Chidamide+Decitabine Plus Anti-PD-1 Antibody for Patients With R/R cHL Who Are Transplant-ineligible or Refused Transplant.

A Randomized, Open-label, Phase 2 Trial of Chidamide+Decitabine Plus Anti-PD-1 Antibody for Patients With R/R cHL Who Are Transplant-ineligible or Refused Transplant

The prognosis for patients with relapsed/refractory classical Hodgkin lymphoma (cHL) who refuse or are ineligible for transplant is poor. This open label, randomized, phase 2 study aims to evaluate the efficacy of Chidamide+Decitabine plus Anti-PD-1 Antibody and Brentuximab Vedotin + Bendamustine plus Anti-PD-1 Antibody in transplant-ineligible or refused transplant diagnosed R/R cHL. The primary objective of the study is to evaluate progression-free survival.

Study Overview

• Status: Not yet recruiting
• Conditions: Ineligible Or Refused Transplant Patients With Classical Hodgkin Lymphoma
• Intervention / Treatment: Drug: Chidamide; Decitabine; Anti-PD-1 Antibody; Drug: Brentuximab Vedotin+ Bendamustine+Anti-PD-1 antibody

Detailed Description

The prognosis of refractory or early-relapsed lymphoma is poor, and it is even worse for those who are not eligible or refuse transplantation. Although many salvage regimens have been developed, there is no standard of care. Preliminary clinical observations have shown that Chidamide +Decitabine plus Anti-PD-1 Antibody might be beneficial for these patients. Brentuximab Vedotin or Bendamustine plus Anti-PD-1 Antibody are both standard regimens.The combination of Brentuximab Vedotin, Bendamustine and Anti-PD-1 Antibody may be another effective regimen. This open-label, randomized, phase 2 study aims to evaluate the efficacy of Chidamide+Decitabine plus anti-PD-1 antibody and Brentuximab Vedotin + Bendamustine plus Anti-PD-1 Antibody, in patients with classical Hodgkin lymphoma who are transplant-ineligible or refused transplant .

The primary objective of the study is to evaluate the progression free survival. The key secondary end points are complete response rate, objective response rate and the safety.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Han W dong, Prfessor; Phone Number: 01055499341; Email: hanwdrsw@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital
      • Contact: Han W Weidong, Prfessor; Phone Number: 86-10-13651392893; Email: hanwdrsw@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: 1.18 to 75 years of age. 2.ECOG performance of less than 2. 3.Subjects must have histological confirmation classical Hodgkin lymphoma (cHL). 4. Patients must have at least two lines of antitumor therapy, those who were transplant-ineligible or refused transplant. 5.Life expectancy of at least 3 months. 6.Subjects with lymphoma must have at least one measureable lesion >1cm as defined by lymphoma response criteria. 7. Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to ≤ grade 1 toxicity. 8.Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months. 9.Subjects must have adequate marrow, live, renal and heart functions.

-

Exclusion Criteria:1. Subjects have received the combination therapy of Chidamide+Decitabine and anti-PD-1 antibody or Brentuximab Vedotin + Bendamustine Plus Anti-PD-1 Antibody. 2.Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications. 3. Serious uncontrolled medical disorders or active infections, pulmonary infection especially. 4. Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1 month. 5. Prior organ allograft. 6. Women who are pregnant or breastfeeding. 7. Women with a positive pregnancy test on enrollment or prior to investigational product administration. 8. Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.

-

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chidamide+Decitabine+ Anti-PD-1 Antibody; Chidamide is a novel and orally active benzamide class of HDAC inhibitor that selectively inhibits activity of HDAC1, 2, 3 and 10, which can Induce tumor-cell apoptosis, suppress cell proliferation and enhance immune surveillance. Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1(DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function. Immune checkpoint inhibitors have emerged as effective therapies for many cancers by promoting the reactivation and restoring function of T cells.	Drug: Chidamide; Decitabine; Anti-PD-1 Antibody; Chidamide 10mg/day, day1-4; 20mg/day, day 8,11, 15, 18. Decitabine 10mg/day, day1-5. Physicians will decide which immune checkpoint inhibitors will be used during treatment.
Active Comparator: Brentuximab Vedotin+ Bendamustine+anti-PD-1 antibody	Drug: Brentuximab Vedotin+ Bendamustine+Anti-PD-1 antibody; Brentuximab Vedotin 1.2-1.8mg/kg day 1, Bendamustine 70-90mg/m2 day1-2, Anti-PD-1 antibody day 2. Physicians will decide which immune checkpoint inhibitors will be used during treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Time from the date of first administration of the study drug to disease progression or death from any cause (any earliest date).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate (CRR)	CRR assess by investigators per the 2014 Lugano classification rate of subjects achieved complete response in all evaluable subjects	1 year
Objective response rate (ORR)	The percentage of patients with CR or PR was determined according to the revised lymphoma efficacy evaluation criteria (Lugano 2014 criteria).	1 year
Number of Subjects with treatment-related adverse events (AEs)	Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers predictive of efficacy and toxicity	Biomarkers such as PD-1 from tumor tissue and peripheral blood will be assessed for their potential in predicting clinical efficacy and toxicity.	1 year

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: August 19, 2024
• First Submitted That Met QC Criteria: August 19, 2024
• First Posted (Actual): August 21, 2024

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Immunoconjugates; Immunotoxins; Decitabine; Antibodies; Immunoglobulins; Bendamustine Hydrochloride; Brentuximab Vedotin
• Other Study ID Numbers: CHN-PLAGH-BT-089

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No