E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
diffuse large B-cell lymphoma (DLBCL) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012822 |
E.1.2 | Term | Diffuse large B-cell lymphoma refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10012819 |
E.1.2 | Term | Diffuse large B-cell lymphomas |
E.1.2 | System Organ Class | 100000004851 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- Evaluate and compare progression-free survival (PFS) between the 2 treatment arms in the intent-to-treat (ITT) population - Evaluate and compare PFS between the 2 treatment arms in the CD30-positive population |
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E.2.2 | Secondary objectives of the trial |
- Evaluate and compare the objective response rate (ORR) between the 2 treatment arms in the ITT population - Evaluate and compare overall survival (OS) between the 2 treatment arms in the ITT population - Evaluate and compare OS between the 2 treatment arms in the CD30-positive population - Evaluate and compare the complete response (CR) rate between the 2 treatment arms - Evaluate and compare duration of response between the 2 treatment arms - Evaluate the safety and tolerability of the 2 treatment arms |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Participants with relapsed or refractory diffuse and transformed large B-cell lymphoma (R/R DLBCL). DLBCL and cell of origin (GCB versus non-GCB) will be histologically determined by the most recent local pathology assessment for the purposes of study eligibility and stratification. - Participants must have R/R disease following 2 or more lines of prior systemic therapy. For subjects with transformed DLBCL (subtype k), at least the last systemic therapy used must have been for DLBCL. - Participants must be HSCT or CAR-T ineligible according to the investigator and must meet at least one of the following criteria: 1. One or more co-morbidities, including cardiac, pulmonary, renal or hepatic dysfunction that in the opinion of the Investigator make the subject medically unfit to received HSCT or CAR-T therapy 2. Active disease following induction and salvage chemotherapy 3.Inadequate stem cell mobilization (for HSCT) 4. Relapse following prior HSCT or CAR-T 5. Unable to receive CAR-T therapy due to financial, geographic, insurance or manufacturing issues - Participants must have tumor tissue submitted to the central pathology lab for the determination of CD30 expression. - An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2 - Participants must have fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET) and bidimensional measurable disease of >1.5 cm by computed tomography (CT), as assessed by the site radiologist within 28 days of Day 1.
Other protocol defined inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
- History of another malignancy within 2 years before the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. - History of progressive multifocal leukoencephalopathy (PML). - Active cerebral/meningeal disease related to the underlying malignancy. Subjects with a history of cerebral/meningeal disease related to the underlying malignancy are allowed if prior CNS disease has been effectively treated and without progression for at least 3 months. - Any uncontrolled Grade 3 or higher (per NCI CTCAE version 5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study drug. Routine antimicrobial prophylaxis is permitted - Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with immunotherapy that is not completed 3 weeks prior to first dose of study drug, unless underlying disease has progressed on treatment - Participants who are breastfeeding - Known hypersensitivity to any study drug or excipient contained in the drug formulation of the study drugs - Any contraindication to associated study treatments. - Known to be positive for hepatitis B by surface antigen expression. Subjects who are hepatitis B surface antigen (HBsAg) negative but hepatitis B core antibody (HBcAb) positive are eligible, but should start hepatitis B prophylaxis therapy prior to receiving the first dose of rituximab. Known to be positive for hepatitis C (HCV) infection (either confirmed positive by polymerase chain reaction [PCR] or on antiviral therapy for hepatitis C within the last 6 months). Participants who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of 12 weeks. - Participants with previous allogeneic HSCT if they meet either of the following criteria: 1.<100 days from HSCT 2.Active acute or chronic graft-versus-host disease (GVHD) or receiving immunosuppressive therapy as treatment for or prophylaxis against GVHD - Previous treatment with brentuximab vedotin or lenalidomide. Previous treatment with other vedotin-based ADCs is permitted if the last dose is at least 6 months prior to Day 1. - Current therapy with immunosuppressive medications (including steroids), other systemic anti-neoplastic, or investigational agents a) Prednisone (or equivalent) ≤10 mg/day may be used for non-lymphomatous purposes - Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, pulmonary embolism, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III-IV within 6 months prior to the first dose of study drugs - Congestive heart failure, Class III or IV, by the NYHA criteria - Grade 2 or higher peripheral sensory or motor neuropathy at baseline Other protocol defined exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- PFS per blinded independent central review (BICR) in the ITT population - PFS per BICR in the CD30-positive population. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Up to 1 year - Up to 1 year |
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E.5.2 | Secondary end point(s) |
- ORR per BICR - OS in the ITT population - OS in the CD30+ population - CR rate - Duration of objective response - Incidence, severity, and seriousness of adverse events (AEs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Up to 1 year - Up to 18 months - Up to 18 months - Up to 1 year - Up to 1 year - Up to 1 year |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 98 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Korea, Republic of |
Taiwan |
United States |
Switzerland |
Belgium |
Denmark |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Final OS analysis, which is expected to occur no later than 5 years after enrollment of the first subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 4 |