Overview
The issue of therapy after PD-1 inhibitor failure is unresolved in classic Hodgkin lymphoma. Preliminary clinical observations have shown that patients might benefit from Chidamide+Decitabine plus anti-PD-1 antibody. This open-label, randomized, phase 2 study aims to evaluate the efficacy of Chidamide+Decitabine plus anti-PD-1 and the standard of care, which includes anti-PD-1 antibody, in patients with classical Hodgkin lymphoma who have experienced failure with PD-1 inhibitor. The primary objective of the study is to evaluate the 12-month progression-free survival rates.
Description
Anti-PD-1 antibody induces a high response rate in patients with relapsed/refractory classic Hodgkin lymphoma, but more than 60% of patients have disease relapse or progression during or after immune checkpoint inhibitors and subsequent salvage therapies could not meet the need. Preliminary clinical observations have shown that Chidamide+Decitabine plus anti-PD-1 antibody might be beneficial for these patients.
This open-label, randomized, phase 2 study aims to evaluate the efficacy of Chidamide+Decitabine plus anti-PD-1 antibody and the standard of care, which includes anti-PD-1 antibody, in patients with classical Hodgkin lymphoma who have experienced failure with PD-1 inhibitor. The standard of care involves Gemcitabine, Vinorelbine, and Pegylated liposomal doxorubicin (GVD) or Ifosfamide, Carboplatin, and Etoposide (ICE) or Brentuximab Vedotin (BV) plus PD-1 inhibitor. The specific regimen will be determined by investigators.
The primary objective of the study is to evaluate the 12-month progression-free survival rates. The key secondary end points are complete response rate, objective response rate and the safety.
Eligibility
Inclusion Criteria:
1.Subjects must have histological confirmation classical Hodgkin lymphoma (cHL).
2.18 to 75 years of age.
3.ECOG performance of less than 2.
4.Life expectancy of at least 3 months.
5.Subjects with lymphoma must have at least one measureable lesion >1cm as defined by
lymphoma response criteria.
6.Subjects must have received Anti-PD-1 antibody therapy and were confirmed Anti-PD-1
antibody failure, and must be off therapy for at least 4 weeks prior to Day 1. Subjects
with autologous hematopoietic stem-cell transplantation are eligible which must be more
than 3 months.
7.Subjects must have adequate marrow, live, renal and heart functions.
8.Patients who have received Chidamide+Decitabine+ immune checkpoint inhibitors can be
directly assigned to the control group without randomization.
Exclusion Criteria:
1. Subjects with any autoimmune disease or history of syndrome that requires
corticosteroids or immunosuppressive medications.
2. Serious uncontrolled medical disorders or active infections, pulmonary infection
especially.
3. Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1
month.
4. Prior organ allograft.
5. Women who are pregnant or breastfeeding.
6. Women with a positive pregnancy test on enrollment or prior to investigational product
administration.
7. Subjects who are compulsorily detained for treatment of either a psychiatric or
physical illness.
8. The experimental group have received the combination therapy of Chidamide, Decitabine
and anti-PD-1 antibody and the standard of care group have received all the three
therapy of GVD+ anti-PD-1 antibody, ICE + anti-PD-1 antibody and BV+ anti-PD-1
antibody.