Anti-PD-1 Antibody Alone or in Combination With Decitabine/Chemotherapy in Relapsed or Refractory Malignancies

Han weidong

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Malignancies Multiple

Treatments: Drug: Chemotherapy; Drug: Anti-PD-1 antibody; Drug: Decitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT02961101

CHN-PLAGH-BT-019

Details and patient eligibility

About

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.

Full 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.

Enrollment: 250 estimated patients

Sex: All

Ages: 12 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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250 participants in 3 patient groups

Anti-PD-1 antibody+decitabine

Experimental group

Description:

Decitabine will be administrated at 10mg/d on day1 to 5, followed by Anti-PD-1 antibody 200mg on day8 IV Q3 weeks until progression.

Treatment:

Drug: Decitabine

Drug: Anti-PD-1 antibody

Anti-PD-1 antibody

Experimental group

Description:

Anti-PD-1 antibody 200mg IV Q3 weeks until progression.

Treatment:

Drug: Anti-PD-1 antibody

Anti-PD-1 antibody+chemotherapy

Experimental group

Description:

Chemotherapy will be given depends on the cancer type and treatment regimen before enrollment. Chemotherapy was administrated on day1 , followed by Anti-PD-1 antibody 200mg on day2 IV Q3 weeks until progression. Following disease remission, radiotherapy could be administered or omitted for consolidation at the discretion of the investigator.

Treatment:

Drug: Anti-PD-1 antibody

Drug: Chemotherapy