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

Sponsor
First Affiliated Hospital of Zhejiang University
Study ID
NCT07159906
Phase
PHASE1/PHASE2
Status
Not Yet Recruiting

Notify me when recruiting opens

Save your spot on the interest list for this study. We'll keep your details with this study so our team can follow up when recruiting opens.

Not yet recruiting

Add your contact details and location so we can keep your interest tied to this study.

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 99 Years
Healthy Volunteers
Not accepted

Interventions

  • Homoharringtonine — DRUG
    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).
  • BCL-2 inhibitor — DRUG
    An oral selective BCL2 inhibitor administered once daily D1-7. Combined with homoharringtonine, rituximab, and prednisone in 21-day cycles.
  • CD20 Antibody — DRUG
    An anti-CD20 monoclonal antibody administered intravenously, used in combination with chemotherapy or targeted regimens for B-cell malignancies.
  • Glucocorticoid (GC) — DRUG
    glucocorticoid , given as part of the combination regimen to enhance anti-lymphoma effect.

Study Details

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.

Key Dates

First listed
Sep 8, 2025
Start date
Sep 8, 2025
Status verified
Aug 2025
Primary completion
Aug 1, 2027
Completion
Aug 1, 2028

Study Design

Enrollment
62 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: HHT-Based Combination
    Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will receive the investigational combination of homoharringtonine, BCL2 inhibitor, rituximab, and prednisone. Treatment will be administered in 21-day cycles, with dose escalation in Phase Ib to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase II dose (RP2D), followed by a Phase II expansion to evaluate efficacy and safety.

Primary Outcome Measure

Dose-Limiting Toxicities (DLT) [ Time Frame: Cycle 1 (first 21-day cycle) ]

Central Contacts

Related Studies