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 5, 2016
• Est. completion date: June 25, 2021

Study information

• Verified date: May 2024
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 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
Administered as IV Infusion.
• Rituximab
Administered as IV Infusion.

Locations

Country	Name	City	State
Belgium	Jan Yperman Ziekenhuis	Ieper	West-Vlaanderen
Belgium	University Hospitals Leuven, Campus Gasthuisberg	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"	Plovdiv
Bulgaria	Specialized Hospital for Active Treatment of Hematological Diseases,Clinic of Hematology	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa	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	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
Poland	University Clinical Center in Gdansk	Gdansk
Poland	Provincial Hospitals in Gdynia Sp. z o.o. (LLC)	Gdynia
Poland	Malopolskie Medical Centre	Kraków
Poland	St. John of Dukla Oncology Center of Lublin Land	Lublin
Switzerland	Regional Hospital of Bellinzona and Valli, Oncology Institute of Southern Switzerland	Bellinzona	Ticino
Ukraine	Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center	Cherkasy
Ukraine	Communal Non-profit enterprise "Regional Center of Oncology"	Kharkiv
Ukraine	Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine	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 University Medical Center	Dallas	Texas
United States	Abbott Northwestern Hospital, 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 Foundation Hospital, Cancer Center	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 (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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Volume of Distribution at Steady State (Vss) 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
Secondary	Time to Maximum Plasma Concentration (Tmax) 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
Secondary	Progression-free Survival (PFS)	PFS was defined as the duration between the first dose date of Debio 1562 and the date of progressive disease (PD) or death due to any cause, whichever occurs first. PD is defined as the new or clear progression of preexisting non-measured lesions or regrowth of previously resolved lesions or a new node >1.5 cm in any axis or an abnormal lesion with >1.5 cm longest transverse diameter or increase by >50% of lesion.	Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first
Secondary	Time to Response (TTR)	TTR was defined as the duration between the first dose date of Debio 1562 and the date of first objective response (PR or CR). 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 PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first
Secondary	Duration of Response (DOR)	DOR was defined as duration between date of the first objective response (PR or CR) and date of PD or death due to any cause, whichever occurs first. CR: 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: =50% decrease in sum of diameters of up to 6 target measurable nodes or extranodal sites, no new lesions formation. PD: New or clear progression of preexisting non-measured lesions or regrowth of previously resolved lesions or a new node >1.5 cm in any axis or an abnormal lesion with >1.5 cm longest transverse diameter or increase by >50% of lesion.	Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first
Secondary	Overall Survival (OS)	OS was defined as the duration between the first dose date of Debio 1562 and the date of death due to any cause.	Up to death or end of study (approximately 57 months) or one year from the last participant's first dose
Secondary	Number of Participants With Anti-drug Antibodies (ADA) for Debio 1562	The potential immunogenicity against Debio 1562 was assessed in an ADA population.	Part 1: Pre-dose on Day 1 of Cycle(C)1 to 8; Part 2/3: Pre-dose on Day 1 of C1 to 6 and on Day 1 of C7 for participants who received treatment beyond C6 (each C=21 days); Parts 1, 2/3: Month 37 (EOT) and Month 38 (30-Day FU visit) (Cycle=21 days)