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

NCT02564744 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: Debio 1562-2012015-004061-87
• Study Type: interventional
• Target: 100
• Locations: 9 countries
• Sites: 39

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

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  An AE was defined as any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered study drug related. This included exacerbation of a pre-existing condition. AEs included worsening (change in nature, severity, or frequency) of conditions present at the onset of the study, intercurrent illnesses, drug interactions, events related to or possibly related to concomitant medications, abnormal laboratory values (this included significant shifts from baseline within the range of normal that the Investigator considered to be clinically important), clinically significant abnormalities in physical examination, vital signs, and weight.

  Up to 30 days after end of treatment (EOT) (Up to 38 months)

• Number of Participants With Clinically Significant Changes in Clinical Laboratory Test Results Reported as TEAEs

  The clinical laboratory tests included Hematology: Hematocrit (Hct), hemoglobin (Hgb), platelet count, red blood cell (RBC) count, white blood cell (WBC) count with differential; Serum Chemistry: Albumin (ALB), alkaline phosphatase (ALK-P), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), calcium (Ca), chloride (Cl), creatinine, glucose, lactate dehydrogenase (LDH), magnesium, phosphorus, potassium (K), sodium (Na), total bilirubin, total protein, uric acid, immunoglobulin levels (IgG, IgA, IgM); Urinalysis: Appearance, specific gravity and pH, evaluation of glucose, protein, bilirubin, ketones, leukocytes and blood; Coagulation: Prothrombin time (PT) or international normalized ratio (INR), activated partial thromboplastin time (aPTT).

  Up to 30 days after EOT (Up to 38 months)

• Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs

  A standard 12-lead ECG was performed.

  Up to 30 days after EOT (Up to 38 months)

• Number of Participants With Clinically Significant Changes in Vital Sign Measurements Reported as TEAEs

  Vital signs included systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate.

  Up to 30 days after EOT (Up to 38 months)

• Objective Response Rate (ORR)

  ORR was defined as the percentage of participants with a Best overall response (BOR) of partial response (PR) or complete response (CR). BOR was the best response recorded from the start of the treatment until disease progression, initiation of new anti-cancer therapy, or end of the study period, whichever occurred first. CR was defined as disappearance of all target lesions, no new lesions formation. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to ≤1.5 cm. PR was defined as ≥50% decrease in the sum of diameters of up to 6 target measurable nodes or extranodal sites, no new lesions formation.

  Up to Progressive Disease (PD) or death (up to approximately 55 months) or initiation of new anti-cancer therapy whichever occurs first

Secondary Outcomes (12)

• Maximum Plasma Drug Concentration (Cmax) of Debio 1562 and Rituximab

  Parts 1, 2/3: Pre and Post infusion: 5 min-Day (D) 1 of Cycles (C) 1-8 and 2 hours (h)-D1 of C1-2 (for Part 2/3), 24h-D2, 48h-D3 and D8, 15 of C1, 2; D1 of Month 37 (EOT) (rituximab only) and Month 38 (follow-up) (Cycle=21 days)

• Area Under the Time-concentration Curve From Time 0 to t (AUC0-t) of Debio 1562 and Rituximab

  Parts 1, 2/3: Pre-dose, post infusion-5 min on Day 1 of C 1-6, 5 min on Day 1 of C 7, 8 and 2 h on Day 1 of C 1, 2 (only for Part 2/3), 24 h on Day 2, 48 h on Day 3, Days 8 and 15 of C 1, 2 (Cycle=21 days); EOT (up to 37 months), 30-day follow up

• Area Under the Time-concentration Curve From Time 0 to Infinity (AUC0-inf) of Debio 1562 and Rituximab

  Parts 1, 2/3: Pre-dose, post infusion-5 min on Day 1 of C 1-6, 5 min on Day 1 of C 7, 8 and 2 h on Day 1 of C 1, 2 (only for Part 2/3), 24 h on Day 2, 48 h on Day 3, Days 8 and 15 of C 1, 2 (Cycle=21 days); EOT (up to 37 months), 30-day follow up

• Terminal Half-life (t1/2) of Debio 1562 and Rituximab

  Parts 1, 2/3: Pre-dose, post infusion-5 min on Day 1 of C 1-6, 5 min on Day 1 of C 7, 8 and 2 h on Day 1 of C 1, 2 (only for Part 2/3), 24 h on Day 2, 48 h on Day 3, Days 8 and 15 of C 1, 2 (Cycle=21 days); EOT (up to 37 months), 30-day follow up

• Clearance (CL) of Debio 1562 and Rituximab

  Parts 1, 2/3: Pre-dose, post infusion-5 min on Day 1 of C 1-6, 5 min on Day 1 of C 7, 8 and 2 h on Day 1 of C 1, 2 (only for Part 2/3), 24 h on Day 2, 48 h on Day 3, Days 8 and 15 of C 1, 2 (Cycle=21 days); EOT (up to 37 months), 30-day follow up

Study Arms (5)

Part 1: Safety Run-in

EXPERIMENTAL

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).

Drug: Debio 1562; Drug: Rituximab

Part 1: Cohort 1

EXPERIMENTAL

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).

Drug: Debio 1562; Drug: Rituximab

Part 1: Cohort 2

EXPERIMENTAL

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).

Drug: Debio 1562; Drug: Rituximab

Part 2/3: Cohort A

EXPERIMENTAL

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).

Drug: Debio 1562; Drug: Rituximab

Part 2/3: Cohort B

EXPERIMENTAL

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).

Drug: Debio 1562; Drug: Rituximab

Interventions

Debio 1562 DRUG

Administered as IV Infusion.

Part 1: Cohort 1; Part 1: Cohort 2; Part 1: Safety Run-in; Part 2/3: Cohort A; Part 2/3: Cohort B

Rituximab DRUG

Administered as IV Infusion.

Part 1: Cohort 1; Part 1: Cohort 2; Part 1: Safety Run-in; Part 2/3: Cohort A; Part 2/3: Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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)
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (39)

Alabama Oncology

Birmingham, Alabama, 35211, United States

Location

Carle Foundation Hospital, Cancer Center

Urbana, Illinois, 61801, United States

Location

Abbott Northwestern Hospital, Virginia Piper Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

Novant Health Oncology

Winston-Salem, North Carolina, 27103, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Abramson Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Spartanburg Regional Healthcare System

Spartanburg, South Carolina, 29303, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Swedish Medical Center

Seattle, Washington, 98104, United States

Location

CHU UCL Namur asbl - Site Godinne

Yvoir, Namur, 5530, Belgium

Location

Jan Yperman Ziekenhuis

Ieper, West-Vlaanderen, 8900, Belgium

Location

University Hospitals Leuven, Campus Gasthuisberg

Leuven, 3000, Belgium

Location

St. Augustinus Hospital, Department of Hematology

Wilrijk, 2610, Belgium

Location

University Multiprofile Hospital for Active Treatment "Sveti Georgi"

Plovdiv, 4002, Bulgaria

Location

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

Sofia, 1756, Bulgaria

Location

Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa

Vratsa, 3000, Bulgaria

Location

University Hospital Brno

Brno, 625 00, Czechia

Location

University Hospital Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

University Hospital Kralovske Vinohrady

Prague, 100 34, Czechia

Location

General University Hospital in Prague

Prague, 128 08, Czechia

Location

National Institute of Oncology

Budapest, H-1122, Hungary

Location

University of Debrecen Clinical Center

Debrecen, 4032, Hungary

Location

Medical Center of the University of Pecs

Pécs, H-7624, Hungary

Location

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

Ancona, 60126, Italy

Location

Civil Hospital of Brescia

Brescia, 25123, Italy

Location

United Hospitals Villa Sofia Cervello

Palermo, 90146, Italy

Location

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

Vicenza, 36100, Italy

Location

University Clinical Center in Gdansk

Gdansk, 80-214, Poland

Location

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

Gdynia, 81-519, Poland

Location

Małopolskie Medical Centre

Krakow, 30-510, Poland

Location

St. John of Dukla Oncology Center of Lublin Land

Lublin, 20-090, Poland

Location

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

Bellinzona, Canton Ticino, 6500, Switzerland

Location

Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center

Cherkasy, 18009, Ukraine

Location

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

Kharkiv, 61024, Ukraine

Location

Communal Non-profit enterprise "Regional Center of Oncology"

Kharkiv, 61070, Ukraine

Location

National Institute of Cancer

Kyiv, 03022, Ukraine

Location

National Research Center for Radiation Medicine

Kyiv, 03115, Ukraine

Location

Kyiv City Clinical Hospital #9, City Hematology Center

Kyiv, 04112, Ukraine

Location

Podillia Regional Oncology Center

Vinnytsia, 21029, Ukraine

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Vice President Clinical Research & Development
• Organization: Debiopharm International S.A.

info-international@debiopharm.com

4121 321 01 11

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The interventional study model is sequential for Part 1 and Part 2/3 of the study, and parallel for Cohorts 1 and 2 of Part 1, and for Cohorts A and B of Part 2/3.

Study Record Dates

• First Submitted: September 11, 2015
• First Posted: October 1, 2015
• Study Start: June 5, 2016
• Primary Completion: January 13, 2021
• Study Completion: June 25, 2021
• Last Updated: June 12, 2024
• Results First Posted: May 17, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (4); US (9); CH (1); UA (7); HU (3); CZ (4); PL (4); BU (3); IT (4)