R-CHOP Versus R-CDOP as First-line Treatment for Elderly Patients With Diffuse Large-B-cell Lymphoma

Lymphoma, Large B-Cell, Diffuse Clinical Trial

Official title:

Rituximab, Cyclophosphamide, Vincristine, and Prednisone in Combination With Doxorubicin (R-CHOP) Versus in Combination With Pegylated-liposomal Doxorubicin (R-CDOP) as First-line Treatment for Elderly Patients With Diffuse Large-B-cell Lymphoma: a Randomised, Multicentre, Non-inferiority Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02428751
• Other study ID #: 308-2015-005
• Status: Recruiting
• Phase: Phase 3
• First received: April 17, 2015
• Last updated: November 17, 2015
• Start date: September 2015
• Est. completion date: May 2020

Study information

• Verified date: November 2015
• Source: Sun Yat-sen University
• Contact: Wen-qi Jiang, M.D.
• Phone: 86-20-87343765
• Email: wenqi_jiang[@]163.com
• Is FDA regulated: No
• Health authority: China: Health and Family Planning Commission of Guangdong Province
• Study type: Interventional

Clinical Trial Summary

The combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP regimen) has been the first-line chemotherapy for elderly patients with diffuse large B-cell lymphoma (DLBCL). The treatment-related toxicities, especially the severe cardiac toxicities induced by anthracycline drugs (doxorubicin), have become a major concern among elderly patients. Pegylated liposomal doxorubicin is a formulation of doxorubicin with a prolonged circulation time and unique toxicity profile. Previous single arm studies of elderly patients with lymphoma used pegylated liposomal doxorubicin instead of traditional doxorubicin in combination with rituximab, cyclophosphamide, vincristine, and prednisone (the novel R-CDOP regimen), and demonstrated better safety profile, including less bone marrow suppression and less cardiac toxicities, while maintaining the efficacy. However, the efficacy and safety of these two regimens (R-CHOP and R-CDOP) have not been head-to-head compared in a randomized study. The aim of this study is to compare the efficacy and safety of R-CDOP (rituximab, cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone) and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated elderly patients with DLBCL.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 216
• Est. completion date: May 2020
• Est. primary completion date: March 2020
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years to 80 Years

Eligibility

Inclusion Criteria:

• Pathologically confirmed diagnosis of CD20-positive diffuse large B-cell lymphoma

• 60~80 years old

• Ann Arbor stage I~IV

• ECOG physical score of 0~2

• Have not received previous treatment to lymphoma, including chemotherapy, radiotherapy, or biotherapy

• Have at least one clinically measurable lesion: >= 2cm under physical examination, or >= 1.5cm under computed tomography (CT) or magnetic resonance (MR)

• Life expectancy of >= 3 months

• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase and total bilirubin <= 2 × upper limit of normal (ULN)

• Glomerular filtration rate (MDRD method) >= 30ml/min

• No abnormalities in blood coagulative function

• Generally normal bone marrow function: while blood cell >= 3,000/µL, absolute neutrophil count >= 1,500/µL, hemoglobin >= 100g/L, platelet >= 75,000/µL

• No evidence of active hepatitis B or C virus, or human immunodeficiency virus infection

• Left ventricular ejection fraction (LVEF) >= 45% measured by two dimensional echocardiography or multi-gated acquisition (MUGA) scan

• Cardiac function of class I-II in New York Heart Association (NYHA) classification

Exclusion Criteria:

• Patients with indolent lymphoma

• Positive results for in situ hybridization for Epstein-Barr virus encoded RNA (EBER)

• Serum Epstein-Barr virus DNA >= 1,000 copies/ml

• Double-hit lymphoma confirmed by fluorescence in situ hybridization (FISH)

• Primary mediastinal B-cell lymphoma

• Involvement of central nervous system

• Bulky disease (>= 10cm)

• History of cardiac disease, including clinically significant ventricular tachycardia, atrial fibrillation, conduction block, myocardial infarction within 1 year, congestive heart failure, symptomatic coronary heart disease which needs medication

• Known allergic reaction to any component of the agents used in the chemotherapeutic regimens that are used in the study

• Previous exposure to anthracycline drugs, rituximab, or chemotherapy for lymphoma

• History of malignant carcinoma within 5 years (except carcinoma in situ of the skin and uterine cervix, and prostatic carcinoma)

• Currently enrolled in other clinical studies

• Other conditions that the investigators consider as inappropriate for enrolling into this study

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Pegylated liposomal doxorubicin
30 mg/m2, IV (in the vein) on day 1 of each 21 day cycle
• Doxorubicin
50 mg/m2, IV (in the vein) on day 1 of each 21 day cycle
• Rituximab
375 mg/m2, IV (in the vein) on day 0 of each 21 day cycle
• Cyclophophamide
750 mg/m2, IV (in the vein) on day 1 of each 21 day cycle
• Vincristine
1.4 mg/m2 (2mg in maxium), IV (in the vein) on day 1 of each 21 day cycle
• Prednisone
100mg/d, PO on day 1-5 of each 21 day cycle

Locations

Country	Name	City	State
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical Unversity	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	The Third Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	Wujing Zongdui Hospital of Guangdong Province	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Wenqi Jiang

Country where clinical trial is conducted

China, 

References & Publications (16)

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-cel — View Citation

Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing ritux — View Citation

Corazzelli G, Frigeri F, Arcamone M, Lucania A, Rosariavilla M, Morelli E, Amore A, Capobianco G, Caronna A, Becchimanzi C, Volzone F, Marcacci G, Russo F, De Filippi R, Mastrullo L, Pinto A. Biweekly rituximab, cyclophosphamide, vincristine, non-pegylate — View Citation

Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly — View Citation

Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):100 — View Citation

Gimeno E, Sánchez-González B, Alvarez-Larrán A, Pedro C, Abella E, Comín J, Saumell S, García-Pallarols F, Gómez M, Besses C, Salar A. Intermediate dose of nonpegylated liposomal doxorubicin combination (R-CMyOP) as first line chemotherapy for frail elder — View Citation

Gogas H, Papadimitriou C, Kalofonos HP, Bafaloukos D, Fountzilas G, Tsavdaridis D, Anagnostopoulos A, Onyenadum A, Papakostas P, Economopoulos T, Christodoulou C, Kosmidis P, Markopoulos C. Neoadjuvant chemotherapy with a combination of pegylated liposoma — View Citation

Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin On — View Citation

Heintel D, Skrabs C, Hauswirth A, Eigenberger K, Einberger C, Raderer M, Sperr WR, Knöbl P, Müllauer L, Uffmann M, Dieckmann K, Gaiger A, Jäger U. Nonpegylated liposomal doxorubicin is highly active in patients with B and T/NK cell lymphomas with cardiac — View Citation

Limat S, Daguindau E, Cahn JY, Nerich V, Brion A, Perrin S, Woronoff-Lemsi MC, Deconinck E. Incidence and risk-factors of CHOP/R-CHOP-related cardiotoxicity in patients with aggressive non-Hodgkin's lymphoma. J Clin Pharm Ther. 2014 Apr;39(2):168-74. doi: — View Citation

Luminari S, Montanini A, Caballero D, Bologna S, Notter M, Dyer MJ, Chiappella A, Briones J, Petrini M, Barbato A, Kayitalire L, Federico M. Nonpegylated liposomal doxorubicin (MyocetTM) combination (R-COMP) chemotherapy in elderly patients with diffuse l — View Citation

O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C; CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of — View Citation

Rigacci L, Mappa S, Nassi L, Alterini R, Carrai V, Bernardi F, Bosi A. Liposome-encapsulated doxorubicin in combination with cyclophosphamide, vincristine, prednisone and rituximab in patients with lymphoma and concurrent cardiac diseases or pre-treated w — View Citation

Tulpule A, Espina BM, Berman N, Buchanan LH, Smith DL, Sherrod A, Dharmapala D, Gee C, Boswell WD, Nathwani BN, Welles L, Levine AM. Phase I/II trial of nonpegylated liposomal doxorubicin, cyclophosphamide, vincristine, and prednisone in the treatment of — View Citation

Visani G, Guiducci B, D'Adamo F, Mele A, Nicolini G, Leopardi G, Sparaventi G, Barulli S, Malerba L, Isidori A, Malagola M, Piccaluga PP. Cyclophosphamide, pegylated liposomal doxorubicin, vincristine and prednisone (CDOP) plus rituximab is effective and — View Citation

Zaja F, Tomadini V, Zaccaria A, Lenoci M, Battista M, Molinari AL, Fabbri A, Battista R, Cabras MG, Gallamini A, Fanin R. CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma. Leuk Ly — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	event-free survival (EFS)	Defined as time from the date of randomization to the date of disease progression, death due to any cause, termination of treatment, or the most recent follow-up	two year	No
Secondary	overall response rate (ORR)	defined as the proportion of patients whose best overall response is either complete remission (CR) or partial remission (PR), which was evaluated in accordance with the International Working Group Recommendations for Response Criteria for non-Hodgkin's lymphoma	at week 6, 12, 18, and 24 after randomization	No
Secondary	complete remission (CR) rate	defined as the proportion of patients whose best overall response is complete remission, which was evaluated in accordance with the International Working Group Recommendations for Response Criteria for non-Hodgkin's lymphoma	at week 6, 12, 18, and 24 after randomization	No
Secondary	overall survival (OS)	defined as time from the date of randomization to the date of death due to any cause or the most recent follow-up	two year	No