E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed/refractory Burkitt's or Burkitt-like lymphoma/leukemia, Diffuse large B-cell lymphoma , or other aggressive mature (CD20+) B-cell lymphomas
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E.1.1.1 | Medical condition in easily understood language |
Lymphoma of B-cell origin
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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 | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10006596 |
E.1.2 | Term | Burkitt's lymphomas |
E.1.2 | System Organ Class | 100000004851 |
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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 | 10003903 |
E.1.2 | Term | 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 | 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.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives of the study are to evaluate the safety and Pharmacokinetic profile of epcoritamab monotherapy in pediatric patients (and young adults) with relapsed/refractory Burkitt's or Burkitt-like lymphoma/leukemia, DLBCL, or other aggressive mature (CD20+) B-cell lymphomas who have failed to reach remission with re-induction therapy or who are unable to receive further consolidation with cell therapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to evaluate the preliminary efficacy and immunogenicity of epcoritamab monotherapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects ≥ 1 and < 18 years old at time of primary diagnosis with Burkitt's or Burkitt-like lymphoma/leukemia, DLBCL, or other aggressive mature (CD20+) B-cell lymphomas. Patients up to 25 years of age with Burkitt's or Burkitt-like lymphoma/leukemia are also eligible.
2. Disease pathologically confirmed (tumor tissue) by local testing.
3. Patients with relapsed or primary refractory disease (as above) meeting any of the following criteria: •Progressive disease at any time during second-line chemoimmunotherapy •Best response of stable disease (SD) after a minimum of 2 cycles of second-line chemoimmunotherapy •Best response of partial response (PR) after a minimum of 3 cycles of second-line chemoimmunotherapy •Complete Response after a minimum of 3 cycles of second-line chemoimmunotherapy therapy but unfit or ineligible for consolidation with cell therapy •Not in Complete response and unable to initiate or tolerate (i.e., must discontinue) second-line chemoimmunotherapy •Have received cell therapy (allogeneic or autologous transplant or CAR-T therapy) as consolidation but have not obtained or maintained a complete response
4. Recovery from toxic effects of prior chemoimmunotherapy
5. Performance status by Lansky (< 16 years old at evaluation) or Karnofsky (≥ 16 years old at evaluation) score ≥ 50 or ECOG score ≤ 2
6. Adequate bone marrow, hepatic, and renal function.
7. For those patients who have not reached the age of consent, parent or legal guardian with the willingness and ability to provide written informed consent and subject willing and able to give assent, as appropriate for age and country.
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E.4 | Principal exclusion criteria |
1. Known CNS involvement by lymphoma at screening as confirmed by screening MRI/CT/PET brain scans (patients with evidence of CNS disease only in the CSF will be eligible).
2. Currently receiving anti-cancer therapy, including chemotherapy (excluding intrathecal therapy), radiotherapy, small molecules, monoclonal antibodies, cell therapy, or other investigational agents.
3. Other malignancy requiring therapy. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are safety and tolerability, including adverse events of special interest (AESIs) of Cytokine Release Syndrome (CRS), Immune Cell-Associated Neurotoxicity Syndrome (ICANS), and Clinical Tumor Lysis Syndrome (CTLS), and PK parameters of epcoritamab monotherapy.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety and tolerability are evaluated throughout the study.
Pharmacokinetic parameters are evaluated the following timepoint: • Cycle 1: Day 10, Day 15-17, Day 19, Day 22 •Cycle 2: Day 1, Day 8-10, Day 12, Day 15 •Cycle 3-10: Day 1
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E.5.2 | Secondary end point(s) |
•Complete response rate (CR) per the International Pediatric Non- Hodgkin Lymphoma Response Criteria •Event free survival (EFS) •Overall survival (OS) •Rate of initiation of stem cell transplantation or chimeric antigen receptor T-cell (CAR-T) therapy •Overall Response (OR) •Duration of response (DOR) •Duration of complete response (DOCR) •Immunogenicity (antidrug antibody [ADA] and neutralizing anti-drug antibodies [nAb]) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Disease evaluation (CT/MRI/PET) will be performed for all patients prior to administration of epcoritamab on Day 1 and at the following time points relative to Day 1: W6, W12, W24, W36, W48, 18 months, and 24 months, as well as prior to initiation of subsequent therapy, and as clinically indicated. Patients who do not attain a CR during therapy with epcoritamab will have additional disease assessments at W18, W30, W42, and every 3 months thereafter. Patients will be followed for a minimum of 3 years after enrollment. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 |
Czechia |
France |
Germany |
Israel |
Italy |
Korea, Republic of |
Netherlands |
Russian Federation |
Spain |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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The end-of-study is defined as the date of the last subject's last visit or date of the last follow-up contact, whichever is later. |
La fin de l'étude est définie comme la date de la dernière visite du dernier patient ou la date du dernier contact de suivi, la date la plus tardive étant retenue.
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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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |