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

NCT ID: NCT02564744

Last Updated: 2024-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-05
• Study Completion Date: 2021-06-25

Brief Summary

The primary purpose of the study was to determine the safety and tolerability, anti-tumor activity of the proposed Debio 1562 dose regimens in combination with rituximab.

Conditions

Diffuse Large B-Cell Lymphoma; B-cell Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Safety Run-in

Participants with a diagnosis of relapsed and/or refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL), and with non-Hodgkin's lymphoma (NHL) including follicular lymphoma (FL), marginal zone lymphoma/mucosa-associated lymphoid tissue (MZL/MALT), mantle cell lymphoma (MCL) or other NHL with the Sponsor's approval received Debio 1562 0.7 mg/kg, intravenous (IV) infusion followed by rituximab 375 mg/m\^2 IV infusion, once on Day 1 of 21-day cycles until the study discontinuation criteria were met (until they develop disease progression, death, unacceptable toxicity, withdraw consent, start new anti-lymphoma treatment or the Sponsor terminates the study).

Group Type: EXPERIMENTAL

Debio 1562

Intervention Type: DRUG

Administered as IV Infusion.

Rituximab

Intervention Type: DRUG

Administered as IV Infusion.

Part 1: Cohort 1

Participants with R/R DLBCL received Debio 1562 0.7 mg/kg, IV infusion followed by rituximab 375 mg/m\^2 IV infusion, once on Day 1 of 21-day cycles until the study discontinuation criteria were met (until they develop disease progression, death, unacceptable toxicity, withdraw consent, start new anti-lymphoma treatment or the Sponsor terminates the study).

Group Type: EXPERIMENTAL

Debio 1562

Intervention Type: DRUG

Administered as IV Infusion.

Rituximab

Intervention Type: DRUG

Administered as IV Infusion.

Part 1: Cohort 2

Participants with R/R, FL, MZL/MALT, MCL or other NHL with the Sponsor's approval received Debio 1562 0.7 mg/kg, IV infusion followed by rituximab 375 mg/m\^2 IV infusion, once on Day 1 of 21-day cycles until the study discontinuation criteria were met (until they develop disease progression, death, unacceptable toxicity, withdraw consent, start new anti-lymphoma treatment or the Sponsor terminates the study).

Group Type: EXPERIMENTAL

Debio 1562

Intervention Type: DRUG

Administered as IV Infusion.

Rituximab

Intervention Type: DRUG

Administered as IV Infusion.

Part 2/3: Cohort A

Participants with relapsed DLBCL received Debio 1562 0.7 mg/kg, IV infusion followed by rituximab 375 mg/m\^2 IV infusion, once on Day 1 of a 21-day cycle for at least 6 cycles and/or until the study discontinuation criteria were met (until they develop disease progression, death, unacceptable toxicity, withdraw consent, start new anti-lymphoma treatment or the Sponsor terminates the study).

Group Type: EXPERIMENTAL

Debio 1562

Intervention Type: DRUG

Administered as IV Infusion.

Rituximab

Intervention Type: DRUG

Administered as IV Infusion.

Part 2/3: Cohort B

Participants with relapsed DLBCL received Debio 1562 0.4 mg/kg IV infusion followed by rituximab 375 mg/m\^2 IV infusion on Day 1, then Debio 1562 0.2 mg/kg IV infusion on Days 8 and 15 of a 21-day cycle for at least 6 cycles and/or until the study discontinuation criteria were met (until they develop disease progression, death, unacceptable toxicity, withdraw consent, start new anti-lymphoma treatment or the Sponsor terminates the study).

Group Type: EXPERIMENTAL

Debio 1562

Intervention Type: DRUG

Administered as IV Infusion.

Rituximab

Intervention Type: DRUG

Administered as IV Infusion.

Interventions

Debio 1562

Administered as IV Infusion.

Intervention Type: DRUG

Rituximab

Administered as IV Infusion.

Intervention Type: DRUG

Eligibility Criteria

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 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Debiopharm International SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Alabama Oncology

Birmingham, Alabama, United States

Carle Foundation Hospital, Cancer Center

Urbana, Illinois, United States

Abbott Northwestern Hospital, Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Novant Health Oncology

Winston-Salem, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Abramson Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, United States

Spartanburg Regional Healthcare System

Spartanburg, South Carolina, United States

Baylor University Medical Center

Dallas, Texas, United States

Swedish Medical Center

Seattle, Washington, United States

CHU UCL Namur asbl - Site Godinne

Yvoir, Namur, Belgium

Jan Yperman Ziekenhuis

Ieper, West-Vlaanderen, Belgium

University Hospitals Leuven, Campus Gasthuisberg

Leuven, , Belgium

St. Augustinus Hospital, Department of Hematology

Wilrijk, , Belgium

University Multiprofile Hospital for Active Treatment "Sveti Georgi"

Plovdiv, , Bulgaria

Specialized Hospital for Active Treatment of Hematological Diseases,Clinic of Hematology

Sofia, , Bulgaria

Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa

Vratsa, , Bulgaria

University Hospital Brno

Brno, , Czechia

University Hospital Hradec Kralove

Hradec Králové, , Czechia

University Hospital Kralovske Vinohrady

Prague, , Czechia

General University Hospital in Prague

Prague, , Czechia

National Institute of Oncology

Budapest, , Hungary

University of Debrecen Clinical Center

Debrecen, , Hungary

Medical Center of the University of Pecs

Pécs, , Hungary

University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona

Ancona, , Italy

Civil Hospital of Brescia

Brescia, , Italy

United Hospitals Villa Sofia Cervello

Palermo, , Italy

Local Healthcare Company 8 Berica (Azienda ULSS8 Berica), Hospital San Bortolo of Vicenza

Vicenza, , Italy

University Clinical Center in Gdansk

Gdansk, , Poland

Provincial Hospitals in Gdynia Sp. z o.o. (LLC)

Gdynia, , Poland

Małopolskie Medical Centre

Krakow, , Poland

St. John of Dukla Oncology Center of Lublin Land

Lublin, , Poland

Regional Hospital of Bellinzona and Valli, Oncology Institute of Southern Switzerland

Bellinzona, Canton Ticino, Switzerland

Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center

Cherkasy, , Ukraine

Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine

Kharkiv, , Ukraine

Communal Non-profit enterprise "Regional Center of Oncology"

Kharkiv, , Ukraine

National Institute of Cancer

Kyiv, , Ukraine

National Research Center for Radiation Medicine

Kyiv, , Ukraine

Kyiv City Clinical Hospital #9, City Hematology Center

Kyiv, , Ukraine

Podillia Regional Oncology Center

Vinnytsia, , Ukraine

Countries

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

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-004061-87

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Debio 1562-201

Identifier Type: -

Identifier Source: org_study_id