E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
diffuse large B-cell lymphoma (DLBCL) |
lymphome diffus à grandes cellules B (LDGCB) |
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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 |
- Évaluer et comparer la survie sans progression (SSP) entre les 2 bras de traitement dans la population en intention de traiter (ITT)
- Évaluer et comparer la SSP entre les 2 bras de traitement dans la population CD30-positive
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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 |
- Évaluer et comparer le taux de réponse objective (TRO) entre les 2 bras de traitement dans la population ITT
- Évaluer et comparer la survie globale (SG) entre les 2 bras de traitement dans la population ITT
- Évaluer et comparer la SG entre les 2 bras de traitement dans la population CD30-positive
- Évaluer et comparer le taux de réponse complète (RC) entre les 2 bras de traitement
- Évaluer et comparer la durée de la réponse entre les 2 bras de traitement
- Évaluer la sécurité d’emploi et la tolérance dans les 2 bras de traitement
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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.
- 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, or insurance issues
- Participants will need to have a formalin-fixed paraffin-embedded tumor tissue (obtained ≤4 weeks before Day 1) submitted to the central pathology lab.
- 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 at least 1.5 cm by computed tomography (CT), as assessed by the site radiologist within 28 days of Day 1.
- Participants must be registered into the mandatory lenalidomide REMS® risk minimization programs and be willing to comply with its requirements. Per standard lenalidomide REMS® risk minimization programs requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the lenalidomide REMS® risk minimization programs.
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
- Known to be positive for hepatitis B by surface antigen expression. Known to be positive for hepatitis C infection (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
- 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, 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. |
- SSP selon un examen central indépendant en aveugle (ECIA) dans la population ITT
- SSP selon l’ECIA dans la population CD30-positive.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Up to 1 year
- Up to 1 year |
-Jusqu'à 1 an
-Jusqu'à 1 an |
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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) |
- TRO selon l’ECIA
- SG dans la population ITT
- SG dans la population CD30+
- Taux de RC
- Durée de la réponse objective
- Incidence, sévérité, et gravité des événements indésirables (EI) |
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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 |
- Jusqu'à 1 an
- Jusqu'à 18 mois
- Jusqu'à 18 mois
- Jusqu'à 1 an
- Jusqu'à 1 an
- Jusqu'à 1 an |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 26 |
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 |
Belgium |
Canada |
Denmark |
France |
Germany |
Italy |
Korea, Republic of |
Netherlands |
Poland |
Spain |
Switzerland |
Taiwan |
United Kingdom |
United States |
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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
|
Final OS analysis, which is expected to occur no later than 5 years after enrollment of the first subject. |
Analyse finale de la SG, qui est attendue pas plus tard que 5 ans après l'inclusion du premier patient |
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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 | 10 |
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 |