HDM2005 Combination Therapy in Relapsed/Refractory Mantle Cell Lymphoma

Official title

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

Overview

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.

Interventions

• Drug Phase Ib Cohort 1: HDM2005 1.2 mg/kg + R-Len
  HDM2005 will be administered in combination with rituximab and lenalidomide.
• 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.
• Drug Phase Ib Cohort 2: HDM2005 1.4 mg/kg + R-Len
  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.

Primary outcome measures

• 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.]
• 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.]

Eligibility criteria

Inclusion criteria

• Adult participants aged 18 years or older.
• Histologically confirmed mantle cell lymphoma with cyclin D1 overexpression or documented t(11;14).
• 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.
• At least one measurable lesion according to the 2014 Lugano response criteria.
• Eastern Cooperative Oncology Group performance status of 0 to 1 for the Phase Ib part, or 0 to 2 for the Phase III part.
• Adequate organ and bone marrow function as defined in the protocol.
• Estimated life expectancy of more than 3 months.
• Willingness to provide archived or fresh tumor tissue for central pathology review, if available.
• Willingness to follow the study treatment plan, visit schedule, and contraceptive requirements.
• Written informed consent provided before any study-specific procedures.

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07697339 · HDM2005-301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗