A Umbrella Study in R/R PTCL Guided by Molecular Subtypes

A Umbrella Study in Relapsed/Refractory Peripheral T-cell Lymphoma Guided by Molecular Subtypes

This is a multicenter, prospective, open-label, interventional umbrella study to evaluate the efficacy and safety of targeted therapies guided by molecular subtypes in patients with relasped or refractory peripheral T-cell lymphoma.

Study Overview

• Status: Recruiting
• Conditions: Peripheral T Cell Lymphoma
• Intervention / Treatment: Drug: Azacitidine Injection; Drug: Dasatinib; Drug: Linperlisib; Drug: Tucidinostat; Drug: SHR2554; Drug: Camrelizumab; Drug: Apatinib

• Study Type: Interventional
• Enrollment (Anticipated): 116
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Weili Zhao; Phone Number: 610707 +862164370045; Email: zwl_trial@163.com
• Study Contact Backup: Name: Pengpeng Xu; Phone Number: 610707 +862164370045; Email: pengpeng_xu@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Weili Zhao, M.D. and Ph.D; Phone Number: 13512112076; Email: zhao.weili@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically-confirmed Peripheral T-cell lymphoma (without central nervous system involvement)
2. Relapsed or refractory disease after first line treatment
3. Availability of archival or freshly collected tumor tissue before study enrollment
4. Evaluable lesion by PET-CT or CT scan
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
6. Life expectancy greater than or equal to (>/=) 3 months
7. Informed consent

Exclusion Criteria:

1. Patients with central nervous system (CNS) lymphoma
2. History of malignancies except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
3. Uncontrolled cardio- and cerebro-vascular disease, blood clotting disorders, connective tissue diseases, serious infectious diseases and other diseases

4. Laboratory measures meet the following criteria at screening (unless caused by lymphoma):

   Neutrophils<1.0×10^9/L Platelets<75×10^9/L (Platelets<50×10^9/L in case of bone marrow involvement) ALT or AST is 2.5 times higher than the upper limits of normal (ULN), AKP and bilirubin are 1.5 times higher than the ULN.

   Creatinine is 1.5 times higher than the ULN.

5. HIV-infected patients
6. Active hepatitis infection
7. Patients with psychiatric disorders or patients who are known or suspected to be unable to fully comply with the study protocol
8. Pregnant or lactation
9. Other medical conditions determined by the researchers that may affect the study For T3.2 should exclude patiens with active autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T1 subtypes based on next generation sequencing results	Drug: Azacitidine Injection; Azacitidine Injection，SC and Dasatinib PO will be administered in T1 subtypes; Drug: Dasatinib; Azacitidine Injection，SC and Dasatinib PO will be administered in T1 subtypes
Experimental: T2 subtypes based on next generation sequencing results	Drug: Azacitidine Injection; Azacitidine Injection，SC and Dasatinib PO will be administered in T1 subtypes; Drug: Linperlisib; Azacitidine Injection，SC and Linperlisib PO will be administered in T2 subtypes
Experimental: T3.1 subtypes based on next generation sequencing results	Drug: Tucidinostat; Tucidinostat PO and SHR2554 PO will be administered in T3.1 subtypes; Drug: SHR2554; Tucidinostat PO and SHR2554 PO will be administered in T3.1 subtypes
Experimental: T3.2 subtypes based on next generation sequencing results	Drug: Camrelizumab; Camrelizumab and Apatinib will be administered in T3.2 subtypes; Drug: Apatinib; Camrelizumab and Apatinib will be administered in T3.2 subtypes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Percentage of participants with complete and partial response was determined on the basis of investigator assessments according to 2014 Lugano criteria.	End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6）(each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate	Percentage of participants with complete response was determined on the basis of investigator assessments according to 2014 Lugano criteria.	End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6）(each cycle is 28 days)
Progression-free survival	Progression-free survival was defined as the time from the date of enrollment until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first.	Baseline up to data cut-off (up to approximately 2 years)
Overall survival	Overall survival was defined as the time from the date of enrollment to the date of death from any cause.	Baseline up to data cut-off (up to approximately 2 years)
Duration of response	Duration of response was defined as the time from the date of favorable response until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria	Baseline up to data cut-off (up to approximately 2 years)
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	From enrollment to study completion, a maximum of 4 years

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2022
• Primary Completion (Anticipated): March 26, 2024
• Study Completion (Anticipated): January 26, 2026

Study Registration Dates

• First Submitted: September 25, 2022
• First Submitted That Met QC Criteria: September 27, 2022
• First Posted (Actual): September 29, 2022

Study Record Updates

• Last Update Posted (Actual): November 9, 2022
• Last Update Submitted That Met QC Criteria: November 8, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Azacitidine; Apatinib; Dasatinib
• Other Study ID Numbers: PTCL-IIT-umbrella

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No