R-ACVBP and DA-EPOCH-R in Patients With Non-GCB DLBCL

Sponsor

Nanfang Hospital of Southern Medical University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03018626

Collaborator

(none)

402

Enrollment

Location

Arms

41.2

Anticipated Duration (Months)

9.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, open-label, multi-center, phase 3 study evaluating the efficacy of R-ACVBP and DA-EPOCH-R in patients with newly diagnosed non-germinal b-cell-like diffuse large B-cell lymphoma

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Large B-Cell, Diffuse	Drug: Rituximab Drug: Etoposide Drug: Doxorubicin Drug: Vincristine Drug: Cyclophosphamide Drug: Prednisone Drug: Doxorubicin Drug: Cyclophosphamide Drug: Vindesine Drug: Bleomycin	Phase 3

Detailed Description

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. According to Hans' algorithms, DLBCL can be identified as 2 subtypes: germinal b-cell-like(GCB) and non-germinal b-cell-like(non-GCB). Approximately 50 to 60% of diffuse large-B cell lymphoma(DLBCL) was non-GCB subtype DLBCL. Although the introduction of rituximab in immunochemotherapy has dramatically improved the outcome of patients with DLBCL, The survival was still poor in non-GCB DLBCL patients treated with R-CHOP.

The LNH03-2B study has shown that R-ACVBP regimen gave a longer PFS (93% vs. 74% at 3 years, p=0.0074) and a longer OS (97% vs. 83% at 3 years, p=0.0067) than R-CHOP in young patients with non-GCB DLBCL. It also showed that R-ACVBP regimen gave a longer PFS (87% vs. 73% at 3 years, p=0.0074) and a longer OS (92% vs. 84% at 3 years, p=0.0067) than R-CHOP in young low-intermediate risk DLBCL patients. The LNH2003-3 study has shown that in high-risk (2/3 IPI factors) DLBCL patients treated with R-ACVBP followed by auto-ASCT results in a 74% PFS and 76% OS. Hematological toxic effects of the intensive regimen were raised but manageable.

The CALGB study showed that in DLBCL patients at least 18 years of age and at least stage II, DA-EPOCH-R regimen is effective in both GCB and non-GCB subtypes, with a 5-years TTP 67%, EFS 58% and OS 68% in non-GCB subtype DLBCL. It is encouraging that PETHEMA Group study showed that in the long-term follow-up of untreated DLBCL patients with poor prognosis, DA-EPOCH-R achieved a 70.8% EFS and 76.4% OS at 10 years in non-GCB subtype DLBCL.

However the efficacy of R-ACVBP compared to DA-EPOCH-R in patients with newly diagnosed non-germinal b-cell-like diffuse large B-cell lymphoma remains unknown. All the above-mentioned results led us to propose a randomized trial comparing R-ACVBP to DA-EPOCH-R in previously untreated patients with non-GCB DLBCL.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

402 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Study of R-ACVBP and DA-EPOCH-R in Patients With Newly Diagnosed Non-germinal Center B-cell-like Diffuse Large B-cell Lymphoma

Actual Study Start Date :

Jul 27, 2017

Anticipated Primary Completion Date :

Jan 1, 2020

Anticipated Study Completion Date :

Jan 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: DA-EPOCH-R DA-EPOCH-R regimen: rituximab (375 mg/m2) given intravenously (IV) on day 0, etoposide(50 mg/m2), doxorubicin(10 mg/m2) and vincristine(0.4 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours), cyclophosphamide(750 mg/m2)/dayg IV on days 5, prednisone (60 mg/m2) given orally bid on days 1 through to 5.All patients received granulocyte colony-stimulating factor (G-CSF) beginning on day 6 and continued until the ANC was more than 5 × 109/L above the nadir level. The adjustment paradigm was based on the ANC nadir in the previous cycle as previously described(Wilson, Grossbard et al. 2002)	Drug: Rituximab rituximab (375 mg/m2) given intravenously (IV) on day 0 Drug: Etoposide Etoposide(50 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours) Drug: Doxorubicin Doxorubicin(10 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours) Drug: Vincristine Vincristine(0.4 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours) Drug: Cyclophosphamide Cyclophosphamide(750 mg/m2)/dayg IV on days 5 Drug: Prednisone prednisone (100 mg) given orally bid on days 1 through to 5.
Experimental: Modified R-ACVBP R-ACVBP regimen: rituximab (375 mg/m2) given intravenously (IV) on day 0, doxorubicin (75 mg/m2) and cyclophosphamide (1,200 mg/m2) given intravenously (IV) on day 1, vindesine (2 mg/m2) given on days 1 and 5, bleomycin (10 mg) given IV on days 1 and 5, prednisone (60 mg/m2) given orally on days 1 through to 5.	Drug: Rituximab rituximab (375 mg/m2) given intravenously (IV) on day 0 Drug: Prednisone prednisone (100 mg) given orally bid on days 1 through to 5. Drug: Doxorubicin Doxorubicin (75 mg/m2) given intravenously (IV) on day 1, Drug: Cyclophosphamide Cyclophosphamide (1,200 mg/m2) given intravenously (IV) on day 1, Drug: Vindesine Vindesine (2 mg/m2) given on days 1 and 5 Drug: Bleomycin Bleomycin (10 mg) given IV on days 1 and 5

Arm

Intervention/Treatment

Active Comparator: DA-EPOCH-R

DA-EPOCH-R regimen: rituximab (375 mg/m2) given intravenously (IV) on day 0, etoposide(50 mg/m2), doxorubicin(10 mg/m2) and vincristine(0.4 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours), cyclophosphamide(750 mg/m2)/dayg IV on days 5, prednisone (60 mg/m2) given orally bid on days 1 through to 5.All patients received granulocyte colony-stimulating factor (G-CSF) beginning on day 6 and continued until the ANC was more than 5 × 109/L above the nadir level. The adjustment paradigm was based on the ANC nadir in the previous cycle as previously described(Wilson, Grossbard et al. 2002)

Drug: Rituximab

rituximab (375 mg/m2) given intravenously (IV) on day 0

Drug: Etoposide

Etoposide(50 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours)

Drug: Doxorubicin

Doxorubicin(10 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours)

Drug: Vincristine

Vincristine(0.4 mg/m2) given continuous intravenously (CIV) from day 1-4(96 hours)

Drug: Cyclophosphamide

Cyclophosphamide(750 mg/m2)/dayg IV on days 5

Drug: Prednisone

prednisone (100 mg) given orally bid on days 1 through to 5.

Experimental: Modified R-ACVBP

R-ACVBP regimen: rituximab (375 mg/m2) given intravenously (IV) on day 0, doxorubicin (75 mg/m2) and cyclophosphamide (1,200 mg/m2) given intravenously (IV) on day 1, vindesine (2 mg/m2) given on days 1 and 5, bleomycin (10 mg) given IV on days 1 and 5, prednisone (60 mg/m2) given orally on days 1 through to 5.

Drug: Rituximab

rituximab (375 mg/m2) given intravenously (IV) on day 0

Drug: Prednisone

prednisone (100 mg) given orally bid on days 1 through to 5.

Drug: Doxorubicin

Doxorubicin (75 mg/m2) given intravenously (IV) on day 1,

Drug: Cyclophosphamide

Cyclophosphamide (1,200 mg/m2) given intravenously (IV) on day 1,

Drug: Vindesine

Vindesine (2 mg/m2) given on days 1 and 5

Drug: Bleomycin

Bleomycin (10 mg) given IV on days 1 and 5

Outcome Measures

Primary Outcome Measures

Progression-free survival [3 years]

Secondary Outcome Measures

Overall survival [3 years]
Complete remission rate [about 13 weeks after initial chemotherapy]
4 cycles after chemotherapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient with histologically proven CD20+ diffuse large B cell lymphoma (WHO Classification),
aaIPI>1,
Age >18 and < 61 years,
Negative HIV serologies 4 weeks
Ability to understand and willingness to sign a written informed consent

Exclusion Criteria:

Any other histological type of lymphoma. Any history of treated or non-treated indolent lymphoma.
Central nervous system or meningeal involvement by lymphoma.
Contraindication to any drug contained in the chemotherapy regimens.
Any serious active disease (according to the investigator's decision).
Poor renal function (creatinin level>150µmol/l), poor hepatic function (total bilirubin level>30mmol/l, transaminases>2.5 maximum normal level) unless these abnormalities are related to the lymphoma.
Poor bone marrow reserve as defined by neutrophils <1.5 G/l or platelets <100 G/l, unless related to bone marrow infiltration.
Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study.
Pregnant or lactating women.