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

Chinese PLA General Hospital (301 Hospital)

Status and phase: Not yet enrolling; Phase 2

Conditions: Ineligible Or Refused Transplant Patients With Classical Hodgkin Lymphoma

Treatments: Drug: Chidamide; Decitabine; Anti-PD-1 Antibody; Drug: Brentuximab Vedotin+ Bendamustine+Anti-PD-1 antibody

Study type: Interventional

Funder types: Other

Identifiers

NCT06563778

CHN-PLAGH-BT-089

Details and patient eligibility

About

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.

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Chidamide+Decitabine+ Anti-PD-1 Antibody

Experimental group

Description:

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.

Treatment:

Drug: Chidamide; Decitabine; Anti-PD-1 Antibody

Brentuximab Vedotin+ Bendamustine+anti-PD-1 antibody

Active Comparator group

Treatment:

Drug: Brentuximab Vedotin+ Bendamustine+Anti-PD-1 antibody