Efficacy and Safety of Decitabine Plus CHOP vs CHOP in Patients With Untreated Peripheral T-Cell Lymphoma

Phase 3

• Conditions: Peripheral T-cell Lymphoma
• Interventions: Drug: Decitabine; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Doxorubicin; Drug: Prednisone

• Registration Number: NCT03553537
• Lead Sponsor: Southwest Hospital, China

Brief Summary

Primary objective of the study is to compare the efficacy and safety of decitabine plus CHOP (D-CHOP) versus CHOP alone in patients with previously untreated peripheral T-cell lymphoma (PTCL).

Detailed Description

This is a randomized, multi-center, open-label study to compare efficacy and safety of D-CHOP with standard CHOP regimen in patients with previously untreated PTCL. Study subjects are patients with histologically proven PTCL. Patients are randomized 1:1 to receive either cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered in 3 week cycles for 6 cycles or decitabine plus CHOP (D-CHOP) administered in 4 week cycles for 6 cycles. In the D-CHOP arm, decitabine will be administered at a dose of 10 mg/m² IV on day 1-5 every 3 weeks. This study is divided into three phases: screening phase, treatment phase and follow-up phase. Patients will receive study drug(s) for up to 6 cycles, or until unacceptable toxicity will develop or progression or voluntary withdrawal.Adverse event of every treatment cycle will be recorded.Therapy efficacy will be evaluated after finishing 3 cycles and finishing 6 cycles therapy. Patients will be followed until disease progression, died or 2 years from the last patient randomized.

Study Timeline

• Status Verified: 2018-05
• Study First Submitted: 2018-05-30
• Study First Submitted QC: 2018-05-30
• Last Update Submitted: 2018-05-30
• Study Start: 2018-06
• Study First Posted: 2018-06-12
• Last Update Posted: 2018-06-12
• Primary Completion: 2021-07
• Study Completion: 2021-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Patients with histologically proven untreated peripheral T-cell lymphoma (include PTCL not otherwise specified, angioimmunoblastic T cell lymphoma, anapestic large cell lymphoma, enteropathy-associated T cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Nodal peripheral T-cell lymphoma with TFH phenotype and Follicular T-cell lymphoma).
2. Males and females of 18 years of age to 80 years of age.
3. Patients have not received anti-tumor therapy.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
5. Fit chemotherapy indications and basic requirements, including no obvious abnormal function of heart, liver, lung and kidney: creatine ≤2.0×ULN, total bilirubin ≤2.0mg/dl, transaminases≤3×ULN.
6. Normal peripheral hemogram: ANC≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^12/L.
7. None of other serious disease conflict with the therapeutic regimen.
8. None of other malignant tumor.
9. Pregnancy test of women at reproductive age must be negative.
10. Estimated survival time ≥ 3 months with good compliance.
11. Voluntary participation, cooperate with the experimental observation, and sign a written informed consent.

Exclusion Criteria

1. Patients with the following PTCL subtypes are excluded; extranodal NNK/T-cell lymphoma, T-prolymphocytic leukemia, T large granular lymphocytic leukemia, chronic lymphoproliferative disorder of NK cells, aggressive natural killer-cell leukemia, adult T-cell leukemia/ lymphoma, hepatosplenic T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, cutaneous T cell lymphoma, breast implant-associated anaplastic large-cell lymphoma.
2. Transformed lymphoma.
3. Patients with other malignancies in the past or now; or secondary lymphoma triggered by chemotherapy or radiotherapy of other malignancies.
4. Already initiated lymphoma therapy (exept for the prephase treatment specified for this study).
5. Patients with primary central nervous system lymphoma or lymphoma involving central nervous system.
6. Patients who have central nervous system or meninges involvements.
7. Candidate for hematopoietic stem cell transplantation.
8. Known hypersensitivity to medications to be used.
9. Hemogram abnormality: ANC<1.5×10^9/L; or HGB<90 g/L; or PLT<100×10^9/L.
10. Known hepatic and renal insufficiency (creatine>2.0×ULN, total bilirubin>2.0 mg/dl，transaminases>3.0×ULN).
11. Patients with decompensated heart failure; or with dilated cardiomyopathy; or with coronary heart disease of non-corresponding ST-segment in ECG diagnosis; or with myocardial infarction within 6 months.
12. Patients with serious uncontroled acute infection need to be treated with antibody therapies, or antiviral therapies; or serious accompanying disorder or impaired organ function.
13. Know HIV-positivity; or HbsAg positivity; or HCV-Ab positivity.
14. Pregnancy or lactation period.
15. Patients who participated in other clinical trials within 3 months.
16. The researchers considered that patients should not be in this trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CHOP regimen	Vincristine	cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered in 3 week cycles for 6 cycles
CHOP regimen	Prednisone	cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered in 3 week cycles for 6 cycles
Decitabine + CHOP regimen	Decitabine	decitabine plus CHOP (D-CHOP) administered in 4 week cycles for 6 cycles
Decitabine + CHOP regimen	Cyclophosphamide	decitabine plus CHOP (D-CHOP) administered in 4 week cycles for 6 cycles
Decitabine + CHOP regimen	Doxorubicin	decitabine plus CHOP (D-CHOP) administered in 4 week cycles for 6 cycles
Decitabine + CHOP regimen	Vincristine	decitabine plus CHOP (D-CHOP) administered in 4 week cycles for 6 cycles
Decitabine + CHOP regimen	Prednisone	decitabine plus CHOP (D-CHOP) administered in 4 week cycles for 6 cycles
CHOP regimen	Doxorubicin	cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered in 3 week cycles for 6 cycles
CHOP regimen	Cyclophosphamide	cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered in 3 week cycles for 6 cycles

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	3 years	from date of inclusion to date of progression, relapse, or death from any cause

Secondary Outcome Measures

Name	Time	Method
Overall Survival	3 years	from the date of inclusion to date of death, irrespective of cause
Response rate	3 years	complete response (CR) and partial response (PR) rates, using the standard response criteria (Cheson and al.)
Adverse Events	3 years	any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure