Ifosfamide for Mature B-cell non-Hodgkin lymphoma | CD20-positive B-cell non-Hodgkin lymphoma

Inclusion criteria

• {"criterion_text":"- Age 6 months to <18 years at the time of signing Informed Consent for Cohort A Part 1 and Cohort B of the study, and age 6 months to < 30 years old at the time of signing Informed Consent for Cohort A Part 2 of the study Cohort A Part 2–18 up to < 30 years old, is restricted to young adults with first relapsed or refractory (R/R) aggressive mature B-NHL for whom no alternative standard-of-care treatment is available\n- 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\n- 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, defined as – At least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension or – Percentage of bone marrow involvement with lymphoma cells defined by cytomorphological analysis of bone marrow aspirates\n- Adequate performance status, as assessed according to the Lansky or Karnofsky Performance Status scales\n- Adequate bone marrow, liver and renal function\n- Negative test results for hepatitis B and hepatitis C viruses (HBV and HCV), human immunodeficiency virus (HIV) and severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2)."}

Exclusion criteria

• {"criterion_text":"- Exclusion criteria applicable to both Cohorts A and B - Isolated CNS disease of mature B-NHL without systemic involvement, and primary central nervous system (CNS) lymphoma\n- Exclusion criteria applicable to Cohorts A only - Receipt of glofitamab prior to study enrollment\n- Exclusion criteria applicable to Cohort A only - Receipt of any R-ICE chemoimmunotherapy prior to study enrollment into Cohort A\n- Exclusion criteria applicable to Cohort A only - Receipt of more than one prior line of standard-of-care B-NHL chemoimmunotherapy\n- Exclusion criteria applicable to Cohort B only - Prior treatment with standard radiotherapy (within 2 weeks before Day 1 of Cycle 1), systemic chemotherapy and immunotherapeutic anticancer agents (within 4 weeks or five half-lives of the drug, before Day 1 of Cycle 1)\n- Exclusion criteria applicable to Cohort B only - Patients with uncontrolled CNS involvement"}

Primary endpoints

• {"endpoint_text":"- Cohort A - Glofitamab Combination Therapy (glofitamab plus R-ICE chemoimmunotherapy) 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","definition_or_measurement_approach":"CR determined by investigator per International Pediatric NHL Response Criteria for pediatric participants and per Lugano Classification for young adult participants after up to three cycles of treatment."}
• {"endpoint_text":"- Cohort A - Glofitamab Combination Therapy (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)","definition_or_measurement_approach":"Adverse events recorded and graded according to NCI CTCAE v5.0; incidence, nature, frequency, severity and timing captured for glofitamab plus R-ICE."}
• {"endpoint_text":"- Cohort A - Glofitamab Combination Therapy (glofitamab plus R-ICE chemoimmunotherapy) 3. Change from baseline in physical findings, vital signs, clinical laboratory test results and electrocardiogram (ECG) parameters","definition_or_measurement_approach":"Clinically measured changes from baseline in physical exam findings, vital signs, lab tests and ECG parameters at prespecified timepoints."}
• {"endpoint_text":"- 4. Pharmacokinetics (PK) parameters (as appropriate) and serum concentrations of glofitamab monotherapy at specified timepoints","definition_or_measurement_approach":"PK parameters and serum concentrations measured at specified timepoints for glofitamab monotherapy (assays and sampling schedule per protocol)."}
• {"endpoint_text":"- 5. PK parameters (as appropriate) and serum concentrations of glofitamab in combination with R-ICE chemoimmunotherapy at specified timepoints","definition_or_measurement_approach":"PK parameters and serum concentrations measured at specified timepoints for glofitamab when given with R-ICE (assays and sampling schedule per protocol)."}

Secondary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Tumor response metrics (ORR, DOCR), time-to-event endpoints (PFS, EFS, OS) and proportion proceeding to HSCT; assessed per protocol-defined response criteria and follow-up schedule."}
• {"endpoint_text":"- 2. For glofitamab monotherapy: ORR, Duration of response (DOR) and OS","definition_or_measurement_approach":"ORR, DOR and OS assessed per protocol-defined response criteria and follow-up."}
• {"endpoint_text":"- Glofitamab monotherapy 3. Incidence, nature, frequency, severity, and timing of adverse events, with severity determined according to NCI CTCAE v5.0","definition_or_measurement_approach":"Adverse events recorded and graded by NCI CTCAE v5.0 for glofitamab monotherapy."}
• {"endpoint_text":"- Glofitamab monotherapy 4. Change from baseline in physical findings, vital signs, clinical laboratory test results and ECG parameters","definition_or_measurement_approach":"Clinical and laboratory parameter changes from baseline measured at specified timepoints."}
• {"endpoint_text":"- 5. Serum concentrations of obinutuzumab at specified timepoints","definition_or_measurement_approach":"Serum concentration sampling and assays for obinutuzumab at protocol-specified timepoints."}
• {"endpoint_text":"- 6. Serum concentrations of rituximab at specified timepoints","definition_or_measurement_approach":"Serum concentration sampling and assays for rituximab at protocol-specified timepoints."}
• {"endpoint_text":"- 7. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs against glofitamab during the study","definition_or_measurement_approach":"Baseline prevalence and on-study incidence of anti-drug antibodies assessed by immunogenicity assays at specified timepoints."}

Methods

• Recruitment arrangements documents available (K_Recruitment arrangements) indicating formal recruitment materials were prepared for publication
• Physician-to-physician referral letter (document title: K2_Recrutiment_Physician-to-physician referral letter)
• Patient card materials (document titles include K2_Patient card, L2_Patient card)
• Site-based recruitment via participating hospitals/clinical centers (multiple site-specific recruitment arrangement documents listed)

Denmark

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

20-01-2026

Processing Time Days

672

Number Of Sites

1

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

680

Number Of Sites

2

Number Of Participants

5

Czechia

Earliest CTIS Part Ii Submission Date

27-06-2025

Latest Decision Or Authorization Date

23-01-2026

Processing Time Days

210

Number Of Sites

1

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

21-01-2026

Processing Time Days

673

Number Of Sites

2

Number Of Participants

5

France

Earliest CTIS Part Ii Submission Date

02-04-2024

Latest Decision Or Authorization Date

20-01-2026

Processing Time Days

688

Number Of Sites

2

Number Of Participants

5

Poland

Earliest CTIS Part Ii Submission Date

07-07-2025

Latest Decision Or Authorization Date

30-01-2026

Processing Time Days

207

Number Of Sites

1

Number Of Participants

4

Germany

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

22-01-2026

Processing Time Days

674

Number Of Sites

1

Number Of Participants

5

Hungary

Earliest CTIS Part Ii Submission Date

03-06-2025

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

239

Number Of Sites

1

Number Of Participants

4

Primary sponsor

Full Name

F. Hoffmann-La Roche AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Pharmaceutical Product Development LLC

Name

Iqvia Rds Inc.

Responsibilities

Monitoring

Name

Labcorp Central Laboratory Services LP

Name

Frontage Laboratories Inc.

Name

Almac Clinical Technologies LLC

Third parties

• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"QPS Netherlands B.V.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Other Third Party Duty","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"BioClinica GmbH","duties_or_roles":"Other Third Party Duty","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Rds Inc.","duties_or_roles":"Monitoring","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Myriad RBM Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"China","full_name":"Q Squared Solutions (Beijing) Co. Ltd.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}