Diffuse Large B Cell Lymphoma
Conditions
Keywords
Diffuse Large B Cell Lymphoma, R-CHOP, Lenalidomide
Brief summary
This is a prospective single-arm, multi-center, phase II clinical trial to observe the efficacy and safety of R-CHOP (Rituximab-Cyclophosphamide, Epirubicin, Vincristine and Prednisone) combined with lenalidomide in the first-line treatment for patients with medium to high risk/high risk diffuse large B cell lymphoma.
Detailed description
Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma (NHL). Currently, R-CHOP is world-widely used in the first-line treatment for DLBCL. There are about one second of patients suffering relapse and drug resistance. Lenalidomide is an analog of thalidomide, the mechanism of anti-tumor action has not been fully elucidated. Lenalidomide has been proved to inhibit the proliferation of tumor cells in certain hematopoietic systems. At present, it has been approved for the treatment of multiple myeloma with good efficacy and safety. The goal of our trial is to assess the efficacy and safety of R-CHOP combined with lenalidomide in the first-line treatment for patients with medium to high risk/high risk diffuse large B cell lymphoma.
Interventions
DRUGRituximab
Induction Chemotherapy: 375mg/m2, Intravenous administration on day 0 of each 3-week cycle until disease progression, stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles. Maintenance Treatment for patients with CR after 6 cycles: Rituximab, 375mg/m2, Intravenous administration on day 0 repeated every 3 weeks until disease progression or unacceptable toxicity develops, up to 2 cycles (Total 8 cycles).
DRUGLenalidomide
Induction Chemotherapy: 25mg, oral administration on day 1 to 10 of each 3-week cycle until disease progression, stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.
DRUGCyclophosphamide
Induction Chemotherapy: 750mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression, stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.
DRUGEpirubicin
Induction Chemotherapy: 70mg/m2, Intravenous administration on day 1 of each 3-week cycle until disease progression, stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.
DRUGVincristine
Induction Chemotherapy: 1.4mg/m2 (Max: 2mg), Intravenous administration on day 1 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.
DRUGPrednisone
Induction Chemotherapy: 100mg, oral administration on day 1 to 5 of each 3-week cycle until disease progression/stable disease after 2 cycles treatment, partial response after 4 cycles treatment or unacceptable toxicity develops, up to 6 cycles.
DRUGMethotrexate
Induction Chemotherapy: 1g/m2, Intravenous administration on day 3 of each 3-week cycle from 2 to 5 cycles for patients with high recurrence risk of the central nervous system.
Sponsors
Henan Cancer Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
R-CHOP combined with Lenalidomide in the first-line treatment for patients with medium to high risk/high risk DLBCL. The individuals with the same propensity score according to high-risk factors (IPI score, double-expressor and P53 protein positive) were set as external control group (1:1) treated with R-CHOP.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 18 to 70 years old (including 18 and 70) 2. Diagnosed as diffuse large B cell lymphoma 3. Subjects must be untreated (medium to high risk/high risk: International Prognostic Index (IPI) score 3-5 or aaIPI score 2-3/ Immunohistochemical staining of double expression (BCL2 ≥ 50% and C-MYC ≥ 40%) or P53 protein mutation positive ≥ 50%) 4. No receiving chemotherapy before enrollment 5. Having at least one measurable lesions 6. World health organization-Eastern Cooperative Oncology Group Performance Status (ECOG) 0-2 7. Life expectancy no less than 3 months 8. enough main organ function 9. Pregnancy test within 7 days must be negative for women of childbearing period, and appropriate measures should be taken for contraception for women in childbearing period during the study and six months after this study 10. Agreeing to sign the written informed consents
Exclusion criteria
1. Diagnosed as high-grade B-cell lymphoma, including non-specified and double-strike or triple-strike 2. Diagnosed as grey-zone lymphoma 3. Diagnosed as central nervous system lymphoma 4. Diagnosed as primary mediastinal large B-cell lymphoma 5. Diagnosed as CD20 negative diffuse large B-cell lymphoma 6. Other malignant tumor history or active malignant tumor need be treated 7. Serious surgery and trauma less than two weeks 8. Systemic therapy for serious acute/chronic infection 9. Congestive heart failure, uncontrolled coronary heart disease, arrhythmia and heart infarction less than 6 months 10. Vaccination with live attenuated vaccine less than 4 weeks 11. HIV-positive, AIDS patients and untreated active hepatitis 12. Patients with a history of deep vein thrombosis or pulmonary embolism less than 12 months 13. Patients with a history of mental illness 14. Researchers determine unsuited to participate in this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-year progression-free survival | from the day of the first cycle of treatment to the date of confirmed progressive disease or death, whichever occurs first, up to 2 years after last patient's enrollment | the total proportion of patients with no progression from date of the first day of treatment to the date of confirmed progressive disease or death which one occurs first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| complete response rate | every 6 weeks from the day of the first cycle of induction chemotherapy treatment, up to 6 months after last patient's enrollment | the total proportion of patients with complete response (CR) |
| 2-year overall survival | from date of the first cycle of treatment to the date of death from any cause, assessed up to 2 years | from date of first day of treatment to the date of death by any cause |
| incidence and relationship with study drugs of grade 3-4 adverse events | from the date of the first cycle of treatment to 6 months after last patient's enrollment | the incidence and relationship with study drugs of grade 3 or 4 adverse events (based on NCI CTC-AE v4.03) |
Other
| Measure | Time frame | Description |
|---|---|---|
| exploratory endpoint | from the day of the first cycle of treatment to the date of confirmed progressive disease or death, whichever occurs first, up to 2 years after last patient's enrollment | The correlation between hotspot driven gene mutations and complete response rate, PFS, or OS |
Countries
China
Outcome results
None listed