Lenalidomide in Combination With R-DA-EPOCH in Patients With Untreated DLBCL With MYC Rearrangement

DLBCL Clinical Trial

Official title:

A Phase II, Prospective, Single-center Study of Lenalidomide in Combination With R-DA-EPOCH in Patients With Untreated DLBCL With MYC Rearrangement

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04432714
• Other study ID #: 2019-SR-430
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 9, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: June 2020
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Li Wang, M.D., Ph.D
• Phone: 86 25 68306034
• Email: lilyw7878[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The prognosis of DLBCL with MYC rearrangement is dismal. Previous study showed that lenalidomide in combination with R-CHOP showed promising therapeutic activity and that R-DA EPOCH was superior compared to R-CHOP regimen in this cohort of patients. The investigators therefore design this phase I/II study to investigate the safety and efficacy of lenalidomide in combination with R-DA EPOCH in patients with untreated MYC-rearranged DLBCL.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 81
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Histologically confirmed DLBCL with MYC rearrangement according to WHO 2016 criteria, excluding PMBCL, PCNSL, HIV-associated lymphoma.

2. ECOG PS 0-2

3. Age 18-60 years old

4. Expected survival = 12 weeks

5. A measurable or evaluable disease at the time of enrolment (diameter =1.5cm)

6. Understand and voluntarily sign an informed consent form, able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

1. Women who are pregnant or lactating. Patients have breeding intent in 12 months or cannot take effective contraceptive measures during the trial measures

2. Active hepatitis B or hepatitis C virus infection, as well as acquired, congenital immune deficiency diseases, including but not limited to HIV infected persons

3. Previous exposure to any anti-tumor therapy

4. Poor hepatic and/or renal function, defined as total bilirubin, ALT, AST, Cr more than two fold of upper normal level,Ccr# 50 mL/min unless these abnormalities were related to the lymphoma

5. History of DVT or PE within past 12 months

6. Poor bone-marrow reserve, defined as neutrophil count less than 1.5×109/L or platelet count less than 75×109/L, unless caused by bone marrow infiltration

7. New York Heart Association class III or IV cardiac failure; or Ejection fraction less than 50%;or history of following disease in past 6 months: acute coronary syndrome#acute heart failure#severe ventricular arrhythmia

8. CNS or meningeal involvement

9. Known sensitivity or allergy to investigational product

10. Major surgery within three weeks

11. Patients receiving organ transplantation

12. Patients with secondary tumour, excluding cured (5 years without relapse) in situ Non-melanoma skin cancer. superficial bladder cancer, in situ cervical cancer, Gastrointestinal intramucous carcinoma and breast cancer

13. Presence of Grade III nervous toxicity within past two weeks

14. Active and severe infectious diseases

15. Any potential drug abuse, medical, psychological or social conditions whichmay disturb this investigation and assessment

16. In any conditions which investigator considered ineligible for this study

17. Patients with histological transformation.

Related Conditions & MeSH terms

• DLBCL
• Lymphoma, Large B-Cell, Diffuse
• MYC Gene Rearrangement
• Untreated

Intervention

Drug:
• Lenalidomide
Lenalidomide 10mg/d#15mg/d#20mg/d#25mg/d d1~d10# 21days a cycle
• Rituximab
Rituximab 375 mg/m2,IV, d0
• Etoposide
Etoposide 50 mg/m2/day CI24h d1-d4
• Doxorubicin
Doxorubicin 10 mg/m2/day CI24h d1-d4
• Vincristine
Vincristine 0.4mg/m2/day CI24h d1-d4
• Cyclophosphamide
Cyclophosphamide 750 mg/m2/day IV d5
• Prednisone
Prednisone 60 mg/m2/bid oral or IV d1-d5

Locations

Country	Name	City	State
China	The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (4)

Chamuleau MED, Burggraaff CN, Nijland M, Bakunina K, Mous R, Lugtenburg PJ, Dierickx D, van Imhoff GW, Vermaat JSP, Marijt EAF, Visser O, Mandigers C, Bilgin YM, Beeker A, Durian MF, van Rees B, Bohmer LH, Tick LW, Boersma RS, Snijders TJF, Schouten HC, Koene HR, de Jongh E, Hijmering N, Diepstra A, van den Berg A, Arens AIJ, Huijbregts J, Hoekstra O, Zijlstra JM, de Jong D, Kersten MJ. Treatment of patients with MYC rearrangement positive large B-cell lymphoma with R-CHOP plus lenalidomide: results of a multicenter HOVON phase II trial. Haematologica. 2019 Dec 19. pii: haematol.2019.238162. doi: 10.3324/haematol.2019.238162. [Epub ahead of print] — View Citation

Coiffier B, Sarkozy C. Diffuse large B-cell lymphoma: R-CHOP failure-what to do? Hematology Am Soc Hematol Educ Program. 2016 Dec 2;2016(1):366-378. Review. — View Citation

Dunleavy K, Fanale MA, Abramson JS, Noy A, Caimi PF, Pittaluga S, Parekh S, Lacasce A, Hayslip JW, Jagadeesh D, Nagpal S, Lechowicz MJ, Gaur R, Lucas A, Melani C, Roschewski M, Steinberg SM, Jaffe ES, Kahl B, Friedberg JW, Little RF, Bartlett NL, Wilson WH. Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement: a prospective, multicentre, single-arm phase 2 study. Lancet Haematol. 2018 Dec;5(12):e609-e617. doi: 10.1016/S2352-3026(18)30177-7. — View Citation

Godfrey JK, Nabhan C, Karrison T, Kline JP, Cohen KS, Bishop MR, Stadler WM, Karmali R, Venugopal P, Rapoport AP, Smith SM. Phase 1 study of lenalidomide plus dose-adjusted EPOCH-R in patients with aggressive B-cell lymphomas with deregulated MYC and BCL2. Cancer. 2019 Jun 1;125(11):1830-1836. doi: 10.1002/cncr.31877. Epub 2019 Feb 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maximum tolerated dose and dose limited toxicity		21 days after first cycle of R2-DA-EPOCH regimen (each cycle is 21 days)
Primary	Overall response rate		6 months
Secondary	Progressive free survival	from date of inclusion to date of progression, relapse, or death from any cause	2 years
Secondary	Overall survival	from the date of inclusion to date of death, irrespective of cause	2 years