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

Primary Purpose

T Cell Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
ACHOP
Sponsored by
Won Seog Kim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for T Cell Lymphoma

Eligibility Criteria

20 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. 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
  2. 20 to 85 years of age at diagnosis
  3. ECOG performance status 0-2
  4. Cardiac function suitable for chemotherapy: LVEF ≥45% on echocardiography or MUGA
  5. Appropriate renal function: Serum Cr ≤2.0mg/dL or eGFR ≥ 30mL/min according to the Cockroft-Gault formula
  6. 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)
  7. 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)
  8. Written informed consent to participate in the study
  9. Capable of following the study visit schedule and other requirements in the protocol
  10. For women of childbearing potential, a negative pregnancy test
  11. 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.
  12. Life expectancy ≥90 days (3 months)
  13. 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

Exclusion Criteria:

  1. Other subtypes of non-Hodgkin's lymphoma
  2. History of chemotherapy for Hodgkin's or other non-Hodgkin's lymphoma in the last 5 years
  3. 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)
  4. Uncontrolled hepatitis B (with the exception of asymptomatic HBsAg-positive or anti-HBcAb-positive cases receiving antiviral prophylaxis such as entecavir or tenofovir)
  5. History of chronic hepatitis C (with the exception of HCV IgG positive with a negative HCV-RNA quantification)
  6. History of human immunodeficiency virus (HIV) infection
  7. Congestive heart failure (NYHA class ≥3)
  8. Acute coronary syndrome (new-onset unstable angina or myocardial infarction) or ventricular tachycardia within 6 months prior to study entry
  9. History of major neurological or psychiatric illness, including dementia or epilepsy
  10. Severe chronic obstructive pulmonary disease with hypoxemia
  11. Cerebrovascular disease within 3 months prior to study entry (including transient cerebral ischemia)
  12. Unresolved wounds, ulcers, or bone fractures
  13. Uncontrolled active infections (viral, bacterial, or fungal infections)
  14. Concurrent use of other experimental drugs under investigation
  15. Known hypersensitivity to the investigational drugs
  16. History of major surgery or serious trauma within 21 days prior to study treatment. Open biopsy within 7 days prior to study treatment
  17. 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
  18. Pregnant or breastfeeding women or women of childbearing potential and men who are not willing to use appropriate methods of contraception during the study
  19. Previously treated for T-cell lymphoma with immunotherapy or chemotherapy, except for short-term corticosteroids (for less than 8 days) prior to selection
  20. Prior radiotherapy, except for those localized to a single lymph node
  21. Central nervous system involvement
  22. Contraindication to any of the drugs included in the chemotherapy
  23. History of administration of doxorubicin at >200 mg/m²

Sites / Locations

  • 81, Irwon-ro, Gangnam-gu, Seoul, Republic of KoreaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm ACHOP

Arm Description

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 Phase II Azacitidine D-2, -1, 1 + CHOP(Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) 6 cycles in total

Outcomes

Primary Outcome Measures

complete response rate

Secondary Outcome Measures

overall response rate
overall survival
The time until defined by date of all-cause mortality from the date of IP Administration.
Adverse events
progression-free survival
The time until defined by date of all-cause mortality from the date of Investigational Product Administration.
event-free survival
As the period from enrollment to disease progression/recurrence, treatment for other lymphomas, or death.

Full Information

First Posted
January 11, 2022
Last Updated
October 19, 2023
Sponsor
Won Seog Kim
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1. Study Identification

Unique Protocol Identification Number
NCT05230680
Brief Title
Azacitidine-CHOP for Patients With Nodal T-cell Lymphoma With T-follicular Helper Phenotype (ACANTUS)
Official Title
Multicenter, Open Label, Phase I/II of Azacitidine-CHOP for Patients With Nodal T-cell Lymphoma With T-follicular Helper Phenotype
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2022 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Won Seog Kim

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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
Detailed Description
Phase I Azacitidine will be administered intravenously from d-2 to 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. Subjects will receive intravenous 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 Phase II Azacitidine determined dose daily for D-2, -1, 1, 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) Use prophylactic trimethoprim-sulfamethoxazole 1T from the day of study drug administration to 21 days after the last dose of study treatment Administer Peg-GCSF on study d2. After Cycle 2, the study treatment can be administered if the ANC has been restored to ≥1,500/μL and platelets to ≥75,000/μL, and non-hematological toxicities that occurred in the previous cycle, except alopecia, have resolved to Grade 1 or less on d1 of each cycle. If these hematological and non-hematological toxicities are not resolved, the clinical trial can be delayed for up to 21 days. Consolidation therapy After completing the planned first-line therapy in the clinical trial, the following consolidation therapy should be performed, regardless of the azacitidine dose level. Azacitidine 75mg/m2 d1-5 (every 4 weeks, total 12 cycles)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
T Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm ACHOP
Arm Type
Experimental
Arm Description
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 Phase II Azacitidine D-2, -1, 1 + CHOP(Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) 6 cycles in total
Intervention Type
Drug
Intervention Name(s)
ACHOP
Intervention Description
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 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
Primary Outcome Measure Information:
Title
complete response rate
Time Frame
Up to 72 months
Secondary Outcome Measure Information:
Title
overall response rate
Time Frame
Up to 72 months
Title
overall survival
Description
The time until defined by date of all-cause mortality from the date of IP Administration.
Time Frame
Up to 72 months.
Title
Adverse events
Time Frame
from the day 1 of the clinical trial to 28 days after last drug administration
Title
progression-free survival
Description
The time until defined by date of all-cause mortality from the date of Investigational Product Administration.
Time Frame
Up to 72 months.
Title
event-free survival
Description
As the period from enrollment to disease progression/recurrence, treatment for other lymphomas, or death.
Time Frame
Up to 72 months.
Other Pre-specified Outcome Measures:
Title
Predictive biomarkers study
Description
analysis of blood sampling before and after the clinical trial
Time Frame
Up to 72 months.
Title
establishment of treatment response prediction model
Description
genomic analysis of tumor tissue at diagnosis
Time Frame
Up to 72 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 History of major surgery or serious trauma within 21 days prior to study treatment. Open biopsy within 7 days prior to study treatment 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 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 Central nervous system involvement Contraindication to any of the drugs included in the chemotherapy History of administration of doxorubicin at >200 mg/m²
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
kim wonseog, phD
Phone
82-10-9933-5823
Email
wonseog.kim@samsung.com
First Name & Middle Initial & Last Name or Official Title & Degree
shin hyunjung
Phone
82-2-3410-6763
Email
hjds.shin@samsung.com
Facility Information:
Facility Name
81, Irwon-ro, Gangnam-gu, Seoul, Republic of Korea
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kim Wonseog, phD
Phone
82-10-9933-5823
Email
wonseog.kim@samsung.com
First Name & Middle Initial & Last Name & Degree
shin hyunjung
Phone
82-2-3410-6763
Email
hjds.shin@samsung.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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