Azacitidine-CHOP for Patients With Nodal T-cell Lymphoma With T-follicular Helper Phenotype (ACANTUS)

NCT05230680 | Recruiting Phase 1 DMC

• 1 other identifier: 2021-09-142
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Induction treatment (every 3 weeks, total 6 cycles)

• Azacitidine D-2, -1, 1 (level 1: 50mg/m2, level 2: 75mg/m2, level 3: 100mg/m2, level 4: 125mg/m2)
• Cyclophosphamide 750mg/m2 d1
• Doxorubicin 50 mg/m2 d1
• Vincristine 1.4 mg/m2 (Max: 2 mg) d1
• Prednisolone 100mg PO d1-5 Maintenance treatment (every 4 weeks, total 12 cycles)
• Azacitidine 75mg/m2 d1-5

Conditions

T Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• complete response rate

  Up to 72 months

Secondary Outcomes (5)

• overall response rate

  Up to 72 months

• overall survival

  Up to 72 months.

• Adverse events

  from the day 1 of the clinical trial to 28 days after last drug administration

• progression-free survival

  Up to 72 months.

• event-free survival

  Up to 72 months.

Other Outcomes (2)

• Predictive biomarkers study

  Up to 72 months.

• establishment of treatment response prediction model

  Up to 72 months.

Study Arms (1)

Arm ACHOP

EXPERIMENTAL

1. Phase I Azacitidine D1-3 + CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) * Level 1 - Azacitidine 50mg/m2 D-2, -1, 1 * Level 2 - Azacitidine 75mg/m2 D-2, -1, 1 * Level 3 - Azacitidine 100mg/m2 D-2, -1, 1 * Level 4 - Azacitidine 125mg/m2 D-2, -1, 1 2. Phase II * Azacitidine D-2, -1, 1 + CHOP(Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) * 6 cycles in total

Drug: ACHOP

Interventions

ACHOP DRUG

1. Phase I Azacitidine D-2\~D1, starting from dose level 1. Based on the BOIN design described above, if no DLT is identified in level 1, the dose will be escalated stepwise to levels 2, 3, and then 4. Azacitidine combined with CHOP regimen every 3 weeks as below: * Level 1 - Azacitidine 50mg/m2 D-2, -1, 1 * Level 2 - Azacitidine 75mg/m2 D-2, -1, 1 * Level 3 - Azacitidine 100mg/m2 D-2, -1, 1 * Level 4 - Azacitidine 125mg/m2 D-2, -1, 1 Azacitidine at each level will be combined with the corresponding CHOP regimen as follows: * Cyclophosphamide 750mg/m2 d1 * Doxorubicin 50 mg/m2 d1 * Vincristine 1.4 mg/m2 (Max: 2 mg) d1 * Prednisolone 100mg PO d1-5 2. Phase II * Azacitidine determined dose daily for D-2, -1, 1 * CHOP (Cyclophosphamide 750mg/m2 d1, Doxorubicin 50 mg/m2 d1, Vincristine 1.4 mg/m2 (Max: 2 mg) d1, Prednisolone 100mg PO d1-5), 6 cycles in total

Arm ACHOP

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Treatment-naïve patients with newly diagnosed nodal T-cell lymphoma with T-follicular helper (TFH) phenotype as determined by the following 2016 WHO diagnostic criteria:
• Angioimmunoblastic T-cell lymphoma
• Follicular helper T-cell lymphoma
• Peripheral T-cell lymphoma with follicular helper T-cell type
• to 85 years of age at diagnosis
• ECOG performance status 0-2
• Cardiac function suitable for chemotherapy: LVEF ≥45% on echocardiography or MUGA
• Appropriate renal function: Serum Cr ≤2.0mg/dL or eGFR ≥ 30mL/min according to the Cockroft-Gault formula
• Appropriate hepatic function: ALT ≤2.5x upper limit of normal (ULN) (or ≤5x ULN in the presence of liver involvement), total bilirubin ≤2x ULN (or ≤3x ULN in the presence of liver involvement)
• Appropriate hematologic findings: absolute neutrophil count (ANC) ≥1,500/μL, platelets ≥100,000/μL (or ANC ≥500/μL and platelets ≥50,000/ μL in the presence of bone marrow involvement)
• Written informed consent to participate in the study
• Capable of following the study visit schedule and other requirements in the protocol
• For women of childbearing potential, a negative pregnancy test
• Women of childbearing potential must use an effective method of contraception (i.e., hormonal contraception, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study period and for 3 months afterward. Men are to use an effective method of contraception during the study period and for 3 months afterward.
• Life expectancy ≥90 days (3 months)

You may not qualify if:

• Other subtypes of non-Hodgkin's lymphoma
• History of chemotherapy for Hodgkin's or other non-Hodgkin's lymphoma in the last 5 years
• History of active cancer diagnosed within the last 3 years (with the exception of completely resected non-melanoma skin cancer, papillary thyroid cancer, carcinoma in situ of cervical cancer or breast cancer, and localized prostate cancer)
• Uncontrolled hepatitis B (with the exception of asymptomatic HBsAg-positive or anti-HBcAb-positive cases receiving antiviral prophylaxis such as entecavir or tenofovir)
• History of chronic hepatitis C (with the exception of HCV IgG positive with a negative HCV-RNA quantification)
• History of human immunodeficiency virus (HIV) infection
• Congestive heart failure (NYHA class ≥3)
• Acute coronary syndrome (new-onset unstable angina or myocardial infarction) or ventricular tachycardia within 6 months prior to study entry
• History of major neurological or psychiatric illness, including dementia or epilepsy
• Severe chronic obstructive pulmonary disease with hypoxemia
• Cerebrovascular disease within 3 months prior to study entry (including transient cerebral ischemia)
• Unresolved wounds, ulcers, or bone fractures
• Uncontrolled active infections (viral, bacterial, or fungal infections)
• Concurrent use of other experimental drugs under investigation
• Known hypersensitivity to the investigational drugs

Sponsors & Collaborators

• Won Seog Kim: lead

Study Sites (1)

81, Irwon-ro, Gangnam-gu, Seoul, Republic of Korea

Seoul, 06351, South Korea

RECRUITING

MeSH Terms

Conditions

Lymphoma, T-Cell

Condition Hierarchy (Ancestors)

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

kim wonseog, phD

CONTACT

82-10-9933-5823; wonseog.kim@samsung.com

shin hyunjung

CONTACT

82-2-3410-6763; hjds.shin@samsung.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: February 9, 2022
• Study Start: July 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 23, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)