Efficacy and Safety of Cladribine Combined With BEAC Pretreatment Regimen in the Treatment of Peripheral T-cell Lymphoma: a Multicenter Clinical Study

Sponsor

Ruijin Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04880746

Collaborator

Xinqiao Hospital of Chongqing (Other), The First Affiliated Hospital of Anhui Medical University (Other), Harbin Hematology and Oncology Institute (Other), The Affiliated Zhongshan Hospital of Dalian University (Other), Qilu Hospital of Shandong University (Other), Fujian Medical University Union Hospital (Other), Shanxi Province Cancer Hospital (Other), RenJi Hospital (Other), Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (Other), Huashan Hospital (Other)

266

Enrollment

Location

Arms

Anticipated Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This multi-center clinical study will evaluate the efficacy and safety of Cladribine Combined With BEAC Pretreatment Regimen in the Treatment of Peripheral T-cell Lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Peripheral T-cell Lymphoma	Drug: BEAC Drug: Cladribine combined with BEAC	Phase 3

Detailed Description

Peripheral T-cell lymphomas (PTCL) is a group of highly heterogeneous aggressive non-Hodgkin lymphomas originating from mature post-thymic T lymphocytes or NK/T cells. The treatment effect of patients receiving autologous hematopoietic stem cell transplantation (ASCT) is better than traditional chemotherapy, but the recurrence after transplantation is still as high as 50%. It is an urgent clinical problem to reduce the recurrence after PTCL transplantation. Cladribine can kill quiescent tumor cells, which is the main reason of tumor recurrence. Since 2018, our center has used cladribine combined with BEAC pretreatment regimen to treat 20 patients with PTCL. The PFS reached 68% at 2 years, which is about 15% higher than the previous classic BEAC regimen. This multi-center clinical study will further evaluate the efficacy and safety of Cladribine combined with BEAC pretreatment regimen in the Treatment of Peripheral T-cell Lymphoma.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

266 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Cladribine Combined With BEAC ( Semustine, Etoposide, Cytarabine, Cyclophosphamide) Pretreatment Regimen in the Treatment of Peripheral T-cell Lymphoma: a Multicenter Clinical Study

Actual Study Start Date :

Oct 17, 2020

Anticipated Primary Completion Date :

Oct 17, 2024

Anticipated Study Completion Date :

Oct 17, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: BEAC Patients in this arm will receive BEAC (Semustine, Etoposide, Cytarabine, Cyclophosphamide) as pretreatment regimen of ASCT	Drug: BEAC Semustine, 300 mg/m2，-6d； Etoposide, 100 mg/m2，-5～-2d； Cytarabine, 100mg/m2，q12h，-5～-2d； Cyclophosphamide, 1.5g/m2，-5～-2d
Experimental: Cladribine combined with BEAC Patients in this arm will receive Cladribine combined with BEAC (Semustine, Etoposide, Cytarabine, Cyclophosphamide) as pretreatment regimen of ASCT	Drug: Cladribine combined with BEAC Cladribine, 6mg/m2，-5～-2d, two hours before Cytarabine Semustine, 300 mg/m2，-6d； Etoposide, 100 mg/m2，-5～-2d； Cytarabine, 100mg/m2，q12h，-5～-2d； Cyclophosphamide, 1.5g/m2，-5～-2d

Arm

Intervention/Treatment

Active Comparator: BEAC

Patients in this arm will receive BEAC (Semustine, Etoposide, Cytarabine, Cyclophosphamide) as pretreatment regimen of ASCT

Drug: BEAC

Semustine, 300 mg/m2，-6d； Etoposide, 100 mg/m2，-5～-2d； Cytarabine, 100mg/m2，q12h，-5～-2d； Cyclophosphamide, 1.5g/m2，-5～-2d

Experimental: Cladribine combined with BEAC

Patients in this arm will receive Cladribine combined with BEAC (Semustine, Etoposide, Cytarabine, Cyclophosphamide) as pretreatment regimen of ASCT

Drug: Cladribine combined with BEAC

Cladribine, 6mg/m2，-5～-2d, two hours before Cytarabine Semustine, 300 mg/m2，-6d； Etoposide, 100 mg/m2，-5～-2d； Cytarabine, 100mg/m2，q12h，-5～-2d； Cyclophosphamide, 1.5g/m2，-5～-2d

Outcome Measures

Primary Outcome Measures

Progression free survival [Baseline up to data cut-off (up to approximately 2 years)]
Progression-free survival was defined as the time from the date of ASCT until the date of the first documented day of disease progression or relapse, using Revised Standards for Efficacy Evaluation of Malignant Lymphoma in 2007, or death from any cause, whichever occurred first.

Secondary Outcome Measures

Overall survival [Baseline up to data cut-off (up to approximately 2 years)]
Overall survival was defined as the time from the date of ASCT to the date of death from any cause.
Overall remission rate [3 months after the transplantation]
Percentage of participants with overall response was determined on the basis of Revised Standards for Efficacy Evaluation of Malignant Lymphoma in 2007.
Transplantation-related adverse reactions [Baseline up to data cut-off (up to approximately 5 years)]
Transplantation-related adverse reactions are any untoward medical occurrence in a participant which is related to ASCT
Patient tolerance [Through the whole course of ASCT, an average of one month]
Percentage of participants who can tolerate the whole treatment of ASCT
Relapse rate [Baseline up to data cut-off (up to approximately 5 years)]
Percentage of participants who relapse determined on the basis of Revised Standards for Efficacy Evaluation of Malignant Lymphoma in 2007.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18-65 years old, no gender limit;
ECOG 0-2, estimated survival time ≥ 3 months;
Pathologically newly diagnosed with PTCL (except ALK+ anaplastic large cell lymphoma), with PR or CR after 6 cycles of induction chemotherapy;
Hb≥80g/L, ANC≥1.0×10^{9/L, PLT≥75×10}9/L; TBIL≤1.5×ULN, ALT/AST≤2.0× ULN, Cr ≤1.5×ULN in the 14 days before enrollment
Have not received hematopoietic stem cell transplantation and other treatments within 4 weeks before enrollment;
The number of hematopoietic stem cells requires MNC ≥3×10^{8/kg and/or CD34 cells
≥2×10}6/kg;
Informed consented

Exclusion Criteria:

Accompanied by severe cardiac insufficiency, cardiac ejection fraction <60%; or severe arrhythmia, intolerance of pretreatment;
Accompanied by severe pulmonary insufficiency (obstructive and or restrictive ventilatory disorders), intolerance of pretreatment;
Accompanied by severe liver function impairment, liver function indexes (ALT, TBIL) are more than 3 times higher than the upper limit of normal, intolerance of pretreatment;
Accompanied by severe renal insufficiency, the renal function index (Cr) is more than 2 times the upper limit of normal; or the 24-hour urine creatinine clearance rate Ccr is less than 50ml/min, intolerance of pretreatment;
Severe active infection before transplantation, intolerance of pretreatment;
Accompanied by brain dysfunction or severe mental illness, unable to understand or follow the research plan;
Pregnant or lactation；
Accompanied by other malignant tumors in need of treatment;
Patients who cannot guarantee the completion of the necessary treatment plan and follow-up observation.