Phase III Study of SyB L-0501 in Combination With Rituximab to Treat Recurrent/Relapsed Diffuse Large B-Cell Lymphoma

• ClinicalTrials.gov Identifier: NCT03372837
• Recruitment Status: Completed
• First Posted: December 14, 2017
• Last Update Posted: April 18, 2023
• Sponsor: SymBio Pharmaceuticals
• Information provided by (Responsible Party): SymBio Pharmaceuticals

Tracking Information

• First Submitted Date: December 10, 2017
• First Posted Date: December 14, 2017
• Last Update Posted Date: April 18, 2023
• Actual Study Start Date: January 15, 2018
• Actual Primary Completion Date: December 31, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 10, 2017)

Overall Response Rate [ Time Frame: up to 30 weeks ]

Complete Response (CR) + Partial Response (PR) Determined on the Basis of Revised Response Criteria for Malignant Lymphoma (Revised RC 2007)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 18, 2018)

• Complete Response (CR) Rate [ Time Frame: up to 30 weeks ]
  Determined on the Basis of Revised Response Criteria for Malignant Lymphoma (Revised RC 2007)
• Progression Free Survival (PFS) [ Time Frame: up to 30 weeks ]
  PFS = day of the first PFS event - day of start of study treatment + 1
• Duration of Response (DOR) [ Time Frame: up to 30 weeks ]
  DOR is the period from the date of achieving CR, or PR in the responders to the earliest onset date of any progression events calculated using the Kaplan-Meier estimator. The median and the 95% Confidence Interval (CI ) were calculated using Greenwood's formula.
• Overall Survival (OS) [ Time Frame: up to 30 weeks. ]
  Death due to any given cause was defined as an event. OS was calculated using the Kaplan-Meier estimator. The median and the 95% CI were calculated using Greenwood's formula.

Original Secondary Outcome Measures (submitted: December 10, 2017)

• Complete Response (CR) Rate [ Time Frame: up to 30 weeks ]
  Determined on the Basis of Revised Response Criteria for Malignant Lymphoma (Revised RC 2007)
• Progression Free Survival (PFS) [ Time Frame: up to 30 weeks ]
  PFS = day of the first PFS event - day of start of study treatment + 1
• Duration of Response (DOR) [ Time Frame: up to 30 weeks ]
  DOR is the period from the date of achieving CR, CRu or PR in the responders to the earliest onset date of any progression events calculated using the Kaplan-Meier estimator. The median and the 95% CI were calculated using Greenwood's formula.
• Overall Survival (OS) [ Time Frame: up to 30 weeks. ]
  Death due to any given cause was defined as an event. OS was calculated using the Kaplan-Meier estimator. The median and the 95% CI were calculated using Greenwood's formula.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase III Study of SyB L-0501 in Combination With Rituximab to Treat Recurrent/Relapsed Diffuse Large B-Cell Lymphoma
• Official Title: A Multicenter, Open-label Phase III Study of SyB L-0501 in Combination With Rituximab in Patients With Recurrent or Relapsed Diffuse Large B-Cell Lymphoma
• Brief Summary: The purpose of this study is to determine the efficacy of SyB L-0501 in combination with rituximab in patients with recurrent/relapsed diffuse large B-cell lymphoma.
• Detailed Description: Primary Objective is to determine the efficacy, as measured by overall response rate on the basis of Revised Response Criteria for Malignant Lymphoma, of SyB L-0501 at 120 mg/m^2/day on Day 2 and Day 3 in combination with rituximab at 375 mg/m^2 on Day 1 of each 21-day cycle in patients with recurrent/relapsed diffuse large B-cell lymphoma.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Assess the Efficacy and Safety of SyB L-0501 in Combination With Rituximab in Patients With Recurrent or Relapsed DLBCL

Intervention

Drug: Rituximab

The administration of rituximab at 375 mg/m^2/day by intravenous infusion on Day 1 of each 21-day cycle with up to 6 cycles. Dose modifications are not permitted.

Study Arms

Experimental: SyB L-0501

The administration of SyB L-0501 at 120 mg/m^2/day by intravenous infusion on Day 2 and Day 3 of each 21-day cycle with up to 6 cycles. Dose modifications are permitted from 2nd cycle according to dose reduction schedule.

SyB L-0501 60 mg/m^2, 90 mg/m^2 or 120 mg/m^2/day on Day 2 and Day 3 will be followed by 18 days of observation.

Intervention: Drug: Rituximab

• Publications *: Murayama K, Kiguchi T, Izutsu K, Kameoka Y, Hidaka M, Kato H, Rai S, Kuroda J, Ishizawa K, Ichikawa S, Ando K, Ogura M, Fukushima K, Terui Y. Bendamustine plus rituximab in Japanese patients with relapsed or refractory diffuse large B-cell lymphoma. Ann Hematol. 2022 May;101(5):979-989. doi: 10.1007/s00277-022-04801-2. Epub 2022 Mar 4.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 25, 2019): 40
• Original Estimated Enrollment (submitted: December 10, 2017): 60
• Actual Study Completion Date: December 31, 2019
• Actual Primary Completion Date: December 31, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria Patients who satisfy all of the conditions listed below.

1. Patients with histopathologically confirmed diffuse large B-cell lymphoma (DLBCL) except for transformed lymphoma on the basis of World Health Organization (WHO) histological classification (4th ed., 2008).
2. Patients with documented Cluster of differentiation 20 (CD20)-positive for lymphoma cells.
3. Patient with recurrent or relapsed DLBCL after R-CHOP-like theraphy as the firstline therapy.
4. Patients with measurable lesions >1.5 cm in major axes.
5. Patients who are expected to survive for at least 3 months.
6. Patients aged 20 or above at the time informed consent is obtained.
7. Patient with Performance Status (P.S.) 0-1.
8. Patients with adequately maintained organ function.

Exclusion Criteria The study subject should be excluded if any one of the following condition exists.

1. Patients who have been without treatment for less than 3 weeks after prior treatment.
2. Patients who can be candidates for autologous peripheral blood stem cell transplantation at the discretion of the investigator.
3. Patients who received adequate prior treatments and did not respond to any of them.
4. Patient who received prior chemotherapy 3 regimens or more.
5. Patients with central nervous system (CNS) involvement or patients with clinical symptoms suggestive of CNS involvement.
6. Patient with serious active infection.
7. Patient with serious complication.
8. Patient with complication or medical history of serious cardiac disease.
9. Patient with serious gastrointestinal symptoms.
10. Patient with malignant pleural effusion, pericardial effusion, or ascites retention.
11. Patients positive for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody, or HIV antibody.
12. Patient with serious bleeding tendency.
13. Patient with a fever of 38.0°C or higher.
14. Patients with, or confirmed in the past to have had, interstitial pneumonia, pulmonary fibrosis, or pulmonary emphysema.
15. Patients with active multiple primary cancer or patients with a history of other malignant cancer within the past 5 years, except for basal cell cancer of the skin, squamous cell cancer, or cervical cancer in situ.
16. Patients with, or confirmed in the past to have had, autoimmune hemolytic anemia.
17. Patient who received bendamustin hydrochloride in the past.
18. Patients who received cytokine preparation such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) or blood transfusions within 2 weeks before the examination at registration for this study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT03372837
• Other Study ID Numbers: 2017002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: SymBio Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: SymBio Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: SymBio Pharmaceuticals
• Verification Date: June 2022