| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| CD20 positive B-Cell Non-Hodgkin Lymphoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Non-Hodgkin's lymphoma is a type of cancer that begins in your lymphatic system, which is part of the body's germ-fighting immune system. |
|
| 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 | 23.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10084346 |
| E.1.2 | Term | B-cell non-Hodgkin's lymphoma |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
● To evaluate the efficacy of glofitamab in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) chemoimmunotherapy, as assessed by the investigator based on achievement of a complete response (CR)
● To evaluate the safety and tolerability of glofitamab in combination with R-ICE chemoimmunotherapy
● To determine the pharmacokinetics of glofitamab alone and in combination with R-ICE chemoimmunotherapy |
|
| E.2.2 | Secondary objectives of the trial |
● To evaluate the anti-tumor activity of glofitamab in combination with R-ICE chemoimmunotherapy and glofitamab monotherapy
● To evaluate the safety and tolerability of glofitamab monotherapy
● To determine the pharmacokinetics of obinutuzumab and rituximab
● To evaluate the immune response to glofitamab |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
● Age 6 months to <18 years at the time of signing Informed Consent for Part 1 and Cohort B of the study, and age 6 months to <=30 years old at the time of signing Informed Consent for Part 2 of the study
● Histologically re-confirmed diagnosis, via tissue biopsy, or bone marrow aspirate, pleural effusion, or ascites, prior to study entry of aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) that expresses CD20 (reconfirmed by immunohistochemistry [IHC]), or flow cytometry if IHC is not possible including Burkitt lymphoma (BL), Burkitt leukemia (BAL) (mature B-cell leukemia fragment antigen-binding [FAB] L3), diffuse large B-cell lymphoma (DLBCL), and primary mediastinal large B-cell lymphoma (PMBCL), at the time of first relapsed or refractory (R/R) disease for Cohort A and second or greater R/R disease for Cohort B
● Refractory or relapsed disease (i.e., prior treatment was ineffective or intolerable) following first-line standard-of-care chemoimmunotherapy for Cohort A and following at least two prior systemic chemoimmunotherapy regimens and who have exhausted all available established therapies for Cohort B
● Measurable disease
● Adequate performance status, as assessed according to the Lansky or Karnofsky Performance Status scales
● Adequate bone marrow function
● Adequate liver and renal function
● Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection
● Negative test results for hepatitis C virus (HCV) and HIV
● For female participants of childbearing potential, or who will reach childbearing potential during the study: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for at least 18 months after obinutuzumab pretreatment, 2 months after the final dose of glofitamab, 12 months after the final dose of rituximab and/or ifosfamide, carboplatin, and etoposide (ICE), or 3 months after the final dose of tocilizumab
● For male participants who are expected to reach sexual maturity during the study, or have already reached sexual maturity by the screening visit: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for at least 3 months after pretreatment with obinutuzumab, 2 months after the final dose of glofitamab, 6 months after the final dose of rituximab and/or ICE, or 2 months after the last dose of tocilizumab (if applicable), whichever is longer, to avoid exposing the embryo
● Participants and/or caregivers who are willing and able to complete clinical outcome assessments throughout the study using either paper or interviewer methods |
|
| E.4 | Principal exclusion criteria |
● Isolated CNS disease of mature B-NHL without systemic involvement, and primary central nervous system (CNS) lymphoma
● Receipt of glofitamab prior to study enrollment
● Ongoing adverse events from prior anti-cancer therapy that were not resolved to Grade <=1
● Participants with active infections which are not resolved prior to Day 1 of Cycle 1
● Grade >=3 adverse events, with the exception of Grade 3 endocrinopathy managed with replacement therapy
● Patients with active infections which are not resolved prior to Day 1 of Cycle 1
● Prior solid organ transplantation
● Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
● Known or suspected chronic active Epstein-Barr viral infection (CAEBV)
● Active autoimmune disease requiring treatment
● History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
● History of confirmed progressive multifocal leukoencephalopathy
● Current or past history of uncontrolled non-malignant CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
● Evidence of significant and uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
● Major surgery or significant traumatic injury <28 days prior to the obinutuzumab pretreatment infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment
● Administration of a live, attenuated vaccine within 4 weeks before the start of study treatment (obinutuzumab pretreatment) or at any time during the study treatment period and within 12 months after end of study treatment
● Participants with any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
● Pregnancy or breastfeeding, or intention of becoming pregnant during the study
Exclusion criteria applicable to Cohort A only
● Receipt of any R-ICE chemoimmunotherapy prior to study enrollment into Cohort A
● Receipt of more than one prior line of standard-of-care B-NHL chemoimmunotherapy
● Prior allogeneic or autologous stem cell transplantation (SCT)
Exclusion criteria applicable to Cohort B only
● Prior treatment with systemic chemotherapy and immunotherapeutic agents
● Patients with uncontrolled CNS involvement
● Prior allogeneic or autologous SCT <=100 days post-transplant prior to enrollment
● Presence of Grade >=2 acute or extensive chronic graft -versus-host disease (GVHD) in participants who received prior allogeneic hematopoietic stem cell transplantation (HSCT)
● Prior treatment with systemic immunosuppressive agents for treatment of GVHD, within 4 weeks or five half-lives of the drug, whichever is shorter, before the first GpT infusion |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Achievement of a complete response (CR) after up to three cycles of treatment as determined by the investigator according to the International Pediatric NHL Response Criteria for pediatric participants and Lugano Classification for young adult participants (glofitamab plus R-ICE chemoimmunotherapy)
2. Incidence, nature, frequency, severity, and timing of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI CTCAE v5.0) (glofitamab plus R-ICE chemoimmunotherapy)
3. Change from baseline in physical findings, vital signs, clinical laboratory test results and electrocardiogram (ECG) (glofitamab plus R-ICE chemoimmunotherapy)
4. Pharmacokinetics (PK) parameters (as appropriate) and serum concentrations of glofitamab monotherapy at specified timepoints
5. PK parameters (as appropriate) and serum concentrations of glofitamab in combination with R-ICE chemoimmunotherapy at specified timepoints |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 9 weeks
2. Up to approximately 3 years
3. Baseline to 3 years (Until D21 of last cycle for ECG and laboratory parameters)
4. At Days 1, 8, 15 of Cycle 1; Day 1 of each cycle from Cycle 2, end of treatment (EOT), and first years follow-up
5. At Days 1, 8, 15 of Cycle 1; Day 1 of Cycle 2; Days 1, 5 of Cycle 3, at EOT, and first years follow up |
|
| E.5.2 | Secondary end point(s) |
1. For glofitamab plus R-ICE chemoimmunotherapy: Objective response rate (ORR), Duration of complete response (DOCR), Progression-free survival (PFS) after enrollment, Event-free survival (EFS), Overall survival (OS) and percentage of patients who proceed to HSCT after up to three cycles of treatment
2. For glofitamab monotherapy: ORR, Duration of response (DOR) and OS
3. Incidence, nature, frequency, severity, and timing of adverse events, with severity determined according to NCI CTCAE v5.0 (glofitamab monotherapy)
4. Change from baseline in physical findings, vital signs, clinical laboratory test results and ECG (glofitamab monotherapy)
5. Serum concentrations of obinutuzumab at specified timepoints
6. Serum concentrations of rituximab at specified timepoints
7. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs against glofitamab during the study |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3. Up to approximately 3 years
4. Baseline to 3 years (Until D21 of last cycle for ECG and laboratory parameters)
5. At Days 1, 8, 15 of Cycle 1
6. At Days 1, 5 of Cycle 3
7. At Days 1, 8 of Cycle 1; At Day 5 of Cycle 3, at EOT, and first years follow up
|
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability and anti-tumor activity |
|
| 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 |
| A phase I/II trial to evaluate glofitamab in combination with chemotherapy in pediatric patients |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| 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 | No |
| 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.8.2.4 | Number of treatment arms in the trial | 1 |
| 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 | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 10 |
| 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 |
| China |
| Denmark |
| France |
| Germany |
| Italy |
| Korea, Republic of |
| Spain |
| United States |
|
| 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
|
|
| 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 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
