HDM2005 Combination Therapy in Relapsed/Refractory Mantle Cell Lymphoma

July 9, 2026 updated by: Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

A Phase Ib/III Clinical Trial to Evaluate HDM2005 in Combination Therapy for Patients With Relapsed/Refractory Mantle Cell Lymphoma

This is a Phase Ib/III, multicenter, open-label clinical study of HDM2005 in combination with rituximab and lenalidomide in adult patients with relapsed or refractory mantle cell lymphoma.

Mantle cell lymphoma is a type of non-Hodgkin lymphoma. Some patients have disease that comes back after treatment or does not respond well to available treatments. This study is designed to evaluate whether adding HDM2005 to rituximab and lenalidomide may provide clinical benefit for patients with relapsed or refractory mantle cell lymphoma who have previously received an anti-CD20 antibody-containing regimen and at least one Bruton's tyrosine kinase inhibitor.

The study includes two parts. In the Phase Ib part, participants will receive HDM2005 in combination with rituximab and lenalidomide. The main goals of this part are to evaluate the safety and tolerability of the combination, assess preliminary anti-tumor activity, and determine the recommended dose of HDM2005 for the Phase III part.

In the Phase III part, eligible participants will be randomly assigned to receive either HDM2005 at the recommended Phase III dose in combination with rituximab and lenalidomide, or the investigator's choice of comparator treatment with rituximab plus lenalidomide or bendamustine plus rituximab. The main goals of the Phase III part are to compare the anti-tumor activity and clinical benefit of the HDM2005 combination with the comparator treatments. The main measures of efficacy include objective response rate and progression-free survival, assessed according to the 2014 Lugano response criteria. The study will also evaluate safety, pharmacokinetics, immunogenicity, overall survival, duration of response, and other measures of anti-tumor activity.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adult participants aged 18 years or older.
  2. Histologically confirmed mantle cell lymphoma with cyclin D1 overexpression or documented t(11;14).
  3. Relapsed or refractory mantle cell lymphoma after prior treatment with an anti-CD20 antibody-containing regimen and at least one Bruton's tyrosine kinase inhibitor, unless a BTK inhibitor was not suitable or was not tolerated.
  4. At least one measurable lesion according to the 2014 Lugano response criteria.
  5. Eastern Cooperative Oncology Group performance status of 0 to 1 for the Phase Ib part, or 0 to 2 for the Phase III part.
  6. Adequate organ and bone marrow function as defined in the protocol.
  7. Estimated life expectancy of more than 3 months.
  8. Willingness to provide archived or fresh tumor tissue for central pathology review, if available.
  9. Willingness to follow the study treatment plan, visit schedule, and contraceptive requirements.
  10. Written informed consent provided before any study-specific procedures.

Exclusion Criteria:

  1. Leukemic non-nodal mantle cell lymphoma.
  2. Known central nervous system involvement by lymphoma.
  3. Prior treatment with a ROR1-targeted therapy.
  4. Active or uncontrolled infection requiring systemic treatment.
  5. Active infectious disease, including uncontrolled hepatitis B, active hepatitis C, human immunodeficiency virus infection, or active syphilis, as defined in the protocol.
  6. History or current evidence of interstitial lung disease, active interstitial lung disease, or radiation pneumonitis requiring steroid treatment.
  7. Clinically significant cardiovascular or cerebrovascular disease that may increase study risk.
  8. Prior allogeneic hematopoietic stem cell transplantation with active or clinically significant graft-versus-host disease, or need for systemic immunosuppressive treatment for graft-versus-host disease.
  9. Prior solid organ transplantation.
  10. Other active malignancy or malignancy with a clinically significant risk of recurrence, except for certain adequately treated cancers as defined in the protocol.
  11. Unresolved clinically significant toxicity from prior anti-cancer therapy.
  12. Recent anti-cancer therapy, investigational treatment, major surgery, or radiotherapy within the protocol-defined washout period.
  13. Known allergy or contraindication to any study treatment or its components.
  14. Active autoimmune disease or immunodeficiency requiring systemic treatment, except for protocol-defined stable conditions.
  15. Pregnancy, breastfeeding, or planned pregnancy during the study.
  16. Any medical, psychiatric, laboratory, or social condition that, in the investigator's judgment, may interfere with study participation, study assessments, or participant safety.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase Ib Cohort 1: HDM2005 1.2 mg/kg + R-Len
Participants in this Phase Ib cohort will receive HDM2005 1.2 mg/kg in combination with rituximab and lenalidomide during induction treatment.
Drug: Phase Ib Cohort 1: HDM2005 1.2 mg/kg + R-Len
HDM2005 will be administered in combination with rituximab and lenalidomide.
Other Names:
  • HDM2005 + R-Len
Experimental: Phase Ib Cohort 2: HDM2005 1.4 mg/kg + R-Len
Participants in this Phase Ib cohort will receive HDM2005 1.4 mg/kg in combination with rituximab and lenalidomide during induction treatment.
Drug: Phase Ib Cohort 2: HDM2005 1.4 mg/kg + R-Len
HDM2005 will be administered in combination with rituximab and lenalidomide.
Other Names:
  • HDM2005 + R-Len
Experimental: Phase III Active Arm: HDM2005 plus rituximab and lenalidomide
HDM2005 will be administered in combination with rituximab and lenalidomide.
Drug: HDM2005 plus rituximab and lenalidomide
HDM2005 will be administered in combination with rituximab and lenalidomide.
Other Names:
  • HDM2005 + R-Len
Active Comparator: Phase III Control Arm: Rituximab plus lenalidomide
Rituximab plus lenalidomide is used as part of the HDM2005 combination regimen as control arm.
Drug: Rituximab plus lenalidomide
Rituximab plus lenalidomide is used as part of the HDM2005 combination regimen and may also be selected as comparator treatment in the Phase III part.
Other Names:
  • R-Len

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase Ib: Incidence and severity of adverse events
Time Frame: From the date of first dose until end of treatment, assessed up to 12 months.
Incidence and severity of adverse events, serious adverse events, and adverse events of special interest will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Dose interruptions, dose modifications, laboratory test results, vital signs, and other safety assessments will also be evaluated.
From the date of first dose until end of treatment, assessed up to 12 months.
Phase Ib: Objective response rate assessed by investigator
Time Frame: From the first dose of study treatment until disease progression, or other protocol re-specified reasesons, whichever occurs first, assessed up to 11 months.
Objective response rate is defined as the proportion of participants who achieve complete response or partial response as assessed by the investigator according to the 2014 Lugano response criteria.
From the first dose of study treatment until disease progression, or other protocol re-specified reasesons, whichever occurs first, assessed up to 11 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 10, 2026

Primary Completion (Estimated)

August 10, 2027

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

July 2, 2026

First Submitted That Met QC Criteria

July 9, 2026

First Posted (Actual)

July 13, 2026

Study Record Updates

Last Update Posted (Actual)

July 13, 2026

Last Update Submitted That Met QC Criteria

July 9, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HDM2005-301

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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