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
- Conditions
- B-cell Non-Hodgkin's LymphomaDiffuse Large B-Cell Lymphoma
- Interventions
- Registration Number
- NCT02564744
- Lead Sponsor
- Debiopharm International SA
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 100
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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.
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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
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Participants must have evaluable or measurable disease in accordance with the International Working Group Guidelines for Lymphoma.
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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.
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Participants must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2.
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Participants who are Hepatitis B surface antigen positive (HBsAg+) (must be polymerase chain reaction (PCR) negative) who are taking antivirals, are allowed to enroll.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1: Cohort 1 Debio 1562 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). Part 1: Cohort 2 Debio 1562 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). Part 1: Safety Run-in Debio 1562 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). Part 2/3: Cohort B Debio 1562 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). Part 2/3: Cohort A Debio 1562 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). Part 1: Safety Run-in Rituximab 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). Part 1: Cohort 1 Rituximab 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). Part 1: Cohort 2 Rituximab 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). Part 2/3: Cohort A Rituximab 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). Part 2/3: Cohort B Rituximab 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).
- Primary Outcome Measures
Name Time Method Number of Participants With Clinically Significant Changes in Clinical Laboratory Test Results Reported as TEAEs Up to 30 days after EOT (Up to 38 months) 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).
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs Up to 30 days after EOT (Up to 38 months) A standard 12-lead ECG was performed.
Number of Participants With Clinically Significant Changes in Vital Sign Measurements Reported as TEAEs Up to 30 days after EOT (Up to 38 months) Vital signs included systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate.
Objective Response Rate (ORR) Up to Progressive Disease (PD) or death (up to approximately 55 months) or initiation of new anti-cancer therapy whichever occurs first 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Up to 30 days after end of treatment (EOT) (Up to 38 months) 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.
- Secondary Outcome Measures
Name Time Method 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 Time to Response (TTR) Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first 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.
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 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 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 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 Overall Survival (OS) Up to death or end of study (approximately 57 months) or one year from the last participant's first dose OS was defined as the duration between the first dose date of Debio 1562 and the date of death due to any cause.
Duration of Response (DOR) Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first 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.
Number of Participants With Anti-drug Antibodies (ADA) for Debio 1562 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) The potential immunogenicity against Debio 1562 was assessed in an ADA population.
Progression-free Survival (PFS) Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first 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.
Trial Locations
- Locations (39)
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Abramson Cancer Center of The University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
National Institute of Cancer
🇺🇦Kyiv, Ukraine
CHU UCL Namur asbl - Site Godinne
🇧🇪Yvoir, Namur, 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
Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center
🇺🇦Cherkasy, Ukraine
University Hospitals Leuven, Campus Gasthuisberg
🇧🇪Leuven, Belgium
University Clinical Center in Gdansk
🇵🇱Gdańsk, Poland
Spartanburg Regional Healthcare System
🇺🇸Spartanburg, South Carolina, United States
Jan Yperman Ziekenhuis
🇧🇪Ieper, West-Vlaanderen, Belgium
Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa
🇧🇬Vratsa, Bulgaria
Medical Center of the University of Pecs
🇭🇺Pécs, Hungary
Communal Non-profit enterprise "Regional Center of Oncology"
🇺🇦Kharkiv, Ukraine
Małopolskie Medical Centre
🇵🇱Kraków, Poland
Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine
🇺🇦Kharkiv, Ukraine
Provincial Hospitals in Gdynia Sp. z o.o. (LLC)
🇵🇱Gdynia, Poland
Regional Hospital of Bellinzona and Valli, Oncology Institute of Southern Switzerland
🇨🇭Bellinzona, Ticino, Switzerland
Kyiv City Clinical Hospital #9, City Hematology Center
🇺🇦Kyiv, Ukraine
Alabama Oncology
🇺🇸Birmingham, Alabama, United States
Abbott Northwestern Hospital, Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Novant Health Oncology
🇺🇸Winston-Salem, North Carolina, United States
University Hospital Brno
🇨🇿Brno, Czechia
University Hospital Hradec Kralove
🇨🇿Hradec Králové, Czechia
University Hospital Kralovske Vinohrady
🇨🇿Prague, Czechia
University of Debrecen Clinical Center
🇭🇺Debrecen, Hungary
United Hospitals Villa Sofia Cervello
🇮🇹Palermo, Italy
University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona
🇮🇹Ancona, Italy
National Institute of Oncology
🇭🇺Budapest, Hungary
General University Hospital in Prague
🇨🇿Prague, Czechia
Civil Hospital of Brescia
🇮🇹Brescia, Italy
Local Healthcare Company 8 Berica (Azienda ULSS8 Berica), Hospital San Bortolo of Vicenza
🇮🇹Vicenza, Italy
St. John of Dukla Oncology Center of Lublin Land
🇵🇱Lublin, Poland
National Research Center for Radiation Medicine
🇺🇦Kyiv, Ukraine
Podillia Regional Oncology Center
🇺🇦Vinnytsia, Ukraine
Carle Foundation Hospital, Cancer Center
🇺🇸Urbana, Illinois, United States