Clinical trial NCT02564744: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
B-cell Non-Hodgkin's Lymphoma
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2015-10-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 30 days after end of treatment (EOT) (Up to 38 months)
measure: Number of Participants With Clinically Significant Changes in Clinical Laboratory Test Results Reported as TEAEs
timeFrame: Up to 30 days after EOT (Up to 38 months)
measure: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Reported as TEAEs
timeFrame: Up to 30 days after EOT (Up to 38 months)
measure: Number of Participants With Clinically Significant Changes in Vital Sign Measurements Reported as TEAEs
timeFrame: Up to 30 days after EOT (Up to 38 months)
measure: Objective Response Rate (ORR)
timeFrame: Up to Progressive Disease (PD) or death (up to approximately 55 months) or initiation of new anti-cancer therapy whichever occurs first
Secondary outcomes:
measure: Maximum Plasma Drug Concentration (Cmax) of Debio 1562 and Rituximab
timeFrame: 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)
measure: Area Under the Time-concentration Curve From Time 0 to t (AUC0-t) of Debio 1562 and Rituximab
timeFrame: 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
measure: Area Under the Time-concentration Curve From Time 0 to Infinity (AUC0-inf) of Debio 1562 and Rituximab
timeFrame: 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
measure: Terminal Half-life (t1/2) of Debio 1562 and Rituximab
timeFrame: 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
measure: Clearance (CL) of Debio 1562 and Rituximab
timeFrame: 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
measure: Volume of Distribution at Steady State (Vss) of Debio 1562 and Rituximab
timeFrame: 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
measure: Time to Maximum Plasma Concentration (Tmax) of Debio 1562 and Rituximab
timeFrame: 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
measure: Progression-free Survival (PFS)
timeFrame: Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first
measure: Time to Response (TTR)
timeFrame: Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first
measure: Duration of Response (DOR)
timeFrame: Up to PD or death or end of study (approximately 57 months) or initiation of new anti-cancer therapy whichever occurs first
measure: Overall Survival (OS)
timeFrame: Up to death or end of study (approximately 57 months) or one year from the last participant's first dose
measure: Number of Participants With Anti-drug Antibodies (ADA) for Debio 1562
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology
state: Alabama
city: Urbana
country: United States
facility: Carle Foundation Hospital, Cancer Center
state: Illinois
city: Minneapolis
country: United States
facility: Abbott Northwestern Hospital, Virginia Piper Cancer Institute
state: Minnesota
city: Winston-Salem
country: United States
facility: Novant Health Oncology
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Abramson Cancer Center of The University of Pennsylvania
state: Pennsylvania
city: Spartanburg
country: United States
facility: Spartanburg Regional Healthcare System
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Yvoir
country: Belgium
facility: CHU UCL Namur asbl - Site Godinne
state: Namur
city: Ieper
country: Belgium
facility: Jan Yperman Ziekenhuis
state: West-Vlaanderen
city: Leuven
country: Belgium
facility: University Hospitals Leuven, Campus Gasthuisberg
city: Wilrijk
country: Belgium
facility: St. Augustinus Hospital, Department of Hematology
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sveti Georgi"
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Hematological Diseases,Clinic of Hematology
city: Vratsa
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Hristo Botev, Vratsa
city: Brno
country: Czechia
facility: University Hospital Brno
city: Hradec Králové
country: Czechia
facility: University Hospital Hradec Kralove
city: Prague
country: Czechia
facility: University Hospital Kralovske Vinohrady
city: Prague
country: Czechia
facility: General University Hospital in Prague
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Debrecen
country: Hungary
facility: University of Debrecen Clinical Center
city: Pécs
country: Hungary
facility: Medical Center of the University of Pecs
city: Ancona
country: Italy
facility: University Hospital - Ospedali Riuniti Umberto I - GM Lancisi - G Salesi of Ancona
city: Brescia
country: Italy
facility: Civil Hospital of Brescia
city: Palermo
country: Italy
facility: United Hospitals Villa Sofia Cervello
city: Vicenza
country: Italy
facility: Local Healthcare Company 8 Berica (Azienda ULSS8 Berica), Hospital San Bortolo of Vicenza
city: Gdańsk
country: Poland
facility: University Clinical Center in Gdansk
city: Gdynia
country: Poland
facility: Provincial Hospitals in Gdynia Sp. z o.o. (LLC)
city: Kraków
country: Poland
facility: Małopolskie Medical Centre
city: Lublin
country: Poland
facility: St. John of Dukla Oncology Center of Lublin Land
city: Bellinzona
country: Switzerland
facility: Regional Hospital of Bellinzona and Valli, Oncology Institute of Southern Switzerland
state: Ticino
city: Cherkasy
country: Ukraine
facility: Cherkasy Regional Oncology Center, Regional Treatment and Diagnostic Hematology Center
city: Kharkiv
country: Ukraine
facility: Grigoriev Institute for Medical Radiology and Oncology of the National Academy of Medical Sciences of Ukraine
city: Kharkiv
country: Ukraine
facility: Communal Non-profit enterprise "Regional Center of Oncology"
city: Kyiv
country: Ukraine
facility: National Institute of Cancer
city: Kyiv
country: Ukraine
facility: National Research Center for Radiation Medicine
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #9, City Hematology Center
city: Vinnytsia
country: Ukraine
facility: Podillia Regional Oncology Center
Study officials:
References: