Clinical Trials /

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

NCT02564744

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Non-Hodgkin Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate the Efficacy and Tolerability Debio 1562 in Combination With Rituximab in Patients With Relapsed and/or Refractory DLBCL and Other Forms of NHL
  • 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 IDs

  • ORG STUDY ID: Debio 1562-201
  • SECONDARY ID: 2015-004061-87
  • NCT ID: NCT02564744

Conditions

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

Interventions

DrugSynonymsArms
Debio 1562Debio 1562
RituximabDebio 1562

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Debio 1562ExperimentalParticipants with a diagnosis of relapsed and/or refractory (R/R) Diffuse Large B Cell Lymphoma (DLBCL), Follicular Non-Hodgkin's Lymphoma (FL), Marginal Zone/Mucosa-associated Lymphoid Tissue (MZ/MALT), Mantle Cell Lymphoma (MCL) or other Non-Hodgkin's Lymphoma (NHL) with the Sponsor's approval, will receive Debio 1562 and Rituximab in 3 different parts of study i.e., Safety run in, Part 2 and Expansion (Part 3). Participants in Part 2 will be enrolled in two parallel cohorts (Cohort A and Cohort B).
  • Debio 1562
  • Rituximab

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 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-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 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, patients 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame:up to 30 months
Safety Issue:
Description:Number of participants with clinical responses as assessed by Lugano Classification of response assessments.

Secondary Outcome Measures

Measure:Maximum plasma drug concentration (Cmax) of Debio 1562 and Rituximab
Time Frame:Part 1: Pre-dose and within 5 minutes of infusion, on Day 1, 2, 3, 8, 15 for Cycles 1 and 3; and on Day 1 for Cycles 2, 4-8; Part 2: Pre-dose and within 5 minutes of infusion, Day 1, 2, 3, 8, 15 for Cycles 1-2; Day 1, 8, 15 for Cycles 3-6
Safety Issue:
Description:
Measure:Area under the time-concentration curve from time 0 to t (AUC0-t) of Debio 1562 and Rituximab
Time Frame:Part 1: Pre-dose and within 5 minutes of infusion, on Day 1, 2, 3, 8, 15 for Cycles 1 and 3; and on Day 1 for Cycles 2, 4-8; Part 2: Pre-dose and within 5 minutes of infusion, Day 1, 2, 3, 8, 15 for Cycles 1-2; Day 1, 8, 15 for Cycles 3-6
Safety Issue:
Description:
Measure:Area under the time-concentration curve from time 0 to infinity (AUC0-inf) of Debio 1562 and Rituximab
Time Frame:Part 1: Pre-dose and within 5 minutes of infusion, on Day 1, 2, 3, 8, 15 for Cycles 1 and 3; and on Day 1 for Cycles 2, 4-8; Part 2: Pre-dose and within 5 minutes of infusion, Day 1, 2, 3, 8, 15 for Cycles 1-2; Day 1, 8, 15 for Cycles 3-6
Safety Issue:
Description:
Measure:Terminal half-life (t1/2) of Debio 1562 and Rituximab
Time Frame:Part 1: Pre-dose and within 5 minutes of infusion, on Day 1, 2, 3, 8, 15 for Cycles 1 and 3; and on Day 1 for Cycles 2, 4-8; Part 2: Pre-dose and within 5 minutes of infusion, Day 1, 2, 3, 8, 15 for Cycles 1-2; Day 1, 8, 15 for Cycles 3-6
Safety Issue:
Description:
Measure:Clearance (CL) of Debio 1562 and Rituximab
Time Frame:Part 1: Pre-dose and within 5 minutes of infusion, on Day 1, 2, 3, 8, 15 for Cycles 1 and 3; and on Day 1 for Cycles 2, 4-8; Part 2: Pre-dose and within 5 minutes of infusion, Day 1, 2, 3, 8, 15 for Cycles 1-2; Day 1, 8, 15 for Cycles 3-6
Safety Issue:
Description:
Measure:Volume of Distribution at Steady State (Vss) of Debio 1562 and Rituximab
Time Frame:Part 1: Pre-dose and within 5 minutes of infusion, on Day 1, 2, 3, 8, 15 for Cycles 1 and 3; and on Day 1 for Cycles 2, 4-8; Part 2: Pre-dose and within 5 minutes of infusion, Day 1, 2, 3, 8, 15 for Cycles 1-2; Day 1, 8, 15 for Cycles 3-6
Safety Issue:
Description:
Measure:Time to Maximum Plasma Concentration (Tmax) of Debio 1562 and Rituximab
Time Frame:Part 1: Pre-dose and within 5 minutes of infusion, on Day 1, 2, 3, 8, 15 for Cycles 1 and 3; and on Day 1 for Cycles 2, 4-8; Part 2: Pre-dose and within 5 minutes of infusion, Day 1, 2, 3, 8, 15 for Cycles 1-2; Day 1, 8, 15 for Cycles 3-6
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:up to 30 months
Safety Issue:
Description:
Measure:Time to response
Time Frame:up to 30 months
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:up to 30 months
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:up to 30 months
Safety Issue:
Description:
Measure:Number of participants with presence of human anti-drug antibody (ADA) for Debio 1562
Time Frame:Pre-dose on Day 1 of Cycles 1 to 8; and at the end of treatment (Up to Month 36) and 30-day follow-up visit
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Debiopharm International SA

Last Updated

April 1, 2021