R-EPOCH in Combination With Ibrutinib for Patients With Classical RT of CLL

Richter Transformation Clinical Trial

— BDHRT001  

Official title:

A Multicenter Phase 2 Study of R-EPOCH in Combination With Ibrutinib for Patients With Classical Richter Transformation of Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04992377
• Other study ID #: IHBDH-IIT2021015
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: August 30, 2021
• Est. completion date: August 30, 2025

Study information

• Verified date: July 2021
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: Tingyu Wang
• Phone: +86 15692201678
• Email: wangtingyu[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an investigator-initiated Phase 2 study, which combines R-EDOCH with Ibrutinib to treat patients with Ritcher Transformation in consideration of DLBCL and CLL components both could being targeted at the same time. The investigator will observe the 2-year overall survival rate of this regimen for RT and explore the new regimen for RT in the novel drugs era, which aims to improve the efficacy and prolong survival.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: August 30, 2025
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Age 18-65 years

2. ECOG 0-2

3. Confirmed Richter transformation, whether or not previously treated

4. Unexposed to BTKi, or discontinue BTKi more than 1 year (due not to toxicity or ineffectiveness)

5. No serious liver, kidney, heart and other complications; including: a. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 times the upper limit of normal (ULN); b. total bilirubin (TBIL) = 1.5 times the ULN; c. serum creatinine (Cr) = 2 times the ULN, or glomerular filtration rate = 40ml/min; d. LVEF > 50% determined by echocardiography; e. no arrhythmia and active heart disease, such as coronary heart disease, myocardial infarction, etc

6. The patient agreed to participate and signed the informed consent form

Exclusion Criteria:

1. Major surgery within 4 weeks prior to first dose of ibrutinib

2. Require receiving anticoagulation with warfarin or equivalent Vitamin K antagonists; Requires treatment with a strong CYP3A4/5 inhibitor

3. Require corticosteroid , anti-cancer drugs, immunomodulatory or Chinese medicine for other medical conditions

4. Pregnant or lactating women

5. History of prior malignancy

6. Currently active clinically significant cardiovascular disease

7. Uncontrolled active systemic fungal, bacterial, viral, or other infection

8. Known history of human immunodeficiency virus (HIV) or active infection with Hepatitis B or Hepatitis C

9. History of stroke or intracranial hemorrhage prior to randomization

10. Other conditions that is unfit for the clinical trial in the investigator' opinion

Related Conditions & MeSH terms

• Richter Transformation

Intervention

Drug:
• R-EPOCH in Combination With Ibrutinib
Induction: (21-day per cycle) Ibrutinib:420mg given orally , once daily. Details of R-DA-EPOCH are as follows: Rituximab: 375 mg/m2 given intravenously (IV) on day 0 Etoposide: 50 mg/m2 given CIV from day 1-4 Doxorubicin: 10 mg/m2 given CIV from day 1-4 Vincristine: 0.4 mg/m2 given CIV from day 1-4 Cyclophosphamide: 750 mg/m2/day IV on day 5 Prednisone: 60 mg/m2 given orally bid on days 1-5. Patients who achieve CR after 4 cycles enter the consolidation treatment ; Patients with PR after 4 cycles would receive another 2 cycles of R-EPOCH + ibrutinib induction therapy, they could enter the consolidation treatment if they achieve CR ,withdrawn from the study if they achieve = PR; Patients with SD/PD after 4 cycles of treatment are withdrawn from the study. Consolidation: 2 cycles of R-EPOCH + Ibrutinib (dose as before) treatment Maintenance: Ibrutinib 420 mg/day for 24 months or until disease progression or intolerable toxicity

Locations

Country	Name	City	State
China	Peking university Third Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	The second Xiangya hospital of central south university	Changsha	Hunan
China	Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences	Jinan	Shandong
China	The First affiliated hospital of Nanchang University	Nanchang	Jiangxi
China	The First affiliated hospital of China medical university	Shenyang	Liaoning
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The second hospital of Hebei medical university	Shijiazhuang	Hebei
China	Shanxi Cancer Hospital	Taiyuan	Shanxi
China	Tianjin university general hospital	Tianjin	Tianjin
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital	Xian-Janssen Pharmaceutical Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2-year overall survival rate (OS)	Defined as the time interval from enrollment to death of patients in the intent-to-treat population (ITT). If the patient is alive or death of the patient is unknown, the date of death will be the latest time point at which the patient was known to be alive.	2 years
Secondary	Complete response rate (CRR)	Defined as the percentage of subjects who achieved CR after treatment in the per-protocol population as well as in the intent-to-treat population.	1 month after completion of consolidation therapy
Secondary	Overall response rate (ORR)	Defined as the percentage of subjects who achieved CR + PR after treatment in the per-protocol population and the intention-to-treat population.	1 month after completion of consolidation therapy
Secondary	Progression-free survival (PFS)	Defined as the time interval from enrollment to disease progression or death, whichever occurred first, for patients in the intent-to-treat (ITT) population. If there is no progression or time of disease progression is not recorded at the time of withdrawal from the trial, the date of the last examination will be used as the endpoint date.	2 years
Secondary	Minimal residual disease (MRD) negative rate	For patients with bone marrow invasion, on the basis of CR, multicolor flow cytometry detects that tumor cells account for the proportion of nuclear cells, and < 0.01% are MRD negative.	1 month after completion of consolidation therapy
Secondary	Toxic side effects	Non-hematologic toxicity was evaluated according to NCI CTCAE 5.0 criteria; hematologic toxicity was evaluated according to NCI CLL 2018 criteria	3 years