Chidamide Plus Golidocitinib in Relapsed/Refractory Peripheral T-Cell Lymphoma

NCT06757387 | Not Yet Recruiting Phase 1

• 1 other identifier: CSIIT-T42
• Study Type: interventional
• Target: 45
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase I/II, open-label, single-arm study investigating the combination of chidamide and golidocitinib in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). The Phase I portion utilizes a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of the drug combination. The Phase II portion will then evaluate the efficacy and safety of the RP2D in approximately 28 patients with relapsed or refractory PTCL. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or meeting other stopping criteria. The primary goal of Phase I is to establish the safety and MTD and the RP2D. The primary goal of Phase II is to evaluate the treatment efficacy and safety of the combination at RP2D.

Conditions

Peripheral T-cell Lymphoma

Keywords

PTCL

Outcome Measures

Primary Outcomes (1)

• dose-limiting toxicities (DLTs)

  A Dose-Limiting Toxicity (DLT) is defined as any of the following events that occur within the first cycle of combination therapy and are considered possibly related (including definitely related, probably related) to the investigational drug(s): Grade 4 neutropenia lasting for more than 5 days. Grade ≥3 neutropenia with fever (neutrophil count \<1.0 × 10\^9/L with a single temperature \>38.3°C or a temperature ≥38°C lasting for more than 1 hour). Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with a bleeding tendency. Grade 4 anemia. Grade 3 nausea or vomiting persisting for more than 48 hours despite antiemetic treatment. Grade 4 nausea or vomiting. Grade ≥3 QTc prolongation or Grade ≥2 other cardiac toxicity. Grade ≥3 non-hematologic toxicity (excluding nausea and vomiting that is not responsive to treatment). Treatment delay of more than 2 weeks in cycle 2 due to tolerability issues. Other: Clinically significant, intolerable toxicities, determined by investigator discussion t

  within 28 days

Secondary Outcomes (1)

• objective response rate (ORR)

  within 12 months

Study Arms (1)

Combination Treatment Group

EXPERIMENTAL

Dose Level 1 (chidamide 20 mg BIW / golidocitinib 150 mg QD), Dose Level 0 (chidamide 20 mg BIW / golidocitinib 150 mg QOD) will be further investigated. If the MTD is not established after escalating to Dose Level 2 (chidamide 25 mg BIW / golidocitinib 150 mg QD)

Drug: chidamide and golidocitinib

Interventions

chidamide and golidocitinib DRUG

Enrolled patients will receive combination therapy with golidocitinib (150 mg QD or 150 mg QOD) and chidamide (20 mg BIW or 25 mg BIW)； If the MTD is determined at Dose Level 1 (chidamide 20 mg BIW / golidocitinib 150 mg QD), Dose Level 0 (chidamide 20 mg BIW / golidocitinib 150 mg QOD) will be further investigated. If the MTD is not established after escalating to Dose Level 2 (chidamide 25 mg BIW / golidocitinib 150 mg QD), the recommended Phase 2 dose (RP2D) will be determined through investigator consensus.

Combination Treatment Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject must fully understand the study, voluntarily participate, and sign an informed consent form.
• The subject must be ≥ 18 years of age and ≤ 80 years of age, of either sex.
• The subject must have a histopathologically confirmed diagnosis of peripheral T-cell lymphoma (PTCL) according to the 2016 WHO classification, including peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), NK/T-cell lymphoma, anaplastic large cell lymphoma ALK-positive (ALCL ALK+), anaplastic large cell lymphoma ALK-negative (ALCL ALK-), enteropathy-associated T-cell lymphoma, and hepatosplenic T-cell lymphoma.
• The subject must have relapsed or refractory disease following prior systemic therapy (including autologous hematopoietic stem cell transplantation). Note: The subject must have received ≥1 and ≤3 prior lines of systemic therapy. Relapsed is defined as recurrence following a CR. Refractory is defined as disease with stable disease (SD) or progressive disease (PD) during interim efficacy assessment with prior systemic chemotherapy, or failure to achieve a CR at the end of treatment and need for further therapy.
• The subject must have at least one evaluable or measurable lesion according to the Lugano 2014 criteria:Lymph node lesions: Measurable lymph nodes must have a long axis \>1.5 cm.
• Non-lymph node lesions: Measurable extranodal lesions must have a long axis \>1.0 cm.
• The subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• The subject must meet the following laboratory criteria:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L. Platelet count (PLT) ≥ 100 × 10\^9/L (≥ 50 × 10\^9/L if with bone marrow infiltration).
• Hemoglobin (HB) ≥ 80 g/L. Serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the ULN.
• Serum creatinine (Scr) ≤ 1.5 times the ULN.
• The subject must not have received any radiotherapy, chemotherapy, targeted therapy, or hematopoietic stem cell transplantation within 3 weeks prior to enrollment.
• The investigator must determine that the subject has a life expectancy of at least 6 months.

You may not qualify if:

• Subjects with central nervous system (CNS) involvement and/or concomitant hemophagocytic lymphohistiocytosis (HLH).
• Prior treatment with a JAK inhibitor (e.g., golidocitinib).
• Prior treatment with an HDAC inhibitor within 3 weeks before the start of study treatment.
• Impaired cardiac function or significant cardiac disease, including, but not limited to:
• Myocardial infarction, congestive heart failure, or viral myocarditis within 6 months prior to screening; symptomatic cardiac disease requiring medical intervention, such as unstable angina or arrhythmia.
• Cardiac functional class ≥ III (New York Heart Association (NYHA) functional classification).
• Ejection fraction (EF) less than 50% or below the lower limit of normal of the study site's standard by echocardiogram.
• A history of persistent cardiomyopathy. QT corrected by Fridericia's formula (QTcF) \> 450 milliseconds, or a congenital long QT syndrome.
• Hepatitis B (positive hepatitis B surface antigen or positive hepatitis B core antibody) or Hepatitis C (positive HCV antibody or HCV-RNA titer above the upper limit of normal at the study site).
• Uncontrolled active infection (viral, bacterial, fungal, etc., such as infectious pneumonia) or a requirement for non-oral anti-infective treatment.
• Major surgery within 4-6 weeks prior to screening or scheduled major surgery during the study.
• Uncontrolled hypertension at screening, uncontrolled diabetes at screening.
• A history of active visceral bleeding within 3 months prior to screening.
• History of malignancy within the past 5 years that may interfere with protocol implementation or results analysis (with the exception of treated basal cell skin cancer, cervical carcinoma in situ, breast carcinoma in situ, in situ gastrointestinal mucosal cancer, and localized prostate cancer).
• a) Post solid organ transplant. b). A history of allogeneic hematopoietic stem cell transplantation.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

yuqin NA Song, Medical Doctor (MD)

CONTACT

+86-13910333346; zj@bjcancer.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Yuqin Song, MD, Director of Hematology Department

Study Record Dates

• First Submitted: December 13, 2024
• First Posted: January 3, 2025
• Study Start: December 30, 2024
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2030
• Last Updated: January 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share