Active, currently enrolling
A Phase I/II, Open-Label, Single-Arm, Two-Part Trial to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of Glofitamab in Monotherapy and in Combination With Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma
NCT No.: NCT05533775
Study Type: INTERVENTIONAL
Phase:
Phase I, Phase II
Region: California - Northern
Acronym: iMATRIX GLO
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 Monotherapy and in Combination With Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma
Purpose
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).
Detailed Description
Eligibility 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
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; Histologically re-confirmed diagnosis, via tissue biopsy, or bone marrow aspirate, pleural effusion, or ascites, prior to study entry of aggressive mature B-NHL that expresses CD20 (reconfirmed by IHC or flow cytometry if IHC is not possible), 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
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; 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
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; 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
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; 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%
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; Adequate bone marrow, liver, and renal function
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; Negative test results for acute or chronic hepatitis B virus (HBV), hepatitis C virus (HCV)
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; Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count =200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months
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; Negative SARS-CoV-2 antigen or PCR test within 7 days prior to enrollment
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; Participants and/or caregivers who are willing and able to complete clinical outcome assessments throughout the study using either paper or interviewer methods
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Exclusion Criteria
Isolated CNS disease of mature B-NHL without systemic involvement, and primary CNS lymphoma
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; Receipt of glofitamab prior to study enrollment
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; Ongoing adverse events from prior anti-cancer therapy that were not resolved to Grade = 1 (exceptions: alopecia, Grade 2 peripheral neuropathy)
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; Grade = 3 adverse events, with the exception of Grade 3 endocrinopathy managed with replacement therapy
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; Participants with active infections which are not resolved prior to Day 1 of Cycle 1
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; Prior solid organ transplantation
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; Known or suspected history of hemophagocytic lymphohistiocytosis (HLH), or chronic active Epstein-Barr viral infection (CAEBV)
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; Active autoimmune disease requiring treatment
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; 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)
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; History of confirmed progressive multifocal leukoencephalopathy
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; Current or past history of uncontrolled non-malignant CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
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; Evidence of significant and uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
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; 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
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; 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
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; 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
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Keywords and/or Specific Medical Conditions
Sponsors
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