Study to Evaluate the Efficacy and Tolerability of Debio... | NCT02564744

ID	Type	Description	Link
2015-004061-87	EudraCT Number

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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

Facility	Status	City	State	ZIP	Country	Contacts
Alabama Oncology		Birmingham	Alabama	35211	United States
Carle Foundation Hospital, Cancer Center

ID	Title	Description
FG000	Part 1: Safety Run-in	Participants with a diagnosis of R/R DLBCL, and with 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).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 11, 2020	Nov 16, 2023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

Safety population included all participants from the screened population who received at least one dose of Debio 1562.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Part 1: Safety Run-in	Participants with a diagnosis of R/R DLBCL, and with NHL including 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).
OG001	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).
OG002	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).
OG003	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).
OG004	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).

Units	Counts
Participants	OG00017 OG0018 OG00212 OG003

Title

Denominators

Categories

Title	Measurements
	OG00016 OG0018 OG00212 OG003

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).

Safety population includes all participants from the screened population who received at least one dose of Debio 1562.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Part 1: Safety Run-in	Participants with a diagnosis of R/R DLBCL, and with NHL including 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).

Primary

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

A standard 12-lead ECG was performed.

Safety population included all participants from the screened population who received at least one dose of Debio 1562.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Part 1: Safety Run-in	Participants with a diagnosis of R/R DLBCL, and with NHL including 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).
OG001	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).
OG002	Part 1: Cohort 2

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.

Safety population included all participants from the screened population who received at least one dose of Debio 1562.

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	Part 1: Safety Run-in	Participants with a diagnosis of R/R DLBCL, and with NHL including 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).
OG001	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).
OG002

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.

EE population included all participants who received at least one dose of Debio 1562 and rituximab and had both baseline and post-baseline evaluable disease assessments (including clinical PD).

Posted

Number

95% Confidence Interval

percent responders

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

ID	Title	Description
OG000	Part 1: Safety Run-in	Participants with a diagnosis of R/R DLBCL, and with NHL including 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).
OG001

Secondary

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

PK population included all participants who received at least one dose of Debio 1562 or rituximab and had atleast one PK concentration result available. Number analyzed signifies the number of participants with available data at the specific timepoint.

Posted

Mean

Standard Deviation

nanogram per milliliter (ng/ml)

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)

ID	Title	Description
OG000	Part 1: Safety Run-in	Participants with a diagnosis of R/R DLBCL, and with NHL including 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).
OG001	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).

Secondary

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