Diffuse Large B-Cell LymphomaPhase 2NCT02564744
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
A Phase 2 study testing Debio 1562 and Rituximab in people with Diffuse Large B-Cell Lymphoma and B-cell Non-Hodgkin's Lymphoma, run by Debiopharm International SA at 39 sites in 9 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma, B-cell Non-Hodgkin's Lymphoma
- What is being tested?
- Debio 1562 and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 39 sitesin 9 countries
- Study dates
- 5 Jun 2016to 25 Jun 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
39 sites in 9 countries.
39 sites in 9 countries
United States9 sites
Alabama Oncology
Birmingham, Alabama, 35211
Cleveland Clinic
Cleveland, Ohio, 44195
Baylor University Medical Center
Dallas, Texas, 75246
Abbott Northwestern Hospital, Virginia Piper Cancer Institute
Minneapolis, Minnesota, 55407
Abramson Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Swedish Medical Center
Seattle, Washington, 98104
Spartanburg Regional Healthcare System
Spartanburg, South Carolina, 29303
Carle Foundation Hospital, Cancer Center
Urbana, Illinois, 61801
Novant Health Oncology
Winston-Salem, North Carolina, 27103
Ukraine7 sites
Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center
Cherkasy, 18009
Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine
Kharkiv, 61024
Communal Non-profit enterprise "Regional Center of Oncology"
Kharkiv, 61070
National Institute of Cancer
Kyiv, 03022
National Research Center for Radiation Medicine
Kyiv, 03115
Kyiv City Clinical Hospital #9, City Hematology Center
Kyiv, 04112
Podillia Regional Oncology Center
Vinnytsia, 21029
Belgium4 sites
Jan Yperman Ziekenhuis
Ieper, West-Vlaanderen, 8900
University Hospitals Leuven, Campus Gasthuisberg
Leuven, 3000
St. Augustinus Hospital, Department of Hematology
Wilrijk, 2610
CHU UCL Namur asbl - Site Godinne
Yvoir, Namur, 5530
Czechia4 sites
University Hospital Brno
Brno, 625 00
University Hospital Hradec Kralove
Hradec Králové, 500 05
University Hospital Kralovske Vinohrady
Prague, 100 34
General University Hospital in Prague
Prague, 128 08
Italy4 sites
University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona
Ancona, 60126
Civil Hospital of Brescia
Brescia, 25123
United Hospitals Villa Sofia Cervello
Palermo, 90146
Local Healthcare Company 8 Berica (Azienda ULSS8 Berica), Hospital San Bortolo of Vicenza
Vicenza, 36100
Poland4 sites
University Clinical Center in Gdansk
Gdansk, 80-214
Provincial Hospitals in Gdynia Sp. z o.o. (LLC)
Gdynia, 81-519
Małopolskie Medical Centre
Krakow, 30-510
St. John of Dukla Oncology Center of Lublin Land
Lublin, 20-090
Bulgaria3 sites
University Multiprofile Hospital for Active Treatment "Sveti Georgi"
Plovdiv, 4002
Specialized Hospital for Active Treatment of Hematological Diseases,Clinic of Hematology
Sofia, 1756
Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa
Vratsa, 3000
Hungary3 sites
National Institute of Oncology
Budapest, H-1122
University of Debrecen Clinical Center
Debrecen, 4032
Medical Center of the University of Pecs
Pécs, H-7624
Switzerland1 site
Regional Hospital of Bellinzona and Valli, Oncology Institute of Southern Switzerland
Bellinzona, Canton Ticino, 6500
About this study
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
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.
- Being tested
- Debio 1562, Rituximab
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Debio 1562Drug
Administered as IV Infusion.
RituximabDrug
Administered as IV Infusion.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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). Receives: 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). Receives: 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). Receives: Drug: Debio 1562; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
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.
Measured: Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first
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.
Measured: Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first
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.
Measured: Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first
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.
Measured: Up to death or end of study (approximately 57 months) or one year from the last participant's first dose
Number of Participants With Anti-drug Antibodies (ADA) for Debio 1562
The potential immunogenicity against Debio 1562 was assessed in an ADA population.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2015 (estimated)
- Study start5 Jun 2016
- Primary completion13 Jan 2021
- Study completion25 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Debiopharm International SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02564744
- Sponsor's protocol ID
- Debio 1562-201
- Other IDs
- 2015-004061-87, 2015
- Status last verified
- May 2024
- First submitted
- 11 Sep 2015
- Last updated
- 12 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02564744
- Acronym / sponsor ID
- Debio 1562-201
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Debiopharm International SAIndustry (pharma, biotech, devices)
- Study start
- 5 Jun 2016 (actual)
- Primary completion
- 13 Jan 2021 (actual)
- Study completion
- 25 Jun 2021 (actual)
- First posted
- 1 Oct 2015 (estimated)
- Results
- Posted 17 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Part 1: Safety Run-in | Experimental | Drug: Debio 1562, Drug: RituximabParticipants 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 | Experimental | Drug: Debio 1562, Drug: RituximabParticipants 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 | Experimental | Drug: Debio 1562, Drug: RituximabParticipants 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 | Experimental | Drug: Debio 1562, Drug: RituximabParticipants 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 | Experimental | Drug: Debio 1562, Drug: RituximabParticipants 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Debio 1562Administered as IV Infusion. | Drug | Part 1: Cohort 1, Part 1: Cohort 2, Part 1: Safety Run-in, Part 2/3: Cohort A, Part 2/3: Cohort B |
| RituximabAdministered as IV Infusion. | Drug | Part 1: Cohort 1, Part 1: Cohort 2, Part 1: Safety Run-in, Part 2/3: Cohort A, Part 2/3: Cohort B |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: 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.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Test Results Reported as TEAEs
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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.
12 secondary outcomes
Maximum Plasma Drug Concentration (Cmax) of Debio 1562 and Rituximab
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Progression-free Survival (PFS)
Time frame: Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first
Time to Response (TTR)
Time frame: Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first
Duration of Response (DOR)
Time frame: Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first
Overall Survival (OS)
Time frame: Up to death or end of study (approximately 57 months) or one year from the last participant's first dose
Number of Participants With Anti-drug Antibodies (ADA) for Debio 1562
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
39 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Debio 1562 and Rituximab in people with Diffuse Large B-Cell Lymphoma and B-cell Non-Hodgkin's Lymphoma, run by Debiopharm International SA at 39 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States, Ukraine, Belgium, Czechia, Italy and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: Up to 30 days after end of treatment (EOT) (Up to 38 months)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2024.