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

Sponsor

Institute of Hematology & Blood Diseases Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03837873

Collaborator

(none)

118

Enrollment

Locations

Arm

67.4

Anticipated Duration (Months)

19.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Lymphoma High-grade B-cell Lymphoma Transformed Lymphoma	Drug: Rituximab Drug: Etoposide Drug: Vincristine Drug: Doxorubicin Drug: Dexamethasone Drug: Cyclophosphamide Drug: Lenalidomide Drug: Cisplatin Drug: Cytarabine	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

118 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 21, 2019

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DLCL002 protocol 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 rituximab 750mg/m2 i.v. on day 0 Drug: Etoposide 50mg/m2, continuous i.v. on day 1-4 Drug: Vincristine 0.4mg/m2, continuous i.v. on day 1-4 Drug: Doxorubicin 10mg/m2, continuous i.v. on day 1-4 Drug: Dexamethasone 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 Drug: Cyclophosphamide 750mg/m2, i.v. on day5 Drug: Lenalidomide 25mg/day, p.o. on day 0-9 Drug: Cisplatin 100mg/m2 continuous i.v. on day 1 Drug: Cytarabine 2g/m2 q12h, i.v. on day 2

Arm

Intervention/Treatment

Experimental: DLCL002 protocol

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

rituximab 750mg/m2 i.v. on day 0

Drug: Etoposide

50mg/m2, continuous i.v. on day 1-4

Drug: Vincristine

0.4mg/m2, continuous i.v. on day 1-4

Drug: Doxorubicin

10mg/m2, continuous i.v. on day 1-4

Drug: Dexamethasone

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

Drug: Cyclophosphamide

750mg/m2, i.v. on day5

Drug: Lenalidomide

25mg/day, p.o. on day 0-9

Drug: Cisplatin

100mg/m2 continuous i.v. on day 1

Drug: Cytarabine

2g/m2 q12h, i.v. on day 2

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hunan Cancer Hospital	Changsha	Hunan	China
2	the First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China
3	the First Affiliated Hospital of Jilin University	Changchun	Jilin	China
4	the Second Hospital of Dalian Medical University	Dalian	Liaoning	China
5	Qingdao Central Hospital	Qingdao	Shandong	China
6	Institute of Hematology & Blood Diseases Hospital	Tianjin		China	300020