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

Phase 2

Recruiting

• Conditions: Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma; Transformed Lymphoma
• Interventions: Drug: Rituximab; Drug: Etoposide; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Lenalidomide; Drug: Cisplatin; Drug: Cytarabine

• Registration Number: NCT03837873
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Brief Summary

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

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).

Study Timeline

• Study First Submitted: 2019-01-05
• Study Start: 2019-01-21
• Study First Submitted QC: 2019-02-11
• Study First Posted: 2019-02-12
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-24
• Last Update Posted: 2022-01-26
• Primary Completion: 2023-09-01
• Study Completion: 2024-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 118

Inclusion Criteria

• Histological confirmed aggressive B-cell lymphoma with one of the following subtypes:

  1. diffuse large B-cell lymphoma, NOS with at least one poor prognostic factor as follows:

     1. aaIPI 2~3(≤60 years) or IPI 3~5(>60 years);
     2. 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;
     3. CD5+ DLBCL.

  2. high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements;

  3. high-grade B-cell lymphoma, NOS

  4. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
DLCL002 protocol	Rituximab	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.
DLCL002 protocol	Etoposide	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.
DLCL002 protocol	Vincristine	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.
DLCL002 protocol	Doxorubicin	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.
DLCL002 protocol	Cyclophosphamide	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.
DLCL002 protocol	Dexamethasone	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.
DLCL002 protocol	Cisplatin	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.
DLCL002 protocol	Lenalidomide	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.
DLCL002 protocol	Cytarabine	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.

Primary Outcome Measures

Name	Time	Method
PFS	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.	progression free survival

Secondary Outcome Measures

Name	Time	Method
ORR	up to 3 months after the end of the therapy	objective response rate
EFS	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.	event free survival
OS	From the date of the start of treatment until the date of death from any cause, assessed up to 2 years.	overall survival
CRR	up to 3 months after the end of the therapy	complete response rate

Trial Locations

Locations (6)

the First Affiliated Hospital of Nanchang University; 🇨🇳 Nanchang, Jiangxi, China

Hunan Cancer Hospital; 🇨🇳 Changsha, Hunan, China

the First Affiliated Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

Qingdao Central Hospital; 🇨🇳 Qingdao, Shandong, China

the Second Hospital of Dalian Medical University; 🇨🇳 Dalian, Liaoning, China

Institute of Hematology & Blood Diseases Hospital; 🇨🇳 Tianjin, China