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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: BEAC
* Drug: Cladribine combined with BEAC


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | 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. | Baseline up to data cut-off (up to approximately 2 years) | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peripheral T-cell lymphoma, Autologous stem cell transplantation, Cladribine, BEAC