab: 375 mg/m², Day 1 Vepoliximab: 1.8 mg/kg, Day 1 Cyclophosphamide: 750 mg/m², Day 1 Doxorubicin: 50 mg/m², Day 1 Prednisone: 100 mg, Days 1-5 orelabrutinib 150mg QD every 21 days per cycle in Induction therapy, 28 days/cycle during maintenance therapy

Also known as: Rituximab, Vepoliximab, Cyclophosphamide, Doxorubicin, Prednisone, orelabrutinib

Orelabrutinib Combined with chemotherapy followed by monotherapy in ND MCD subtype DLBCL

R-miniCHOP +orelabrutinib DRUG

R-miniCHOP Regimen Rituximab: 375 mg/m², Day 0 Cyclophosphamide: 400 mg/m², Day 1 Doxorubicin: 25 mg/m², Day 1 Vincristine: 1 mg, Day 1 Prednisone: 40 mg/m², Days 1-5 orelabrutinib 150mg QD every 21 days per cycle in Induction therapy, 28 days/cycle during maintenance therapy

Also known as: Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, orelabrutinib

Orelabrutinib Combined with chemotherapy followed by monotherapy in ND MCD subtype DLBCL

Zuberitamab-CHOP+orelabrutinib DRUG

Zuberitamab: 375 mg/m², Day 0 Cyclophosphamide: 400 mg/m², Day 1 Doxorubicin: 25 mg/m², Day 1 Vincristine: 1 mg, Day 1 Prednisone: 40 mg/m², Days 1-5 orelabrutinib 150mg QD every 21 days per cycle in Induction therapy, 28 days/cycle during maintenance therapy

Also known as: Zuberitamab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone

Orelabrutinib Combined with chemotherapy followed by monotherapy in ND MCD subtype DLBCL

POLA-Hi-CHP+orelabrutinib DRUG

POLA-Hi-CHP+orelabrutinib Zuberitamab: 375 mg/m², Day 1 Vepoliximab: 1.8 mg/kg, Day 1 Cyclophosphamide: 750 mg/m², Day 1 Doxorubicin: 50 mg/m², Day 1 Prednisone: 100 mg, Days 1-5 orelabrutinib 150mg QD every 21 days per cycle in Induction therapy, 28 days/cycle during maintenance therapy

Also known as: Vepoliximab, Cyclophosphamide, Doxorubicin, Prednisone, orelabrutinib, Zuberitamab

Orelabrutinib Combined with chemotherapy followed by monotherapy in ND MCD subtype DLBCL

Hi-miniCHOP +orelabrutinib DRUG

Hi-miniCHOP Regimen Zuberitamab: 375 mg/m², Day 0 Cyclophosphamide: 400 mg/m², Day 1 Doxorubicin: 25 mg/m², Day 1 Vincristine: 1 mg, Day 1 Prednisone: 40 mg/m², Days 1-5 orelabrutinib 150mg QD every 21 days per cycle in Induction therapy, 28 days/cycle during maintenance therapy

Also known as: Zuberitamab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone,, orelabrutinib

Orelabrutinib Combined with chemotherapy followed by monotherapy in ND MCD subtype DLBCL

RMTO DRUG

RMTO Regimen Rituximab: 375 mg/m², Day 1 Methotrexate: 3.5 g/m², Day 2 Thiotepa 30 mg/m² Day 4 Orelabrutinib: 150 mg, Days 1-21 every 21 days per cycle in Induction therapy, maintenance therapy 28 days/cycle

Also known as: Rituximab, orelabrutinib, Thiotepa, Methotrexate

Orelabrutinib Combined with chemotherapy followed by monotherapy in ND MCD subtype DLBCL

HiMTO DRUG

HiMTO Regimen Zuberitamab: 375 mg/m², Day 1 Methotrexate: 3.5 g/m², Day 2 Thiotepa 30 mg/m² Day 4 Orelabrutinib: 150 mg, Days 1-21 every 21 days per cycle in Induction therapy, maintenance therapy 28 days/cycle

Also known as: Zuberitamab, orelabrutinib, Thiotepa, Methotrexate

Orelabrutinib Combined with chemotherapy followed by monotherapy in ND MCD subtype DLBCL

Pola-R-miniCHP+O DRUG

Pola-R-miniCHP Regimen Polatuzumab vedotin: 1.8 mg/kg IV, Day 1 Rituximab: 375 mg/m² IV, Day 1 Cyclophosphamide: 400 mg/m² IV, Day 1 Doxorubicin: 25 mg/m² IV, Day 1 Prednisone: 40 mg/m² PO, Days 1-5 every 21 days per cycle in Induction therapy, maintenance therapy 28 days/cycle

Also known as: Polatuzumab vedotin, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone

Orelabrutinib Combined with chemotherapy followed by monotherapy in ND MCD subtype DLBCL

Pola-Hi-miniCHP DRUG

Pola-Hi-miniCHP Regimen (21-day cycle, up to 6 cycles) Polatuzumab vedotin: 1.8 mg/kg IV, Day 1 Zuberitamab: 375 mg/m² IV, Day 1 Cyclophosphamide: 400 mg/m² IV, Day 1 Doxorubicin: 25 mg/m² IV, Day 1 Prednisone: 40 mg/m² PO, Days 1-5 every 21 days per cycle in Induction therapy, maintenance therapy 28 days/cycle

Also known as: Polatuzumab vedotin, Cyclophosphamide, Doxorubicin, Prednisone, Zuberitamab, orelabrutinib

Orelabrutinib Combined with chemotherapy followed by monotherapy in ND MCD subtype DLBCL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of any gender, aged ≥18 years;
• Pathologically, NGS, and imaging confirmed diagnosis of MCD subtype DLBCL (including IP-LBCLs);
• No prior treatment history;
• Serum creatinine ≤2 times the upper limit of normal or eGFR ≥40 ml/min;
• Bilirubin \<1.5 times the upper limit of normal;
• Understand and voluntarily sign a written informed consent form.

You may not qualify if:

• Pregnant or lactating women and women of childbearing age who are unwilling to use contraception;
• Patients with a history of stroke or bleeding within the past 6 months;
• Patients requiring treatment with strong CYP3A inhibitors;
• Patients with comorbid autoimmune deficiency diseases or active hepatitis virus infection;
• Patients with a history of organ transplantation;
• Patients with a history of or concurrent other malignant tumors.

Sponsors & Collaborators

• Ou Bai, MD/PHD: lead

Study Sites (1)

The First Bethune Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; orelabrutinib; Thiotepa; Methotrexate; polatuzumab vedotin

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Aminopterin; Pterins; Pteridines

Central Study Contacts

ou bai, MD/PHD

CONTACT

13039046656; oubai16@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Professor

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: July 1, 2026
• Study Start: June 16, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2031
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)