Diffuse Large B-cell LymphomaPhase 3NCT03151044
R±CEOP90 Versus R±CEOP75 in Newly Diagnosed Young Patients With Medium/High-risk DLBCL
A Phase 3 study testing High-dose Epirubicin Combined with CVP ± Rituximab and Standard-dose Epirubicin Combined with CVP ± Rituximab in people with Diffuse Large B-cell Lymphoma, run by FENG Ji-feng at 9 sites in China.
Trial summary
This clinical trial is designed to compare the efficacy and safety of R±CEOP90 containing high-dose epirubicin and R±CEOP75 containing standard epirubicin in newly diagnosed young patients with medium/high-risk diffuse large B-cell lymphoma. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Diffuse Large B-cell Lymphoma
- What is being tested?
- High-dose Epirubicin Combined with CVP ± Rituximab and Standard-dose Epirubicin Combined with CVP ± Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 408 participants
- Where
- 9 sitesChina
- Study dates
- Jul 2016to Jul 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- All newly diagnosed patients with histologically proven diffuse large B cell lymphoma (DLBCL);
- There is at least one measurable tumor mass (physical examined long diameter of mass over 2 cm, or 5mmCT-scanned long diameter of mass over 1.5cm and short diameter over 1.0cm);
- Male or female patients aged no younger than 18 and no elder than 60 years old;
- aaIPI≥2 (LDH > normal +ECOG ≤2 + stage III-IV);
- No involvement of the central nervous system;
- ECOG score ≤ 2 points and expected survival ≥3 months;
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- During the study period, female subjects must be in menopause, or sterilization or willing to take contraceptive measures. Women with childbearing potential must use medically acceptable contraceptive method and agree to use this contraceptive method 2 weeks before treatment of the study drug, during study drug treatment and 3 months after the completion of study drug treatment;
- Male subjects are required to take contraceptive measures and agree to use this contraceptive method 2 weeks before treatment of the study drug, during study drug treatment and 3 months after the completion of study drug treatment.
- The subjects must be able to understand the study and are willing to participate in the study and sign informed consent;
- The subjects must be able and willing to follow the research plan
- Echocardiography measured LVEF ≥ 50%
- Satisfied hematological function (based on the investigator's judgment, except for the DLBCL abnormal conditions) is defined as follows: Hemoglobin ≥9g/dl; absolute neutrophil count ≥1.5 * 10^9/L; platelet count ≥75 * 10^9/L
- -
Who cannot join
- Primary central nervous system tumors or central nervous system metastasis;
- previous drug induced cardiotoxicity > =CTCAE 3.0 Grade 2;
- Complicated with serious heart disease which may affect this clinical study (e.g., heart failure [New York Heart Association NYHA Class III or IV, or left ventricular ejection fraction LVEF<50%] or with disease history of following diseases: QTc prolongation of clinical significance (for male patients, QTc over 450ms; for female patients, QTc over 470ms), ventricular tachycardia (VT) , atrial fibrillation (AF), heart block, myocardial infarction (MI) within 1 years, congestive heart failure (CHF) and coronary heart disease with symptoms requiring drug treatment;
- Diagnosis of other malignancies other than diffuse large B cell lymphoma (DLBCL);
- Mental disorders affecting compliance;
- Unable to obtain informed consent;
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- Previously have received DLBCL treatment, except for biopsy or local radiotherapy;
- Patients are pregnant or lactating women;
- Patients have severe infections, medical conditions or psychiatric conditions, and investigators believe that this condition may interfere with the purpose of the study;
- Patients with known positive human immunodeficiency virus (HIV), active hepatitis B, or active hepatitis C (positive for anti-HCV antibodies);
- Existence of following laboratory abnormalities (unless any of these abnormalities are due to underlying lymphoma):
- Creatinine was greater than 1.5 folds of upper limit of normal (ULN) (except that creatinine clearance is within normal range) or calculated creatinine clearance<40 mL/min (using Cockcroft - Gault formula)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 folds of ULN
- Total bilirubin ≥1.5 folds of ULN: if total bilirubin ≤ 3 folds of ULN, patients with diagnosed Gilbert's disease can be included
- In the absence of anticoagulant therapy, the international normalized ratio (INR) > 1.5 folds of ULN
- In lupus patients without anticoagulant drug treatment, partial thromboplastin time (PTT) and activated partial thromboplastin time (aPTT) > 1.5 folds of ULN
- Investigators decide that the patient is not suitable for this study
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
China9 sites, 9 recruiting
- Recruiting
Changzhou No.2 People's Hospital
Changzhou, Jiangsu, 213003
Xuzhang Lu, M.D., 8615295189493, luxuzhang2008@163.com
Xuzhang Lu, M.D.
- Recruiting
Jiangyin People's hospital
Jiangyin, Jiangsu, 214400
Dong Shen, M.D., 8615961663515, sdshendong@126.com
Dong Shen, M.D.
- Recruiting
Nanjing General Hospital
Nanjing, Jiangsu, 210002
Jinghua Wang, M.D., 8613951740778, jinghua56@sina.com
Jinghua Wang, M.D.
- Recruiting
Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210008
Jingyan Xu, M.D., 8613951969610, xiy1967@sina.com
Jingyan Xu, M.D.
- Recruiting
Jiangsu Cancer Institute and Hospital
Nanjing, Jiangsu, 210009
Jianqiu Wu, M.D., 8613951671579, drwujq@vip.126.com
Jifeng Feng, M.D., 8613901581264, fjif@vip.sina.com
- Recruiting
Jiangsu Province Hospital
Nanjing, Jiangsu, 210029
Xuemei Sun, M.D., 8613913911666, 13913911666@qq.com
Xuemei Sun, M.D.
- Recruiting
Nantong Tumor Hospital
Nantong, Jiangsu, 226361
Xiaohong Xu, M.D., 8618912296003, xhx107@163.com
Xiaohong Xu, M.D.
- Recruiting
Wuxi People's hospital
Wuxi, Jiangsu, 214023
Xin Zhou, M.D., 8613358111962, 13358111962@189.cn
Xin Zhou, M.D.
- Recruiting
Northern Jiangsu People's Hospital
Yangzhou, Jiangsu, 225001
Bin He, M.D., 8618932371190, yzhebin2013@qq.com
Bin He, M.D.
About this study
Official title: A Prospective, Open, Randomized Controlled, Multi-center Phase III Clinical Trial Comparing High-dose Epirubicin and Standard-dose Epirubicin in R±CEOP in Newly Diagnosed Young Patients With Medium/High-risk Diffuse Large B-cell Lymphoma
This clinical trial is designed to compare the efficacy and safety of R±CEOP90 containing high-dose epirubicin and R±CEOP75 containing standard epirubicin in newly diagnosed young patients with medium/high-risk diffuse large B-cell lymphoma. Half of the participants receive R±CEOP regimen containing 90mg/m2 epirubicin, while the other half of participants receive R±CEOP regimen containing 75mg/m2 epirubicin. Via exploring whether high-dose epirubicin shall achieve better efficacy and less toxicity, we hope to optimize current treatment choice for young patients with medium/high-risk diffuse large B-cell lymphoma.
Read the detailed description
STUDY BACKGROUND Anthracyclines are key drugs in combined chemotherapy regimen for the treatment of diffuse large B-cell lymphoma (DLBCL) and R±CHOP has been used as the first-line standard chemotherapy protocol of DLBCL. Epirubicin (EPI) belongs to anthracyclines and its mechanism of action includes directly embedding into DNA base pair, interfering with the transcription process, blocking the formation of mRNA, and thus inhibiting the synthesis of DNA and RNA. In addition, epirubicin also has inhibitory effect on topoisomerase II. Compared with adriamycin, the effect of epirubicin is equal or slightly higher, but with less cardiotoxicity and myelotoxicity.
Although epirubicin has been widely used in chemotherapy regimen for the treatment of multiple types of solid cancer, due to lack of large-scale randomized clinical study, the use of epirubicin in the treatment of lymphoma is greatly limited and epirubicin has not been recommended in internationally recognized guidelines including NCCN, ESMO and ASH. There have been several studies using epirubicin for the treatment of lymphoma, which all indicated comparable efficacy and lower toxicity compared with adriamycin. Because CHOP regimen is often combined with targeted therapy, optimizing anthracyclines in CHOP regimen is quite important for reducing toxicity, especially replacing Adriamycin with epirubicin.
Up to present, there have been studies on elderly patients and low-risk young patients with DLBCL and the results have provided evidences to support R+CHOP21 as the first-line standard therapy for DLBCL. But there still lacks clinical studies on high-risk young DLBCL patients and the treatment for these kinds of patients often follows the therapy of above mentioned studies, and these lack strong support of evidenced medicine. Before the application of Rituximab, several studies have suggested that increasing dosage strength of anthracyclines may bring benefits in overall survival to patients. After the introduction of Rituximab in the treatment of DLBCL, although Rituximab significantly promote overall survival of low-risk patients, young high-risk patients have not been studied.
Based on above background and current knowledge gap, this clinical study shall focus on newly pathologically diagnosed young medium/high-risk Chinese DLBCL patients and investigate whether enhanced epirubicin dosage strength shall achieve higher complete remission rate and longer overall survival.
OBJECTIVES:
- Evaluate and compare the efficacy of high-dose epirubicin (90mg/m2) and standard-dose epirubicin (75mg/m2) in R±CEOP chemotherapy regimen.
- Assess toxicity profile of R±CEOP chemotherapy regimen at different dosage of epirubicin, especially difference in cardiotoxicity and hematological toxicity between R±CEOP90 and R±CEOP75.
- Assess the influence of R±CEOP90 and R±CEOP75 on long-term survival of newly diagnosed young patients with medium/high-risk diffuse large B-cell lymphoma.
OUTLINE:
Included patients shall be randomly divided into 2 groups: high-dose epirubicin group (90mg/m2) and standard-dose epirubicin group (75mg/m2) given intravenously on Day 1 of each cycle for totally 6 cycles. Patients with CD20 positive proven by pathological examination in both groups shall receive Rituximab. Except for the difference in epirubicin dosage, the administration of Cyclophosphamide, Vincristine and Prednisolone shall follow standard chemotherapy regimen.
Screening shall be completed within 4 weeks before the administration of study drugs. For included patients, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. During treatment of study drugs, the tests and procedures shall be performed within the first 3 days of each cycle: serum chemistry test, hematological test and body weight measurement. Physical examination, vital sign and WHO performance and ECOG score shall be performed or assess before the administration of study drugs on Day 1 of each cycle. At the end of Cycle 3, 6 and 8 (if applicable) (±14days), physical examination, CT or MRI or PET examination shall be performed. If necessary, bone marrow assessment shall also be performed.
End-of-treatment visit shall be conducted within 4-5 weeks after the last administration of study drug. Patients experiencing toxicity or side effects shall be assessed within 4 weeks after withdrawal of study drugs. After completion of study treatment, patients who have not shown signs of disease progression shall be followed up for 2 year until disease progression, start treatment for another disease or death. Follow-up visit shall be conducted every 12±2 weeks and tumor assessment shall be performed (including neck, chest, abdomen, and pelvis CT or MRI).
PROJECTED ACCRUAL: A total of 408 patients will be accrued for this study.
- Conditions
- Diffuse Large B-cell Lymphoma
- Being tested
- High-dose Epirubicin Combined with CVP ± Rituximab, Standard-dose Epirubicin Combined with CVP ± Rituximab
- Keywords
- epirubicin, high-dose, Diffuse Large B-cell Lymphoma, medium/high-risk
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-dose Epirubicin Combined with CVP ± RituximabDrug
Also called R±CEOP90
Experimental group shall be given high-dose Epirubicin (90mg/m2) combined with standard-dose Cyclophosphamide (750mg/m2), Vincristine (1.4mg/m2) and Prednisolone (100mg/m2) ± Rituximab
Standard-dose Epirubicin Combined with CVP ± RituximabDrug
Also called R±CEOP75
Active comparator group shall be given standard-dose Epirubicin and standard-dose Cyclophosphamide (750mg/m2), Vincristine (1.4mg/m2) and Prednisolone (100mg/m2) ± Rituximab
| Study group | Role | What they receive |
|---|---|---|
| EPI-90 | Experimental | Participants in this arm shall be given high-dose Epirubicin Combined with CVP ± Rituximab for six 21-day cycles:
High-dose Epirubicin 90mg/m2, i.v., Day 1; Cyclophosphamide 750mg/m2, i.v., Day 1; Vincristine 1.4mg/m2, i.v., Day 1; Prednisolone 100mg/m2, p.o., Day 1-5;
Plus/not plus:
Rituximab 375mg/m2, i.v., Day 0 Receives: Drug: High-dose Epirubicin Combined with CVP ± Rituximab |
| EPI-75 | Active comparator | Participants in this arm shall be given standard-dose Epirubicin, Combined with CVP ± Rituximab for six 21-day cycles:
Standard-dose Epirubicin 75mg/m2, i.v., Day 1; Cyclophosphamide 750mg/m2, i.v., Day 1; Vincristine 1.4mg/m2, i.v., Day 1; Prednisolone 100mg/m2, p.o., Day 1-5;
Plus/not plus:
Rituximab 375mg/m2, i.v., Day 0 Receives: Drug: Standard-dose Epirubicin Combined with CVP ± Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Percentage of Complete remission (CR), Unconfirmed Complete Remission (CRu) and Partial remission (PR), referred to 2007 Cheson's Response Criteria for Lymphoma
Measured: up to 2 years
Secondary outcomes (4)
Time to response (TRR)
The time from drug administration to the first remission (including the first PR, CRu and CR)
Measured: From date of drug administration until the date of the first remission (including Complete remission, Unconfirmed Complete Remission and Partial remission, whichever came first), assessed up to 2 years
Duration of response (DOR)
The time from remission to the first disease progression
Measured: From date of the first remission until the date of first documented progression, assessed up to 2 years
Progression-free survival (PFS)
The time from drug administration to the first progression disease or death
Measured: From date of drug administration until the date of progression disease or death, whichever came first, assessed up to 2 years
Overall survival(OS)
The time from drug administration to death
Measured: From date of drug administration until the date of death, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2017
- Study startJul 2016
- Primary completionJul 2017 (estimated)
- Study completionJul 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 408 participants (estimated)
Sponsor and investigators
- Lead sponsor
- FENG Ji-feng
- Sponsor type
- University, hospital or other
- Collaborators
- Chinese Anti-Cancer Association
- Responsible party
- Sponsor-investigator, FENG Ji-feng, Jiangsu Cancer Institute & Hospital
- Investigators
- Jifeng Feng, M.D., Principal investigator, Jiangsu Cancer Institute and Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03151044
- Sponsor's protocol ID
- 2015NL-078
- Status last verified
- May 2017
- First submitted
- 9 May 2017
- Last updated
- 12 May 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Economopoulos T, Dimopoulos MA, Mellou S, Pavlidis N, Samantas E, Nicolaides C, Tsatalas C, Papadopoulos A, Papageogriou E, Papasavvas P, Fountzilas G. Treatment of intermediate- and high-grade non-Hodgkin's lymphoma using CEOP versus CNOP. Eur J Haematol. 2002 Mar;68(3):135-43. doi: 10.1034/j.1600-0609.2002.01620.x.
PubMed 12068793Rossini F, Terruzzi E, Perego D, Miccolis I, Rivolta F, Manca E, Pogliani EM. Long-term follow-up of patients with intermediate or high-grade non-Hodgkin lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine, and prednisone. Cancer. 2004 Jan 15;100(2):350-5. doi: 10.1002/cncr.11907.
PubMed 14716771Chim CS, Kwong YL, Lie AK, Lee CK, Liang R. CEOP treatment results and validity of the International Prognostic Index in Chinese patients with aggressive non-Hodgkin's lymphoma. Hematol Oncol. 1998 Sep;16(3):117-23. doi: 10.1002/(sici)1099-1069(199809)16:33.0.co;2-0.
PubMed 10235070Lambertenghi Deliliers G, Butti C, Baldini L, Ceriani A, Lombardi F, Luoni M, Montalbetti L, Pavia G, Pinotti G, Pogliani E, et al. A cooperative study of epirubicin with cyclophosphamide, vincristine and prednisone (CEOP) in non-Hodgkin's lymphoma. Haematologica. 1995 Jul-Aug;80(4):318-24.
PubMed 7590500Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. doi: 10.1056/NEJMoa011795.
PubMed 11807147Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trumper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. doi: 10.1016/S1470-2045(08)70002-0. Epub 2008 Jan 15.
PubMed 18226581Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O, Thieblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquieres H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. doi: 10.1016/S0140-6736(11)61040-4.
PubMed 22118442Basaran M, Bavbek ES, Sakar B, Eralp Y, Alici S, Tas F, Yaman F, Dogan O O, Camlica H, Onat H. Treatment of aggressive non-Hodgkin's lymphoma with dose-intensified epirubicin in combination of cyclophosphamide, vincristine, and prednisone (CEOP-100): a phase II study. Am J Clin Oncol. 2001 Dec;24(6):570-5. doi: 10.1097/00000421-200112000-00008.
PubMed 11801756Pronzato P, Lionetto R, Botto F, Pensa F, Tognoni A. High-dose intensity cyclophosphamide, epidoxorubicin, vincristine and prednisone by shortened intervals and granulocyte colony-stimulating factor in non-Hodgkin's lymphoma: a phase II study. Br J Cancer. 1998 Sep;78(6):777-80. doi: 10.1038/bjc.1998.578.
PubMed 9743300Zinzani PL, Mazza P, Gherlinzoni F, Zanchini R, Bocchia M, Aitini E, Cavazzini G, Amurri B, Gobbi M, Tura S. CEOP regimen in the treatment of advanced low-grade non-Hodgkin's lymphomas: preliminary report. Tumori. 1990 Dec 31;76(6):533-6. doi: 10.1177/030089169007600603.
PubMed 2284688Abate G, Comella P, Di Pietro N, Ganzina F, Pergola M, Silvestro P, Basso A, Salvatore M, Zarrilli D. Epirubicin in combination chemotherapy in the treatment of advanced stage non-Hodgkin's lymphomas. Tumori. 1987 Feb 28;73(1):43-7. doi: 10.1177/030089168707300108.
PubMed 3469805
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Open, Randomized Controlled, Multi-center Phase III Clinical Trial Comparing High-dose Epirubicin and Standard-dose Epirubicin in R±CEOP in Newly Diagnosed Young Patients With Medium/High-risk Diffuse Large B-cell Lymphoma
- ClinicalTrials.gov ID
- NCT03151044
- Acronym / sponsor ID
- 2015NL-078
- Conditions
- Diffuse Large B-cell Lymphoma
- Keywords
- epirubicin, high-dose, Diffuse Large B-cell Lymphoma, medium/high-risk
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 408 participants (estimated)
- Lead sponsor
- FENG Ji-fengUniversity, hospital or other
- Collaborators
- Chinese Anti-Cancer Association
- Study start
- Jul 2016 (actual)
- Primary completion
- Jul 2017 (estimated)
- Study completion
- Jul 2017 (estimated)
- First posted
- 12 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial is designed to compare the efficacy and safety of R±CEOP90 containing high-dose epirubicin and R±CEOP75 containing standard epirubicin in newly diagnosed young patients with medium/high-risk diffuse large B-cell lymphoma. Half of the participants receive R±CEOP regimen containing 90mg/m2 epirubicin, while the other half of participants receive R±CEOP regimen containing 75mg/m2 epirubicin. Via exploring whether high-dose epirubicin shall achieve better efficacy and less toxicity, we hope to optimize current treatment choice for young patients with medium/high-risk diffuse large B-cell lymphoma.
Detailed description
STUDY BACKGROUND Anthracyclines are key drugs in combined chemotherapy regimen for the treatment of diffuse large B-cell lymphoma (DLBCL) and R±CHOP has been used as the first-line standard chemotherapy protocol of DLBCL. Epirubicin (EPI) belongs to anthracyclines and its mechanism of action includes directly embedding into DNA base pair, interfering with the transcription process, blocking the formation of mRNA, and thus inhibiting the synthesis of DNA and RNA. In addition, epirubicin also has inhibitory effect on topoisomerase II. Compared with adriamycin, the effect of epirubicin is equal or slightly higher, but with less cardiotoxicity and myelotoxicity.
Although epirubicin has been widely used in chemotherapy regimen for the treatment of multiple types of solid cancer, due to lack of large-scale randomized clinical study, the use of epirubicin in the treatment of lymphoma is greatly limited and epirubicin has not been recommended in internationally recognized guidelines including NCCN, ESMO and ASH. There have been several studies using epirubicin for the treatment of lymphoma, which all indicated comparable efficacy and lower toxicity compared with adriamycin. Because CHOP regimen is often combined with targeted therapy, optimizing anthracyclines in CHOP regimen is quite important for reducing toxicity, especially replacing Adriamycin with epirubicin.
Up to present, there have been studies on elderly patients and low-risk young patients with DLBCL and the results have provided evidences to support R+CHOP21 as the first-line standard therapy for DLBCL. But there still lacks clinical studies on high-risk young DLBCL patients and the treatment for these kinds of patients often follows the therapy of above mentioned studies, and these lack strong support of evidenced medicine. Before the application of Rituximab, several studies have suggested that increasing dosage strength of anthracyclines may bring benefits in overall survival to patients. After the introduction of Rituximab in the treatment of DLBCL, although Rituximab significantly promote overall survival of low-risk patients, young high-risk patients have not been studied.
Based on above background and current knowledge gap, this clinical study shall focus on newly pathologically diagnosed young medium/high-risk Chinese DLBCL patients and investigate whether enhanced epirubicin dosage strength shall achieve higher complete remission rate and longer overall survival.
OBJECTIVES:
- Evaluate and compare the efficacy of high-dose epirubicin (90mg/m2) and standard-dose epirubicin (75mg/m2) in R±CEOP chemotherapy regimen.
- Assess toxicity profile of R±CEOP chemotherapy regimen at different dosage of epirubicin, especially difference in cardiotoxicity and hematological toxicity between R±CEOP90 and R±CEOP75.
- Assess the influence of R±CEOP90 and R±CEOP75 on long-term survival of newly diagnosed young patients with medium/high-risk diffuse large B-cell lymphoma.
OUTLINE:
Included patients shall be randomly divided into 2 groups: high-dose epirubicin group (90mg/m2) and standard-dose epirubicin group (75mg/m2) given intravenously on Day 1 of each cycle for totally 6 cycles. Patients with CD20 positive proven by pathological examination in both groups shall receive Rituximab. Except for the difference in epirubicin dosage, the administration of Cyclophosphamide, Vincristine and Prednisolone shall follow standard chemotherapy regimen.
Screening shall be completed within 4 weeks before the administration of study drugs. For included patients, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. During treatment of study drugs, the tests and procedures shall be performed within the first 3 days of each cycle: serum chemistry test, hematological test and body weight measurement. Physical examination, vital sign and WHO performance and ECOG score shall be performed or assess before the administration of study drugs on Day 1 of each cycle. At the end of Cycle 3, 6 and 8 (if applicable) (±14days), physical examination, CT or MRI or PET examination shall be performed. If necessary, bone marrow assessment shall also be performed.
End-of-treatment visit shall be conducted within 4-5 weeks after the last administration of study drug. Patients experiencing toxicity or side effects shall be assessed within 4 weeks after withdrawal of study drugs. After completion of study treatment, patients who have not shown signs of disease progression shall be followed up for 2 year until disease progression, start treatment for another disease or death. Follow-up visit shall be conducted every 12±2 weeks and tumor assessment shall be performed (including neck, chest, abdomen, and pelvis CT or MRI).
PROJECTED ACCRUAL: A total of 408 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EPI-90 | Experimental | Drug: High-dose Epirubicin Combined with CVP ± RituximabParticipants in this arm shall be given high-dose Epirubicin Combined with CVP ± Rituximab for six 21-day cycles: High-dose Epirubicin 90mg/m2, i.v., Day 1; Cyclophosphamide 750mg/m2, i.v., Day 1; Vincristine 1.4mg/m2, i.v., Day 1; Prednisolone 100mg/m2, p.o., Day 1-5; Plus/not plus: Rituximab 375mg/m2, i.v., Day 0 |
| EPI-75 | Active comparator | Drug: Standard-dose Epirubicin Combined with CVP ± RituximabParticipants in this arm shall be given standard-dose Epirubicin, Combined with CVP ± Rituximab for six 21-day cycles: Standard-dose Epirubicin 75mg/m2, i.v., Day 1; Cyclophosphamide 750mg/m2, i.v., Day 1; Vincristine 1.4mg/m2, i.v., Day 1; Prednisolone 100mg/m2, p.o., Day 1-5; Plus/not plus: Rituximab 375mg/m2, i.v., Day 0 |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- All newly diagnosed patients with histologically proven diffuse large B cell lymphoma (DLBCL);
- There is at least one measurable tumor mass (physical examined long diameter of mass over 2 cm, or 5mmCT-scanned long diameter of mass over 1.5cm and short diameter over 1.0cm);
- Male or female patients aged no younger than 18 and no elder than 60 years old;
- aaIPI≥2 (LDH > normal +ECOG ≤2 + stage III-IV);
- No involvement of the central nervous system;
Key exclusion criteria (17 listed)
- Primary central nervous system tumors or central nervous system metastasis;
- previous drug induced cardiotoxicity > =CTCAE 3.0 Grade 2;
- Complicated with serious heart disease which may affect this clinical study (e.g., heart failure [New York Heart Association NYHA Class III or IV, or left ventricular ejection fraction LVEF<50%] or with disease history of following diseases: QTc prolongation of clinical significance (for male patients, QTc over 450ms; for female patients, QTc over 470ms), ventricular tachycardia (VT) , atrial fibrillation (AF), heart block, myocardial infarction (MI) within 1 years, congestive heart failure (CHF) and coronary heart disease with symptoms requiring drug treatment;
- Diagnosis of other malignancies other than diffuse large B cell lymphoma (DLBCL);
- Mental disorders affecting compliance;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High-dose Epirubicin Combined with CVP ± RituximabAlso: R±CEOP90Experimental group shall be given high-dose Epirubicin (90mg/m2) combined with standard-dose Cyclophosphamide (750mg/m2), Vincristine (1.4mg/m2) and Prednisolone (100mg/m2) ± Rituximab | Drug | EPI-90 |
| Standard-dose Epirubicin Combined with CVP ± RituximabAlso: R±CEOP75Active comparator group shall be given standard-dose Epirubicin and standard-dose Cyclophosphamide (750mg/m2), Vincristine (1.4mg/m2) and Prednisolone (100mg/m2) ± Rituximab | Drug | EPI-75 |
Primary outcome
Objective Response Rate (ORR)
Time frame: up to 2 years
Percentage of Complete remission (CR), Unconfirmed Complete Remission (CRu) and Partial remission (PR), referred to 2007 Cheson's Response Criteria for Lymphoma
4 secondary outcomes
Time to response (TRR)
Time frame: From date of drug administration until the date of the first remission (including Complete remission, Unconfirmed Complete Remission and Partial remission, whichever came first), assessed up to 2 years
Duration of response (DOR)
Time frame: From date of the first remission until the date of first documented progression, assessed up to 2 years
Progression-free survival (PFS)
Time frame: From date of drug administration until the date of progression disease or death, whichever came first, assessed up to 2 years
Overall survival(OS)
Time frame: From date of drug administration until the date of death, assessed up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2017.
- Background: PubMed 12068793Economopoulos T, Dimopoulos MA, Mellou S, Pavlidis N, Samantas E, Nicolaides C, Tsatalas C, Papadopoulos A, Papageogriou E, Papasavvas P, Fountzilas G. Treatment of intermediate- and high-grade non-Hodgkin's lymphoma using CEOP versus CNOP. Eur J Haematol. 2002 Mar;68(3):135-43. doi: 10.1034/j.1600-0609.2002.01620.x.
- Background: PubMed 14716771Rossini F, Terruzzi E, Perego D, Miccolis I, Rivolta F, Manca E, Pogliani EM. Long-term follow-up of patients with intermediate or high-grade non-Hodgkin lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine, and prednisone. Cancer. 2004 Jan 15;100(2):350-5. doi: 10.1002/cncr.11907.
- Background: PubMed 10235070Chim CS, Kwong YL, Lie AK, Lee CK, Liang R. CEOP treatment results and validity of the International Prognostic Index in Chinese patients with aggressive non-Hodgkin's lymphoma. Hematol Oncol. 1998 Sep;16(3):117-23. doi: 10.1002/(sici)1099-1069(199809)16:33.0.co;2-0.
- Background: PubMed 7590500Lambertenghi Deliliers G, Butti C, Baldini L, Ceriani A, Lombardi F, Luoni M, Montalbetti L, Pavia G, Pinotti G, Pogliani E, et al. A cooperative study of epirubicin with cyclophosphamide, vincristine and prednisone (CEOP) in non-Hodgkin's lymphoma. Haematologica. 1995 Jul-Aug;80(4):318-24.
- Background: PubMed 11807147Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. doi: 10.1056/NEJMoa011795.
- Background: PubMed 18226581Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trumper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. doi: 10.1016/S1470-2045(08)70002-0. Epub 2008 Jan 15.
- Background: PubMed 22118442Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O, Thieblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquieres H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. doi: 10.1016/S0140-6736(11)61040-4.
- Background: PubMed 11801756Basaran M, Bavbek ES, Sakar B, Eralp Y, Alici S, Tas F, Yaman F, Dogan O O, Camlica H, Onat H. Treatment of aggressive non-Hodgkin's lymphoma with dose-intensified epirubicin in combination of cyclophosphamide, vincristine, and prednisone (CEOP-100): a phase II study. Am J Clin Oncol. 2001 Dec;24(6):570-5. doi: 10.1097/00000421-200112000-00008.
- Background: PubMed 9743300Pronzato P, Lionetto R, Botto F, Pensa F, Tognoni A. High-dose intensity cyclophosphamide, epidoxorubicin, vincristine and prednisone by shortened intervals and granulocyte colony-stimulating factor in non-Hodgkin's lymphoma: a phase II study. Br J Cancer. 1998 Sep;78(6):777-80. doi: 10.1038/bjc.1998.578.
- Background: PubMed 2284688Zinzani PL, Mazza P, Gherlinzoni F, Zanchini R, Bocchia M, Aitini E, Cavazzini G, Amurri B, Gobbi M, Tura S. CEOP regimen in the treatment of advanced low-grade non-Hodgkin's lymphomas: preliminary report. Tumori. 1990 Dec 31;76(6):533-6. doi: 10.1177/030089169007600603.
- Background: PubMed 3469805Abate G, Comella P, Di Pietro N, Ganzina F, Pergola M, Silvestro P, Basso A, Salvatore M, Zarrilli D. Epirubicin in combination chemotherapy in the treatment of advanced stage non-Hodgkin's lymphomas. Tumori. 1987 Feb 28;73(1):43-7. doi: 10.1177/030089168707300108.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jifeng Feng, M.D. principal investigator
Jiangsu Cancer Institute and Hospital
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing High-dose Epirubicin Combined with CVP ± Rituximab and Standard-dose Epirubicin Combined with CVP ± Rituximab in people with Diffuse Large B-cell Lymphoma, run by FENG Ji-feng at 9 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jianqiu Wu, Master (8613951671579, drwujq@vip.126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03151044, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2017.