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OpenTrials
Completed

NCT Number: NCT05364424

A Study Evaluating the Efficacy, Safety, and Pharmacokinetics of Glofitamab in Combination With Rituximab Plus Ifosfamide, Carboplatin Etoposide Phosphate in Participants With Relapsed/Refractory Transplant or CAR-T Therapy Eligible Diffuse B-Cell Lymphoma

The purpose of this study is to evaluate the preliminary efficacy, safety, and pharmacokinetics of glofitamab (glofit) in combination with rituximab plus ifosfamide, carboplatin, and etoposide (R-ICE) in participants with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), who have failed one prior line of therapy incorporating an anti-cluster of differentiation (CD) 20 antibody (i.e., rituximab) and an anthracycline, and who are transplant or chimeric antigen receptor T-cell (CAR-T) therapy eligible, defined as being medically eligible for intensive platinum-based salvage therapy followed by autologous stem cell transplantation (ASCT) or for CAR-T therapy.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Chao Family Comprehensive Cancer Center UCI, Orange, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Life expectancy ≥ 12 weeks
  • Histologically confirmed B-cell lymphoma
  • One line of prior systemic therapy including an anti-CD20 monoclonal antibody (i.e. rituximab) and an anthracycline
  • Relapsed or refractory disease after first-line chemoimmunotherapy
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Participant must be a candidate for high-dose chemotherapy followed by ASCT or CAR-T therapy

Exclusion criteria

  • Treatment with more than one prior line of therapy for DLBCL
  • Primary mediastinal B-cell lymphoma
  • Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
  • Peripheral neuropathy assessed to be Grade > 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 at enrollment
  • Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment
  • Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment
  • Primary or secondary CNS lymphoma at the time of enrollment or history of CNS lymphoma
  • Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
  • Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
  • Known history of progressive multifocal leukoencephalopathy
  • Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better (with the exception of alopecia and anorexia, or as otherwise permitted by inclusion criteria)
  • Prior solid organ transplantation
  • Prior allogeneic stem cell transplant
  • Prior ASCT for lymphoma
  • Prior autologous stem cell transplant for any indication other than lymphoma, within 5 years from the start of study treatment
  • Active autoimmune disease requiring treatment
  • Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), within 4 weeks prior to first dose of study treatment
  • Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Participants who received corticosteroid treatment with ≤ 30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to Cycle 1 Day 1. Participants may have received a brief (≤ 7 days) course of systemic steroids (≤ 100 mg prednisone equivalent per day) prior to initiation of study therapy for control of lymphoma-related symptoms
  • Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
  • Clinically significant history of cirrhotic liver disease

Treatment and study plan

Glofitamab

Drug

Participants will receive intravenous (IV) glofitamab for up to 3 cycles.

Obinutuzumab

Drug

Participants will receive IV obinutuzumab on Cycle 1 Day 1.

Tocilizumab

Drug

Participants will receive IV tocilizumab as necessary to manage cytokine release syndrome (CRS) events.

Rituximab

Drug

Participants will receive up to 2 doses of IV rituximab.

ifosfamide

Drug

Participants will receive IV ifosfamide for up to 3 cycles.

carboplatin

Drug

Participants will receive IV carboplatin for up to 3 cycles.

etoposide

Drug

Participants will receive IV etoposide for up to 3 cycles.

Primary outcomes

  1. Objective response rate (ORR), defined as the proportion of participants that achieves a CR or PR within three cycles of glofit-R-ICE, as determined by the investigator according to Lugano criteria

    Time frame: Up to 2.5 years

Secondary outcomes

  1. Event-free survival (EFS) after enrollment

    Time frame: From enrollment to the first occurrence of disease progression, initiation of new anti-lymphoma therapy (not including planned ASCT or CAR-T therapy), or death from any cause (whichever occurs first) (up to 2.5 years)

  2. Progression-free survival (PFS) after enrollment

    Time frame: From enrollment to the first occurrence of disease progression or death from any cause (whichever occurs first) as determined by the investigator according to Lugano criteria (up to 2.5 years)

  3. Mobilization-adjusted response rate (MARR)

    Time frame: Up to 2.5 years

    The proportion of participants treated with intent to proceed to ASCT that achieves a CR or PR within three cycles of glofit-R-ICE, as determined by the investigator according to Lugano criteria, and additionally achieves mobilization of a minimum of 2,000,000 CD34+ hematopoietic stem cells/kg for ASCT

  4. Overall survival (OS) after enrollment

    Time frame: From enrollment to death from any cause (up to 2.5 years)

  5. CR rate after enrollment, defined as the proportion of participants that achieves a CR within three cycles of glofit-R-ICE, as determined by the investigator according to Lugano criteria

    Time frame: Up to 2.5 years

  6. Duration of Response (DOR)

    Time frame: From the first occurrence of a documented objective response (CR or PR) to disease progression or death from any cause (whichever occurs first) as determined by the investigator according to Lugano criteria (up to 2.5 years)

  7. Duration of complete response (DOCR)

    Time frame: From the first occurrence of a documented complete response to disease progression or death from any cause (whichever occurs first) as determined by the investigator according to Lugano criteria (up to 2.5 years)

  8. Percentage of participants with adverse events (AEs)

    Time frame: Up to 2.5 years

  9. Percentage of participants with cytokine release syndrome (CRS)

    Time frame: Up to 2.5 years

  10. Maximum serum concentration (Cmax) of glofitamab

    Time frame: Up to 2.5 years

  11. Minimum serum concentration (Cmin) of glofitamab

    Time frame: Up to 2.5 years

  12. Percentage of participants with anti-drug antibodies (ADAs)

    Time frame: From baseline up to 2.5 years

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Phase IB, Open-Label, Multicenter, Single Arm Study Evaluating the Preliminary Efficacy, Safety, and Pharmacokinetics of Glofitamab in Combination With Rituximab Plus Ifosfamide, Carboplatin Etoposide Phosphate in Patients With Relapsed/Refractory Transplant or CAR-T Therapy Eligible Diffuse B-Cell Lymphoma

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
May 6, 2022
Registry last updated
Dec 1, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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