R±CEOP90 Versus R±CEOP75 in Newly Diagnosed Young Patients With Medium/High-risk DLBCL

NCT03151044 | Unknown Phase 3

• 1 other identifier: 2015NL-078
• Study Type: interventional
• Target: 408
• Locations: 1 country
• Sites: 9

Brief 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. 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.

Conditions

Diffuse Large B-cell Lymphoma

Keywords

epirubicin; high-dose; Diffuse Large B-cell Lymphoma; medium/high-risk

Outcome Measures

Primary Outcomes (1)

• 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

  up to 2 years

Secondary Outcomes (4)

• Time to response (TRR)

  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)

  From date of the first remission until the date of first documented progression, assessed up to 2 years

• Progression-free survival (PFS)

  From date of drug administration until the date of progression disease or death, whichever came first, assessed up to 2 years

• Overall survival(OS)

  From date of drug administration until the date of death, assessed up to 2 years

Study Arms (2)

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

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

Drug: Standard-dose Epirubicin Combined with CVP ± Rituximab

Interventions

High-dose Epirubicin Combined with CVP ± Rituximab DRUG

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

Also known as: R±CEOP90

EPI-90

Standard-dose Epirubicin Combined with CVP ± Rituximab DRUG

Active comparator group shall be given standard-dose Epirubicin and standard-dose Cyclophosphamide (750mg/m2), Vincristine (1.4mg/m2) and Prednisolone (100mg/m2) ± Rituximab

Also known as: R±CEOP75

EPI-75

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• 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

You may not qualify if:

• 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;
• 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

Sponsors & Collaborators

• FENG Ji-feng: lead
• Chinese Anti-Cancer Association: collaborator

Study Sites (9)

Changzhou No.2 People's Hospital

Changzhou, Jiangsu, 213003, China

RECRUITING

Jiangyin People's hospital

Jiangyin, Jiangsu, 214400, China

RECRUITING

Nanjing General Hospital

Nanjing, Jiangsu, 210002, China

RECRUITING

Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

RECRUITING

Jiangsu Cancer Institute and Hospital

Nanjing, Jiangsu, 210009, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

RECRUITING

Nantong Tumor Hospital

Nantong, Jiangsu, 226361, China

RECRUITING

Wuxi People's hospital

Wuxi, Jiangsu, 214023, China

RECRUITING

Northern Jiangsu People's Hospital

Yangzhou, Jiangsu, 225001, China

RECRUITING

Related Publications (11)

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  PMID: 14716771 BACKGROUND

• Chim 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.

  PMID: 10235070 BACKGROUND

• Lambertenghi 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.

  PMID: 7590500 BACKGROUND

• Coiffier 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.

  PMID: 11807147 BACKGROUND

• Pfreundschuh 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.

  PMID: 18226581 BACKGROUND

• Recher 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.

  PMID: 22118442 BACKGROUND

• Basaran 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.

  PMID: 11801756 BACKGROUND

• Pronzato 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.

  PMID: 9743300 BACKGROUND

• Zinzani 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.

  PMID: 2284688 BACKGROUND

• Abate 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.

  PMID: 3469805 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jifeng Feng, M.D.

  Jiangsu Cancer Institute and Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianqiu Wu, Master

CONTACT

8613951671579; drwujq@vip.126.com

Jifeng Feng, M.D.

CONTACT

8613901581264; fjif@vip.sina.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the hospital

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: May 12, 2017
• Study Start: July 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: May 12, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (9)