Study to Evaluate the Efficacy and Tolerability of Debio 1562 in Combination With Rituximab in Participants With Relapsed and/or Refractory DLBCL and Other Forms of NHL

Diffuse Large B-Cell Lymphoma Clinical Trial

Official title:

A Phase 2 Study to Evaluate the Efficacy and Tolerability of Debio 1562 in Combination With Rituximab in Patients With Relapsed and/or Refractory Diffuse Large B-Cell Lymphoma and Other Forms of Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02564744
• Other study ID #: Debio 1562-201
• Secondary ID: 2015-004061-87
• Status: Completed
• Phase: Phase 2
• Start date: June 15, 2016
• Est. completion date: June 25, 2021

Study information

• Verified date: January 2022
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open label, multicenter, adaptive Phase 2 clinical study. The study will consist of a screening period, a treatment period, an end of treatment visit, and a follow-up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: June 25, 2021
• Est. primary completion date: January 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• For Part 1 of the study, participants must have histopathologically confirmed diagnosis of R/R, DLBCL, FL, MZL/MALT, MCL, or other Sponsor approved NHL subtypes according to the World Health Organization (WHO) classification 2008 for which standard measures do not exist or are no longer effective.
• For Part 2 and Part 3 of the study, participants must have histopathologically and clinically confirmed diagnosis of relapsed DLBCL. Participants will be considered to have a relapsed disease if they showed a duration of response of at least 24 weeks after their first line of therapy. The following participants with relapsed DLBCL will

be enrolled:

1. Participants who received at least only one line of previous therapy and achieved either complete response (CR) or partial response (PR) for at least 24 weeks (from the last day of the last cycle) after their first line of therapy, but are not eligible for high dose chemotherapy with autologous stem cell transplantation (HD-ASCT)

2. Participants who received more than one line of previous therapy (including HD-ASCT), and have achieved a duration of response (CR or PR) of at least 8 weeks (from the last day of the last cycle) after their last line of therapy

• Participants must have evaluable or measurable disease in accordance with the International Working Group Guidelines for Lymphoma.
• Participants must have received at least one but no more than six prior treatment regimens. Prior treatment with an anti-cluster of differentiation 20 (anti-CD20) agent, either alone or in combination, is allowed.
• Participants must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0
• 2.
• Participants who are Hepatitis B surface antigen positive (HBsAg+) (must be polymerase chain reaction (PCR) negative) who are taking antivirals, are allowed to enroll.

Exclusion Criteria:

• Participants with a diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• For Part 2 and Part 3 of the study, participants with primary refractory DLBCL (defined as progression of disease within 24 weeks after first line of treatment).
• For Part 2 and Part 3 of the study, participants that are eligible to undergo first time HD-ASCT.
• For Part 2 and Part 3 of the study, participants with R/R FL, MZL/MALT, MCL, or any other NHL subtypes according to the WHO classification.
• Participants with active hepatitis A, B or C infection.
• Women who are pregnant or breast feeding.
• Participants who have received prior therapy with other anti-CD37-targeting therapy.
• Participants who have known central nervous system, meningeal, or epidural disease including brain metastases.
• Participants with impaired cardiac function or clinically significant cardiac disease.
• Participants currently presenting interstitial lung disease, diffuse parenchymal lung disease, or with a past history of severe/Grade 3 parenchymal lung disorders.

Related Conditions & MeSH terms

• B-cell Non-Hodgkin's Lymphoma
• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Debio 1562
Safety run in: Debio 1562 will be given on the same day as rituximab, once every three weeks (Q3W) intravenously (IV) at the dose of 0.7 mg/kg on Day 1 of a 21-day cycle. Parts 2 and 3: Cohort A- Debio 1562 will be given on the same day as rituximab, once every three weeks (Q3W) intravenously (IV) at the dose of 0.7 mg/kg on Day 1 of a 21-day cycle. Cohort B- Debio 1562 weekly (QW) will be given at a total dose of 0.8 milligram per kilogram (mg/kg) IV over a 21-day cycle. Participants receiving QW regimen will be allowed to switch to Q3W regimen during Coronavirus Disease 2019 (COVID-19) pandemic.
• Rituximab
Rituximab will be given on the same day as Debio 1562, Q3W IV at a dose of 375 mg/m^2 on Day 1 of a 21-day cycle in all participants.

Locations

Country	Name	City	State
Belgium	Jan Yperman Ziekenhuis	Ieper	West-Vlaanderen
Belgium	University Hospitals Leuven, Campus Gasthuisberg, Department of Medical Oncology	Leuven
Belgium	St. Augustinus Hospital, Department of Hematology	Wilrijk
Belgium	CHU UCL Namur asbl - Site Godinne	Yvoir	Namur
Bulgaria	University Multiprofile Hospital for Active Treatment "Sveti Georgi", Clinic of Medical Oncology	Plovdiv
Bulgaria	Specialized Hospital for Active Treatment of Hematological Diseases,Clinic of Hematology, Department of Clinical Hematology	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa, First Department of Internal Medicine	Vratsa
Czechia	University Hospital Brno	Brno
Czechia	University Hospital Hradec Kralove	Hradec Králové
Czechia	General University Hospital in Prague	Prague
Czechia	University Hospital Kralovske Vinohrady	Prague
Hungary	National Institute of Oncology	Budapest
Hungary	University of Debrecen Clinical Center	Debrecen
Hungary	Medical Center of the University of Pecs	Pécs
Italy	University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona, Clinic of Hematology	Ancona
Italy	Civil Hospital of Brescia	Brescia
Italy	United Hospitals Villa Sofia Cervello, Department of Hematology and Oncology	Palermo
Italy	Local Healthcare Company 8 Berica (Azienda ULSS8 Berica), Hospital San Bortolo of Vicenza, Complex Operative Unit of Hematology	Vicenza
Poland	University Clinical Center in Gdansk, Teaching Department of Hematology and Transplantology	Gdansk
Poland	Malopolskie Medical Centre	Kraków
Poland	St. John of Dukla Oncology Center of Lublin Land, Department of Hematology	Lublin
Poland	Provincial Hospitals in Gdynia Sp. z o.o. (LLC), Department of Oncology and Radiotherapy, Clinical Oncology Unit	Olsztyn
Switzerland	Oncology Institute of Southern Switzerland - Ospedale Regionale Bellinzona e Valli	Bellinzona	Ticino
Ukraine	Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center, Department of Hematology	Cherkasy
Ukraine	Communal Non-profit enterprise "Regional Center of Oncology"	Kharkiv
Ukraine	S.P. Hryhoriev Institute of Medical Radiology	Kharkiv
Ukraine	Kyiv City Clinical Hospital #9, City Hematology Center	Kyiv
Ukraine	National Institute of Cancer	Kyiv
Ukraine	National Research Center for Radiation Medicine	Kyiv
Ukraine	Podillia Regional Oncology Center	Vinnytsia
United States	Alabama Oncology	Birmingham	Alabama
United States	Cleveland Clinic	Cleveland	Ohio
United States	Baylor Sammons Cancer Center	Dallas	Texas
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Abramson Cancer Center of The University of Pennsylvania	Philadelphia	Pennsylvania
United States	Swedish Medical Center	Seattle	Washington
United States	Spartanburg Regional Healthcare System	Spartanburg	South Carolina
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	Novant Health Oncology	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Czechia,  Hungary,  Italy,  Poland,  Switzerland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		up to 30 months
Primary	Objective Response Rate (ORR)	Number of participants with clinical responses as assessed by Lugano Classification of response assessments.	up to 30 months
Secondary	Maximum plasma drug concentration (Cmax) of Debio 1562 and Rituximab		Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6
Secondary	Area under the time-concentration curve from time 0 to t (AUC0-t) of Debio 1562 and Rituximab		Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6
Secondary	Area under the time-concentration curve from time 0 to infinity (AUC0-inf) of Debio 1562 and Rituximab		Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6
Secondary	Terminal half-life (t1/2) of Debio 1562 and Rituximab		Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6
Secondary	Clearance (CL) of Debio 1562 and Rituximab		Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6
Secondary	Volume of Distribution at Steady State (Vss) of Debio 1562 and Rituximab		Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6
Secondary	Time to Maximum Plasma Concentration (Tmax) of Debio 1562 and Rituximab		Part 1: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15, Cycles 1 and 3 (each cycle=21 days); Day 1 Cycles 2, 4-8; Parts 2 and 3: Pre-dose, within 5 minutes of infusion, on Days 1, 2, 3, 8, 15 for Cycles 1-2; Days 1, 8, 15 for Cycles 3-6
Secondary	Progression-free survival (PFS)		up to 30 months
Secondary	Time to response		up to 30 months
Secondary	Duration of response (DOR)		up to 30 months
Secondary	Overall survival (OS)		up to 30 months
Secondary	Number of participants with presence of human anti-drug antibody (ADA) for Debio 1562		Part 1: Pre-dose on Day 1 of Cycles 1-8 (each cycle=21 days); Parts 2 and 3: Pre-dose on Day 1 of Cycles 1-6; and at the end of treatment (Up to Month 36) and 30-day follow-up visit or Day 1 Cycle 7 for participants who received treatment beyond Cycle 6