ChiCGB vs BEAM in High-risk or R/R Lymphomas

Study Overview
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Brief Summary
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High-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) plays a vital role in treating high-risked or relapsed/refractory lymphoma. Our previous study showed chidamide combined with cladribine, gemcitabine, and busulfan (ChiCGB) as conditioning therapy improved the survival of these patients. So we designed this trial to verify if ChiCGB were better than BCNU, etoposide, cytarabine, and melphalan (BEAM). Patients with diffuse large B cell or extra-nodal NK/T cell Lymphoma who consent to this study will be randomized into the trial group who receive ChiCGB or the control group whom receive BEAM. Patients will be followed for up to 2 years after the hematopoietic cell transplantation (HCT).

Official Title
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ChiCGB Versus BEAM With Autologous Stem-Cell Transplantation in High-risk Hodgkin and Non-Hodgkin Lymphoma - A Prospective, Multi-centered, Randomized Clinical Trial

Conditions
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Lymphoma, Large B-Cell, Diffuse, Lymphoma, T-Cell

Intervention / Treatment
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* Drug: Chidamide
* Drug: Cladribine
* Drug: Gemcitabine
* Drug: Busulfan
* Drug: Carmustine
* Drug: Etoposide
* Drug: Cytarabine
* Drug: Melphalan
* Procedure: Autologous hematopoietic stem cell transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with primary refractory or recurrent diffuse large B cell lymphoma or extra-nodal NK/T cell lymphoma that do not qualify for treatment protocols of higher priority. Relapsed patients should respond to 2nd or 3rd line salvage chemotherapy and attain at least partial response before recruitment. Adequate renal function, as defined by estimated serum creatinine clearance >/=50 ml/min and/or serum creatinine </= 1.8 mg/dL. Adequate hepatic function, as defined by serum glutamate oxaloacetate transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) </= 3 x upper limit of normal; serum bilirubin and alkaline phosphatase </= 2 x upper limit of normal. Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) >/= 50% of expected corrected for hemoglobin. Adequate cardiac function with left ventricular ejection fraction >/= 50%. No uncontrolled arrhythmias or symptomatic cardiac disease. Performance status 0-1. 10. Negative Beta diffusing capacity of the lung for carbon monoxide (HCG) text in a woman with child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization Exclusion Criteria: Central nervous system lymphoma Patients relapsed after autologous stem cell transplantation Bone marrow was involved by lymphoma Patients with active hepatitis B or C(HBV DNA >/=10,000 copies/mL). Active infection requiring parenteral antibiotics HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and a normal cluster of differentiation 4 (CD4) counts Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology. Patients with a corrected QT interval(QTc) longer than 500 ms

Ages Eligible for Study
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Minimum Age: 16 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 |
| --- | --- |
| Experimental: ChiCGB<br>Treated with chidamide, cladribine, gemcitabine and busulfan(ChiCGB) therapy followed by autologous hematopoietic stem cell transplantation. | Drug: Chidamide<br>* 30 mg oral twice weekly for 2 weeks<br>Drug: Cladribine<br>* 6 mg/m2 intravenously once daily @ Day -7   -3<br>Drug: Gemcitabine<br>* 2500 mg/m2 intravenously @ Day -7, -3<br>Drug: Busulfan<br>* 3.2 mg/kg intravenously once daily @ Day -7   -4<br>Procedure: Autologous hematopoietic stem cell transplant<br>* autologous hematopoietic stem cells infusion after ChiCGB or BEAM chemotherapy<br>|
| Active Comparator: BEAM<br>Treated with BCNU, etoposide, cytarabine and melphalan (BEAM) therapy followed by autologous hematopoietic stem cell transplantation. | Drug: Carmustine<br>* 300 mg/m2 intravenously @ Day -8<br>Drug: Etoposide<br>* 200 mg/m2 intravenously once daily @ Day -7   -4<br>Drug: Cytarabine<br>* 400 mg/m2 intravenously once daily @ Day -7   -4<br>Drug: Melphalan<br>* 140 mg/m2 intravenously @ Day -3<br>Procedure: Autologous hematopoietic stem cell transplant<br>* autologous hematopoietic stem cells infusion after ChiCGB or BEAM chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | Progression free survival of this group of patients at the end of 2 year | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Overall survival of this group of patients at the end of 2 year | 2 years | 
| 100 day adverse events (AE) | non-hematologic adverse events @ Day +100 | 100 days from transplant | 
| 100 day complete response (CR) rate | Complete response @ Day +100 | 100 days from transplant |