AZA Combined With RCHOP in P53-mutated DLBCL.

Study Overview
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Brief Summary
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To evaluate the efficacy and adverse effects of Azacitidine in combination with R-CHOP (ARCHOP) for the treatment of TP53-mutated previously untreated Diffuse large B-cell lymphoma

Detailed Description
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This is a Phase 2, open-label clinical trial study that aims to evaluate the efficacy (eg. Complete response, Overall Survival, Progression Free Survival) and adverse effects of Azacitidine in combination with R-CHOP (ARCHOP) for the treatment of TP53-mutated previously untreated Diffuse large B-cell lymphoma

Official Title
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A Single-arm Clinical Study of Azacitidine in Combination With R-CHOP (ARCHOP) for the Treatment of TP53-mutated Previously Untreated Diffuse Large B-cell Lymphoma

Conditions
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DLBCL - Diffuse Large B Cell Lymphoma, TP53

Intervention / Treatment
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* Drug: Azacitidine in combination with R-CHOP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (1)18-70 years old; 2) New-onset TP53 mutant DLBCL; 3) ECOG 0-2; 4) LVEF >45%; 5) HBV-positive serology (occult carriers: anti-HBeAg +, HbsAg-, anti-HBsAg +/-) only if HBV-DNA test is negative before enrollment; (6) Liver function: serum bilirubin ≤ 2.0 × ULN, serum ALT and AST ≤ 2.5 × ULN. Renal function: serum Cr ≤ 2.0 × ULN; (unless due to lymphoma); 7) Life expectancy ≥ 6 months; 8) Informed consent. Exclusion Criteria: Primary and secondary central DLBCL; HIV-positive patients and or HCV active infection; (3) Clinically significant secondary cardiovascular disease; 4) Combined hypoxemia severe chronic obstructive pulmonary disease; 5) Active bacterial, fungal, and, or viral infections not controlled by systemic therapy; 6) Apart from cured basal cell carcinoma of the skin or cervical cancer in situ or early prostate cancer not requiring systemic therapy or early breast cancer requiring only surgery alone. Within the last 3 years or concurrently with other malignant tumors; 7) Known hypersensitivity or allergic reaction to antibodies or proteins of the murine family

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARCHOP<br>Azacitidine in combination with R-CHOP | Drug: Azacitidine in combination with R-CHOP<br>* Specified dose on specified days: Azacitidine (A) 100mg subcutaneous d-1 to d-5 Rituximab (R) 375mg/m2 IV d0 Cyclophosphamide (C) 750mg/m2 IV d1 epirubicin (H) 75mg/m2 IV d1 or liposomal adriamycin (D) 25-30mg/m2 IV d1 Vincristine (O) 1.4mg/m2 (max 2mg) IV d1 Prednisone (P) 100mg orally d1-5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate (CR) | CR is evaluated according to the Lugano criteria for lymphoma response. | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial remission rate (PR) | PR is evaluated according to the Lugano criteria for lymphoma response. | Up to 36 months | 
| Overall response rate (ORR) | Percentage of participants with best overall response of partial response (PR) and complete response (CR), using the Lugano criteria. | Up to 36 months | 
| Progression Free Survival (PFS) | The Kaplan-Meier method will be used to estimate the rate of PFS. PFS was defined as the time from the date of treatment initiation until the date of the first documented day of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first. | Up to 36 months |