Pro-miniCHOP-like Regimen for Treatment-naive Elderly Patients

Study Overview
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Brief Summary
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The proposed study is a prospective, single-center and open-ended study in patients over the age of 70 with treatment-naive diffuse large B-cell lymphoma (DLBCL). This study intends to explore a new treatment pattern using Pro-miniCHOP-like regimen and simultaneously evaluate its safety and efficacy for future clinical practice.

Detailed Description
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The study will start with an initial 21-days of induction therapy with combination of orelabrutinib, pomalidomide and rituximab(Pro regimen) in eligible patients, following contrast computed temography(CT) to guide the next treatment. Patients whose lesions have 25% or more reduction will next receive Pro-miniCHOP-like regimen for 6 cycles. Patients with reduction less than 25% will receive R-miniCHOP-like regimen also for 6 cycles. After that, maintenance therapy with pomalidomide for two years will be given to patients undergoing Pro-miniCHOP-like regimen.

Official Title
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Prospective Exploratory Clinical Study of Orelabrutinib, Pomalidomide, Rituximab Combined With miniCHOP-like Regimen in Treatment-naive Elderly Patients With DLBCL

Conditions
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Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: Rituximab
* Drug: Orelabrutinib
* Drug: Pomalidomide
* Drug: Pro-miniCHOP-like regimen
* Drug: R-miniCHOP-like regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically or Cytologically confirmed newly diagnosed untreated DLBCL; There is at least one radiographically measurable lesion (i.e., ≥ 15mm in diameter); Age ≥ 70 years; Life expectancy >3 months; Patients with proper organic function (alanine aminotransferase, bilirubin, creatinine < 3 times the upper limit of normal; cardiac ejection fraction ≥ 50%; SPO2>90% under non-oxygenated conditions). Written informed consent obtained from the subject. Exclusion Criteria: Patients with severe liver and kidney dysfunction (alanine aminotransferase, bilirubin, creatinine > 3 times the upper limit of normal); Patients with organic heart disease with clinical symptoms or cardiac dysfunction (NYHA grade ≥2); Uncontrolled active infection; Patients with central nervous system DLBCL; A history of vascular embolism; Co-existence of other tumors; Systemic corticosteroid therapy is needed; Any other psychological conditions that prevent patients from participating in the study or signing the informed consent form.

Ages Eligible for Study
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Minimum 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: rituximab(100mg), orelabrutinib(50mg), pomalidomide(4mg), miniCHOP-like<br>Phase I(induction therapy): Patients receive Rituximab on day 1, Pomalidomide on days 1-7 and oral administration of Orelabrutinib per day. Phase II(stratified response therapy): Part A: (25% or more reduction): Patients receive Pro-miniCHOP-like regimen every 21 days for 6 cycles.(Rituximab on day 1, Pomalidomide on days 1-7, Orelabrutinib per day till progression or intolerant toxicity, Cyclophosphamide on day 2, Doxorubicin/Doxorubicin Liposome on day 2, Vindesine on day 2 and Dexamethasone on days 2-6). Part B: (reduction less than 25%): Patients receive R-miniCHOP-like regimen every 21 days for 6 cycles.(Rituximab on day 1, Cyclophosphamide on day 2, Doxorubicin/Doxorubicin Liposome on day 2, Vindesine on day 2 and Dexamethasone on days 2-6). Phase III(maintenance and follow-up): Patients take Pomalidomide orally on days 1-7 in a cycle of 21 days for 2 years. | Drug: Rituximab<br>* Rituximab 375mg/m2 ivgtt d1;<br>* Other names: MabThera;Drug: Orelabrutinib<br>* Orelabrutinib 150mg per day oral administration till progresses or intolerant toxicity;<br>* Other names: Yinuokai;Drug: Pomalidomide<br>* Pomalidomide 4mg d1-7 each cycle. After Phase II of treatment, single agent pomalidomide 4 mg d1-d7 in 21-day cycles for 2 years.<br>* Other names: Anyve;Drug: Pro-miniCHOP-like regimen<br>* rituximab 375mg/m2 ivgtt d1; orelabrutinib 150mg per day oral administration till progresses or intolerant toxicity; pomalidomide 4mg d1-7; cyclophosphamide 400mg/m2 ivgtt d2; doxorubicin 25mg/m2 ivgtt d2/ doxorubicin liposome 15 mg/m2 ivgtt d2; vindesine 2mg ivgtt d2; dexamethasone 10mg ivgtt d2-6.<br>Drug: R-miniCHOP-like regimen<br>* rituximab 375mg/m2 ivgtt d1; cyclophosphamide 400mg/m2 ivgtt d2; doxorubicin 25mg/m2 ivgtt d2/ doxorubicin liposome 15 mg/m2 ivgtt d2; vindesine 2mg ivgtt d2; dexamethasone 10mg ivgtt d2-6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate(ORR) after Pro-miniCHOP-like regimen | The rate of patients who achieved complete response and partial response after Pro-miniCHOP-like regimen. | At the end of cycle 6 (each cycle is 21 days) | 
| Complete Response Rate(CRR) after Pro-miniCHOP-like regimen | The rate of patients who achieved complete response after Pro-miniCHOP-like regimen. | At the end of cycle 6 (each cycle is 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events, treatment-related adverse events and serious adverse events | The safety and tolerability of the therapeutic regimen measured by the incidence of Treatment-Emergent Adverse Events, Treatment-Related Adverse Events and Serious Adverse Events. | Initiation of study drug until 28 days after last dose | 
| Overall Response Rate(ORR) after Pro induction regimen | The rate of patients who achieved complete response and partial response after Pro induction regimen. | At the end of a cycle 1 of induction therapy period (each cycle is 21 days) | 
| Complete Response Rate(CRR) after Pro induction regimen | The rate of patients who achieved complete response after Pro induction regimen. | At the end of a cycle 1 of induction therapy period (each cycle is 21 days) | 
| Overall Survival (OS) | OS will be assessed from the first drug given to date of death or end of follow-up. | Up to 2 years after the end of last patient's treatment | 
| Progression Free Survival (PFS) | PFS will be assessed from the first drug given to date of progression, relapse, death or end of follow-up. | Up to 2 years after the end of last patient's treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rituximab, Diffuse Large B-Cell Lymphoma, Orelabrutinib, pomalidomide