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

Prior treatment

• Uncontrolled hepatitis B (with the exception of asymptomatic HBsAg-positive or anti-HBcAb-positive cases receiving antiviral prophylaxis such as entecavir or tenofovir)
• Acute coronary syndrome (new-onset unstable angina or myocardial infarction) or ventricular tachycardia within 6 months prior to study entry
• Cerebrovascular disease within 3 months prior to study entry (including transient cerebral ischemia)
• Concurrent use of other experimental drugs under investigation
• Known hypersensitivity to the investigational drugs
• History of major surgery or serious trauma within 21 days prior to study treatment. Open biopsy within 7 days prior to study treatment
• Previously treated for T-cell lymphoma with immunotherapy or chemotherapy, except for short-term corticosteroids (for less than 8 days) prior to selection
• Prior radiotherapy, except for those localized to a single lymph node
• Contraindication to any of the drugs included in the chemotherapy

Other illness

• 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)
• 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)
• History of major neurological or psychiatric illness, including dementia or epilepsy
• Severe chronic obstructive pulmonary disease with hypoxemia
• Uncontrolled active infections (viral, bacterial, or fungal infections)
• History of administration of doxorubicin at \>200 mg/m²

Other

• Other subtypes of non-Hodgkin's lymphoma
• Unresolved wounds, ulcers, or bone fractures
• Male subjects who had not undergone a vasectomy and have a partner who plans to become pregnant or are unable to use a medically acceptable method of contraception (partner's sterilization or intrauterine device placement, or barrier method combined with diaphragm or condom) during the subject's participation in the study
• Pregnant or breastfeeding women or women of childbearing potential and men who are not willing to use appropriate methods of contraception during the study
• Central nervous system involvement

• 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
• 20 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)
• Hepatitis B or C infection: Hepatitis B carriers and subjects with inactive hepatitis C infection (normal levels of aminotransferases) are eligible if they take prophylactic antiviral drugs