DLCL002 Protocol for Patients With High Risk Aggressive B-cell Lymphoma

Study Overview
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Brief Summary
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Patients eligible for the study will receive R-DA-EDOCH as the induction therapy and be evaluated by PET CT after the fourth cycle. Patients achieve CR at interim-PET(Deauville score 1-3) will receive either ASCT or the remaining 4 cycles of R-DA-EDOCH, while those achieve PR(Deauville score 4-5) will be rescued by two courses of R(2)-DHAP and then be revaluated by the second interim-PET. Patients who achieved CR+good PR(Deauville score 4) after the rescue therapy will be consolidated with ASCT,and those remain in PR(Deauville score 5) will receive other rescue treatments(including ASCT+CAR T).

Detailed Description
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Survival for patients with high risk aggressive B-cell lymphoma is still unsatisfied. Dose-intensified immunochemotherapy might improve the outcome. But for patients who could not achieve CR after the dose-intensified induction therapy, the prognosis is poor. The DLCL002 protocol is a total therapy which including induction therapy, rescue therapy and autologous stem cell transplantation. Patients eligible for the study will receive R-DA-EDOCH as the induction therapy and be evaluated by PET CT after the fourth cycle. Patients achieve CR at interim-PET(Deauville score 1-3) will receive either ASCT or the remaining 4 cycles of R-DA-EDOCH, while those achieve PR(Deauville score 4-5) will be rescued by two courses of R(2)-DHAP and then be revaluated by the second interim-PET. Patients who achieved CR+good PR(Deauville score 4) after the rescue therapy will be consolidated with ASCT,and those remain in PR(Deauville score 5) will receive other rescue treatments(including ASCT+CAR T).

Official Title
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DLCL002 Protocol for Young Patients With Newly Diagnosed High Risk Aggressive B-cell Lymphoma, a Multicenter Phase II Study

Conditions
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Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, Transformed Lymphoma

Intervention / Treatment
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* Drug: Rituximab
* Drug: Etoposide
* Drug: Vincristine
* Drug: Doxorubicin
* Drug: Dexamethasone
* Drug: Cyclophosphamide
* Drug: Lenalidomide
* Drug: Cisplatin
* Drug: Cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological confirmed aggressive B-cell lymphoma with one of the following subtypes: diffuse large B-cell lymphoma, NOS with at least one poor prognostic factor as follows: aaIPI 2 3(≤60 years) or IPI 3 5(>60 years); double protein expression lymphoma(IHC MYC≥40% and BCL2≥50%） with Ann Arbor stage of III IV or aaIPI 2 3 or IPI 3 5; CD5+ DLBCL. high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; high-grade B-cell lymphoma, NOS transformed lymphoma(no prior treatment) Age 18 to 65 years ECOG-PS: 0 2 Life-expectancy > 3 months Exclusion Criteria: Patients with central nerves system involvement HIV positivity

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DLCL002 protocol<br>Patients will receive R-DA-EDOCH(rituximab, etoposide, dexamethasone, vincristine, cyclophosphamide, doxorubicin) as induction therapy and be evaluated by PET CT after the fourth cycle. Patients achieve CR at interim-PET will receive either ASCT or the remaining 4 cycles of R-DA-EDOCH, while those achieve PR(Deauville score 4-5) will be rescued by two courses of R(2)-DHAP(rituximab, lenalidomide(only for patients with non-GCB DLBCL), dexamethasone, cisplatin, cytarabine). Patients who achieved CR+good PR(Deauville score 4) after the rescue therapy will be consolidated with ASCT,and those remain in PR(Deauville score 5) will receive other rescue treatments. | Drug: Rituximab<br>* rituximab 750mg/m2 i.v. on day 0<br>Drug: Etoposide<br>* 50mg/m2, continuous i.v. on day 1-4<br>Drug: Vincristine<br>* 0.4mg/m2, continuous i.v. on day 1-4<br>Drug: Doxorubicin<br>* 10mg/m2, continuous i.v. on day 1-4<br>Drug: Dexamethasone<br>* 30mg/day, i.v. on day 1-5 for R-DA-EDOCH regimen; 40mg/day, i.v. on day 1-4 for R(2)-DHAP regimen<br>Drug: Cyclophosphamide<br>* 750mg/m2, i.v. on day5<br>Drug: Lenalidomide<br>* 25mg/day, p.o. on day 0-9<br>Drug: Cisplatin<br>* 100mg/m2 continuous i.v. on day 1<br>Drug: Cytarabine<br>* 2g/m2 q12h, i.v. on day 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | progression free survival | From the date of the start of treatment until the date of first documented progression, relapse or death from any cause, whichever came first, assessed up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | objective response rate | up to 3 months after the end of the therapy | 
| EFS | event free survival | From the date of the start of treatment until the date of the ﬁrst adverse event (i.e. disease progression, relapse, diagnosis of a secondary malignancy, institution of a new anticancer treatment, any cause of death), assessed up to 2 years. | 
| OS | overall survival | From the date of the start of treatment until the date of death from any cause, assessed up to 2 years. | 
| CRR | complete response rate | up to 3 months after the end of the therapy |