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Completed

NCT Number: 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

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.

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Key information

Conditions

Diffuse Large B-cell Lymphoma B-cell Non-Hodgkin's Lymphoma Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

CHU UCL Namur asbl - Site Godinne, Yvoir, Namur, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • 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.

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.

Treatment and study plan

Debio 1562

Drug

Administered as IV Infusion.

Rituximab

Drug

Administered as IV Infusion.

Primary outcomes

  1. 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.

  2. 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).

  3. 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.

  4. 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.

  5. 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.

Secondary outcomes

  1. 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)

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

    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.

  9. 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

    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.

  10. 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

    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.

  11. 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

    OS was defined as the duration between the first dose date of Debio 1562 and the date of death due to any cause.

  12. 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)

    The potential immunogenicity against Debio 1562 was assessed in an ADA population.

Sponsors and collaborators

Lead sponsor

Debiopharm International SA

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2021
Study completion
2021
First posted
Oct 1, 2015
Registry last updated
Jun 12, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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