MedTrace Logo

Homoharringtonine, BCL-2 Inhibitor, Rituximab, and Prednisone in Relapsed/Refractory Diffuse Large B-Cell Lymphoma

NCT07159906 · Status: NOT_YET_RECRUITING · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 62

Last updated 2025-09-08

No results posted yet for this study

Summary

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in China and worldwide. Although standard immunochemotherapy with Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine (Oncovin), and Prednisone (R-CHOP) achieves durable remissions in many patients, approximately 30-40% experience relapse or refractory disease with poor outcomes. Novel strategies are needed for patients who are not candidates for transplantation or who relapse after multiple lines of therapy.

Homoharringtonine (HHT) is a natural cephalotaxine alkaloid extracted from Cephalotaxus species, clinically approved in China for acute and chronic myeloid leukemias. It inhibits ribosomal protein synthesis, modulates oncogenic and epigenetic signaling pathways, and induces apoptosis through mitochondrial and stress-activated pathways. Importantly, HHT downregulates the anti-apoptotic protein Myeloid Cell Leukemia 1 (MCL-1), a critical resistance factor to B-cell lymphoma 2 (BCL-2) inhibitors. This provides a strong mechanistic rationale for combining HHT with a BCL-2 inhibitor, together with rituximab and prednisone, in relapsed/refractory DLBCL.

This prospective, multicenter, single-arm, Phase Ib/II study will evaluate the safety, tolerability, and efficacy of HHT, a BCL-2 inhibitor, rituximab, and prednisone in adult patients with relapsed/refractory DLBCL. Phase Ib will enroll 15-22 patients to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and the recommended phase II dose (RP2D) of HHT. Phase II will enroll 40 patients treated at RP2D to evaluate the overall response rate (ORR) after 3 and 6 cycles per Lugano 2014 criteria. Secondary endpoints include complete remission (CR), partial remission (PR), progression-free survival (PFS), and overall survival (OS). Exploratory analyses will incorporate molecular biomarkers such as genomic profiling, circulating tumor DNA (ctDNA), and spatial transcriptomics.

Conditions

  • Diffuse Large B-Cell Lymphoma
  • Relapsed Non-Hodgkin Lymphoma
  • Refractory Non-Hodgkin Lymphoma

Interventions

DRUG

Homoharringtonine

A cephalotaxine alkaloid and protein synthesis inhibitor that downregulates Myeloid Cell Leukemia 1 (MCL-1), administered intravenously in 21-day cycles. Dose escalation in Phase Ib will determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase II dose (RP2D).

DRUG

BCL-2 inhibitor

An oral selective BCL2 inhibitor administered once daily D1-7. Combined with homoharringtonine, rituximab, and prednisone in 21-day cycles.

DRUG

CD20 Antibody

An anti-CD20 monoclonal antibody administered intravenously, used in combination with chemotherapy or targeted regimens for B-cell malignancies.

DRUG

Glucocorticoid (GC)

glucocorticoid , given as part of the combination regimen to enhance anti-lymphoma effect.

Sponsors & Collaborators

  • First Affiliated Hospital of Zhejiang University

    lead OTHER

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
99 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2025-09-08
Primary Completion
2027-08-01
Completion
2028-08-01

Countries

  • China

Study Locations

More Related Trials

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07159906 on ClinicalTrials.gov