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

Malignancies Multiple Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02961101
• Other study ID #: CHN-PLAGH-BT-019
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 2016
• Est. completion date: May 2020

Study information

• Verified date: July 2019
• Source: Chinese PLA General Hospital
• Contact: Weidong Han, doctor
• Phone: +86-010-66937463
• Email: hanwdrsw[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: May 2020
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Malignancies Multiple
• Neoplasms

Intervention

Drug:
• Anti-PD-1 antibody
Anti-PD-1 antibody will be given at 1-3mg/kg on day8 by IV every three weeks
• Decitabine
Decitabine will be given at 10mg/d on day 1to 5 by IV every three weeks
• Chemotherapy
Chemotherapy be given depends on the cancer type and treatment regimen before enrollment.

Locations

Country	Name	City	State
China	Biotherapeutic Department of Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Han weidong

Country where clinical trial is conducted

China, 

References & Publications (2)

Mei Q, Chen M, Lu X, Li X, Duan F, Wang M, Luo G, Han W. An open-label, single-arm, phase I/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma. Oncotarget. 2015 Jun 30;6(18):16698-711. — View Citation

Nie J, Zhang Y, Li X, Chen M, Liu C, Han W. DNA demethylating agent decitabine broadens the peripheral T cell receptor repertoire. Oncotarget. 2016 Jun 21;7(25):37882-37892. doi: 10.18632/oncotarget.9352. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.		2 years
Secondary	Objective response by Response Evaluation Criteria in Solid Tumors (RECIST1.1).		3 years
Secondary	Objective response by the International Workshop to Standardize Response Criteria for lymphomas.		3 years
Secondary	Progression free survival		3 years
Secondary	Overall survival		3 years