Clinical trial NCT02961101: Anti-PD-1 Antibody Alone or in Combination With Decitabine/Chemotherapy in Relapsed or Refractory Malignancies
Official title: Anti-PD-1 Antibody Alone or in Combination With Low-dose Decitabine and/or Chemotherapy in Relapsed or Refractory Malignancies: an Open-label Phase I/II Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Malignancies Multiple
Keywords: relapsed or refractory
malignancies
decitabine
anti-PD-1 antibody
chemotherapy
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2016-11-10
Enrollment: 250
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the feasibility, safety, and efficacy of anti-PD-1 antibody alone or in combination with low-dose decitabine in patients with relapsed or refractory malignancies, including Non-Hodgkin'lymphoma, Hodgkin'lymphoma, gastrointestinal cancers, hepatocellular carcinoma, breast cancer, ovarian cancer or lung cancer or renal-cell cancer or pancreatic cancer or bile duct cancer.

Detailed description: Primary objective: To assess the feasibility and safety for Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy administered every 3 weeks to subjects with relapsed or refractory malignancies.

Secondary objectives: 1) To assess the antitumor activity of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy in subjects with relapsed or refractory malignancies. 2) To characterize the immunological effects of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy. 3) To characterize the immunological effects of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy.

Exploratory objectives: 1) To analysis of potential biological parameters correlated to clinical response and toxicities. 2) To search predictive biomarkers to guide the choose of patients undergoing the treatment of Anti-PD-1 antibody alone or in combination with decitabine and/or chemotherapy.

Safety Evaluation: Adverse events will be assessed continuously during the study and for 100 days post last treatment, and will be evaluated according to the NCI CTCAE Version 4.0.

Efficacy Evaluation: 1) Treatment response to lymphoma was defined using the International Workshop to Standardize Response Criteria for Lymphomas; 2) Treatment response to solid tumors was defined using Response Evaluation Criteria in Solid Tumors (RECIST1.1).

evaluation index: BOR; ORR; PFS and OS.

Eligibility criteria: Inclusion Criteria:

1. Subjects must have histological confirmation of relapsed or refractory malignancies,including Non-Hodgkin'lymphoma, Hodgkin'lymphoma, gastrointestinal cancers, hepatocellular carcinoma, breast cancer, ovarian cancer or lung cancer or renal-cell cancer or pancreatic cancer or bile duct cancer.
2. 12 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 \>1 cm as defined by lymphoma response criteria; with solid tumors must have at least one measureable lesion \>1 cm per RECIST1.1.
6. Subjects must have received at least two prior chemotherapy regimen, 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 bone marrow, live, renal, lung and heart functions.

   1. Absolute neutrophil count greater than or equal to 1,000/μL.
   2. Platelet count greater than or equal to 70,000/µL.
   3. Serum bilirubin level less than or equal to 1.5 x upper limits of normal (ULN).
   4. Serum creatinine less than or equal to 1.5 x ULN.
   5. Alanine aminotransferase \[ALT or SGPT\] and aspartate aminotransferase \[AST or SGOT\] less than or equal to 2.5 x ULN.

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 and intestinal 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. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
timeFrame: 2 years
Secondary outcomes:
measure: Objective response by Response Evaluation Criteria in Solid Tumors (RECIST1.1).
timeFrame: 3 years
measure: Objective response by the International Workshop to Standardize Response Criteria for lymphomas.
timeFrame: 3 years
measure: Progression free survival
timeFrame: 3 years
measure: Overall survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Biotherapeutic Department of Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853
name: Chunmeng Wang, Master
role: STUDY_DIRECTOR
affiliation: Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853
name: Wenying Zhang, Master
role: STUDY_DIRECTOR
affiliation: Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853
name: Yang Liu, Doctor
role: STUDY_DIRECTOR
affiliation: Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853
name: Meixia Chen, Doctor
role: STUDY_DIRECTOR
affiliation: Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853
name: Yan Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
name: Qian Mei, Doctor
role: STUDY_DIRECTOR
affiliation: Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
name: Jing Nie, Doctor
role: STUDY_DIRECTOR
affiliation: Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
name: Xiang Li, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
name: Liang Dong, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Molecular Biology, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
name: Lu Shi, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853
name: Kaichao Feng, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853
name: Jingdan Qiu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Biotherapeutic Department of Chinese PLA General Hospital, Beijing, China, 100853
name: Hejin Jia, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Wang C, Liu Y, Dong L, Li X, Yang Q, Brock MV, Mei Q, Liu J, Chen M, Shi F, Liu M, Nie J, Han W. Efficacy of Decitabine plus Anti-PD-1 Camrelizumab in Patients with Hodgkin Lymphoma Who Progressed or Relapsed after PD-1 Blockade Monotherapy. Clin Cancer Res. 2021 May 15;27(10):2782-2791. doi: 10.1158/1078-0432.CCR-21-0133. Epub 2021 Mar 5.
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