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A Study to Evaluate Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma (iMATRIX GLO)

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ClinicalTrials.gov Identifier: NCT05533775
Recruitment Status : Recruiting
First Posted : September 9, 2022
Last Update Posted : December 1, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
The purpose of this study is to evaluate the safety and efficacy of glofitamab, as monotherapy and in combination with a standard chemoimmunotherapy regimen: rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in pediatric and young adult participants with relapsed and refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL).

Condition or disease Intervention/treatment Phase
Mature B-Cell Non-Hodgkin Lymphoma Drug: Obinutuzumab Drug: Glofitamab Drug: Rituximab Drug: Ifosfamide Drug: Carboplatin Drug: Etoposide Drug: Tocilizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Allocation: N/A
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-Label, Single-Arm, Two-Part Trial to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of Glofitamab in Combination With Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma
Estimated Study Start Date : December 15, 2022
Estimated Primary Completion Date : October 15, 2027
Estimated Study Completion Date : October 15, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Arm A
Participants will receive glofitamab + R-ICE chemoimmunotherapy for up to 3 cycles (cycle length = 21 days).
Drug: Obinutuzumab
Participants will receive intravenous (IV) obinutuzumab pretreatment on Days 1 and 2 of Cycle 1 (Cycle length = 21 days)

Drug: Glofitamab

Arm A: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of Cycles 2 and 3

Arm B: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of each cycle thereafter

(Cycle length = 21 days)


Drug: Rituximab
Participants will receive IV rituximab on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)

Drug: Ifosfamide
Participants will receive IV ifosfamide on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)

Drug: Carboplatin
Participants will receive IV carboplatin on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)

Drug: Etoposide
Participants will receive IV etoposide on Days 3, 4, and 5 of cycle 1 and on Days 5, 6, 7, and 8 of Cycles 2 and 3 (Cycle length = 21 days)

Drug: Tocilizumab
Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events

Experimental: Arm B
Participants will receive glofitamab monotherapy for up to 12 cycles (cycle length = 21 days).
Drug: Obinutuzumab
Participants will receive intravenous (IV) obinutuzumab pretreatment on Days 1 and 2 of Cycle 1 (Cycle length = 21 days)

Drug: Glofitamab

Arm A: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of Cycles 2 and 3

Arm B: Participants will receive IV glofitamab on Days 8 and 15 of Cycle 1, then on Day 1 of each cycle thereafter

(Cycle length = 21 days)


Drug: Tocilizumab
Participants will receive IV tocilizumab as needed to manage cytokine release syndrome (CRS) events




Primary Outcome Measures :
  1. Achievement of a complete response (CR) as determined by the investigator according to the International Pediatric NHL Response Criteria for pediatric participants and Lugano Classification for young adult participants (Arm A) [ Time Frame: Up to 3 treatment cycles (cycle length = 21 days) ]
  2. Percentage of participants with adverse events (AEs) (Arm A) [ Time Frame: Approximately 14 months ]
  3. Serum concentration of glofitamab in combination with R-ICE chemoimmunotherapy (Arm A) [ Time Frame: Up to 3 treatment cycles (cycle length = 21 days) ]
  4. Serum concentration of glofitamab monotherapy (Arm B) [ Time Frame: Up to 12 treatment cycles (Arm B) (cycle length = 21 days) ]

Secondary Outcome Measures :
  1. Objective response rate (ORR) (Arms A and B) [ Time Frame: Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days) ]
  2. Duration of complete response (DOCR) (Arm A) [ Time Frame: From the first occurrence of a documented complete response (CR) to documented disease progression or death from any cause (whichever occurs first) (approximately 14 months) ]
  3. Progression-free survival (PFS) (Arm A) [ Time Frame: From enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) (approximately 14 months) ]
  4. Event-free survival (EFS) (Arm A) [ Time Frame: From enrollment to the first occurrence of disease progression, death from any cause, or start of new anti-lymphoma therapy (not including planned hematopoietic stem cell transplantation (HSCT)) (approximately 14 months) ]
  5. Overall survival (OS) (Arms A and B) [ Time Frame: From the first study treatment to the date of death from any cause (Arm A = approximately 14 months, Arm B = approximately 20 months) ]
  6. Percentage of participants who proceed to HSCT after up to three cycles of treatment (Arm A) [ Time Frame: Up to 3 treatment cycles (cycle length = 21 days) ]
  7. Duration of response (DOR) (Arm B) [ Time Frame: From the first occurrence of a documented CR or partial response (PR) until documented disease progression or death from any cause, whichever occurs first (approximately 20 months) ]
  8. Percentage of participants with AEs (arm B) [ Time Frame: Approximately 20 months ]
  9. Serum concentration of obinutuzumab (Arms A and B) [ Time Frame: Up to 3 (Arm A) or 12 (Arm B) treatment cycles (cycle length = 21 days) ]
  10. Serum concentration of rituximab (Arm A) [ Time Frame: Up to 3 treatment cycles (cycle length = 21 days) ]
  11. Percentage of participants with anti-drug antibodies (ADAs) (Arms A and B) [ Time Frame: Up to 3 treatment cycles (cycle length = 21 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Months to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 prior to study entry of aggressive mature B-NHL that expresses CD20 (reconfirmed by IHC), including BL, BAL (mature B-cell leukemia FAB L3), DLBCL, and PMBCL, at the time of first R/R disease for Cohort A and second or greater R/R disease for Cohort B
  • Refractory or relapsed disease following first-line standard-of-care chemoimmunotherapy for Cohort A and following at least two prior systemic chemoimmunotherapy regimens 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
  • Adequate performance status, as assessed according to the Lansky or Karnofsky Performance Status scales: Participants < 16 years old: Lansky Performance Status ≥ 50%; Participants ≥ 16 years old: Karnofsky Performance Status ≥ 50%
  • Adequate bone marrow, liver, and renal function
  • Negative test results for acute or chronic hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
  • Participants and/or caregivers who are willing and able to complete clinical outcome assessments throughout the study using either paper or interviewer methods

Exclusion Criteria:

  • Isolated CNS disease of mature B-NHL without systemic involvement, and primary CNS lymphoma
  • Receipt of glofitamab prior to study enrollment
  • Ongoing adverse events from prior anti-cancer therapy that were not resolved to Grade ≤ 1 (exceptions: alopecia, Grade 2 peripheral neuropathy)
  • Grade ≥ 3 adverse events, with the exception of Grade 3 endocrinopathy managed with replacement therapy
  • Prior solid organ transplantation
  • Known or suspected history of hemophagocytic lymphohistiocytosis (HLH), or 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, except if the participant was able to safely receive it after initial administration (consider consultation with Medical Monitor)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05533775


Contacts
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Contact: Reference Study ID Number: CO43810 https://forpatients.roche.com 888-662-6728 global-roche-genentech-trials@gene.com

Locations
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Denmark
Rigshospitalet; Ny Medicin til Børn med Kræft Recruiting
København Ø, Denmark, 2100
Spain
Hospital Infantil Universitario Niño Jesus; Servicio de Onco-hematologia Recruiting
Madrid, Spain, 28009
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-LaRoche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT05533775    
Other Study ID Numbers: CO43810
First Posted: September 9, 2022    Key Record Dates
Last Update Posted: December 1, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hoffmann-La Roche:
Relapsed
Refractory
Pediatrics
B-NHL
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Obinutuzumab
Carboplatin
Etoposide
Ifosfamide
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents