A Safety Study of the Pan-immunotherapy in Patients With Unresectable/Metastatic Solid Tumors or Lymphomas

Lymphoma Clinical Trial

Official title:

A Phase I, Two-arm, Open-label, Single-center, Dose-escalation Study to Evaluate the Safety, Tolerability and Recommended Dose and Delivery Mode of the Pan-immunotherapy in Subjects With Unresectable/ Metastatic Solid Tumors or Lymphomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03991559
• Other study ID #: CHN-PLAGH-BT-039
• Status: Recruiting
• Phase: Phase 1
• Start date: November 1, 2018
• Est. completion date: May 31, 2020

Study information

• Verified date: August 2019
• Source: Chinese PLA General Hospital
• Contact: Weidong Han, M.D.
• Phone: +861066937463
• Email: hanwdrsw[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Identification of T cell inhibitory signals, including PD-1/PD-L1, has prompted the development of a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. However, elimination of cancer by T cells is only one step in the Cancer-Immunity Cycle, which enable providing several therapeutic targets and tailoring of combinations of immune therapies. Manganese has been confirmed to activate antigen-presenting cells and function as mucosal immunoadjuvants in pre-clinical studies. This study is a first-in-man, Phase I, 3 + 3 dose escalation study of a combined regimen of Manganese and anti-PD-1 antibody with or without chemotherapies in subjects with unresectable/ metastatic solid tumors or lymphomas. This study is designed to assess the safety, tolerability, pharmacokinetic profile (PK profile), mode of delivery and Recommended Phase 2 Dose (RP2D) of this regimen.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: May 31, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Subjects must have histologically proven unresectable/ metastatic solid tumors or lymphomas.

2. = 18 years old.

3. Life expectancy of at least 6 months.

4. Eastern Cooperative Oncology Group performance status 0-2.

5. Subjects must have at least one measurable lesion = 1 cm as defined by response criteria.

6. Subjects must have received at least two frontline therapies, except for patients initially diagnosed with local advanced or metastatic pancreatic cancer or cholangiocarcinoma.

7. Subjects must be off prior 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. Subjects with Anti-PD-1 antibody are eligible which must be resistance.

8. Adequate organ function.

9. Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.

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. T cell lymphomas or leukemia.

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 (eg, infectious disease) illness.

Related Conditions & MeSH terms

• Lymphoma
• Solid Tumor

Intervention

Drug:
• Manganese Chloride
Administered intranasally in Arm 1 (0.05, 0.1 or 0.2 mg/kg/d) and by inhalation in Arm 2 (0.1, 0.2 or 0.4mg/kg/d) once daily in a 3-week cycle
• Anti-PD-1 antibody
Administered intravenously, at 2-4mg/kg on day 3 in a 3-week cycle

Combination Product:
• Systemic therapy
Whether and which should be given depends on the treatment regimen before enrollment.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects with treatment-related adverse events (AEs)	Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. AEs were considered to be treatment-related if they had started or worsened within the interval from first study drug administration until the follow-up visit.	Approximately 6 months
Primary	Number of subjects with specific Manganese-related adverse events	Manganese-related AEs were considered to be that start or worsen after administration Manganese administration,improve after withdrawal, and even occur again after re-administration.	Approximately 6 months
Secondary	Preliminary efficacy evaluation	Objective response rate (ORR) and disease control rate (DCR) will be evaluated by investigators per the RECIST V1.1.	Approximately 6 months
Secondary	The q3w pharmacokinetic profile of Manganese	PK parameters such as Maximum concentration (Cmax) are assessed.	Approximately 3 months
Secondary	Number of participants with laboratory test abnormalities	The laboratory tests of serum cytokines and chemokines will be performed on day 1 and 3 of each cycle, and the abnormality will be determined by the investigator.	Approximately 3 months