A Multicentre, Parallel Arm, Open-label Trial of Frontline R-CHOP/Pola-RCHP and Glofitamab in Younger, Higher Risk Patients With Diffuse Large B Cell Lymphoma (DLBCL)

NCT04914741 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 20/047
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 15

Brief Summary

This is an open label, multi-centre, phase Ib/II, parallel arm study evaluating the safety and tolerability of glofitamab in addition to backbone chemotherapy consisting of R-CHOP or polatuzumab vedotin-RCHP for younger patients with higher-risk Diffuse Large B-cell Lymphoma or High Grade B-Cell Lymphoma.

Conditions

Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma

Keywords

DLBCL; HGBL

Outcome Measures

Primary Outcomes (3)

• To assess safety of the combination of glofitamab and R-CHOP or pola-RCHP according to number of participants with treatment-related adverse events

  From start of treatment till the end of study, assessed up to approximately 60 months

• To evaluate the Relative Dose Intensity (RDI) of the chemotherapy backbone

  From start of study treatment till the end of study treatment, assessed up to approximately 12 months

• To evaluate the rates of early chemotherapy discontinuation

  From start of study treatment till the end of study treatment, assessed up to approximately 12 months

Secondary Outcomes (5)

• To estimate the proportion of patients achieving a complete response (CR) after cycles 2, 4 and at end of induction treatment (6 cycles) of the novel combination therapy according to Lugano 2014 criteria

  Up to approximately 6 months (each cycle is 21 days)

• To estimate overall response rate (ORR)

  Up to approximately 6 months (each cycle is 21 days)

• To describe progression free survival (PFS)

  From first dose of chemotherapy induction to first date of objectively documented progressive disease or date of death of any cause, whichever occurs first, assessed up to approximately 60 months

• To describe the duration of response (DoR) measured in the subset of patients who achieved CR or PR

  Time from the first documented disease response to the date of progressive disease or death, whichever occurs first, assessed up to approximately 60 months

• Overall survival (OS) as defined as the time from first dose of chemotherapy induction to the date of death from any cause

  From first dose of chemotherapy induction to the date of death from any cause, assessed up to approximately 60 months

Other Outcomes (2)

• Correlation between circulating tumour DNA detection and response (CR and ORR)

  From start of treatment till end of study assessed up to 60 months

• Comparison of efficacy (rates of CR, ORR, DOR, PFS and OS) between the two study arms

  From start of treatment till end of study assessed up to 60 months

Study Arms (2)

Glofitamab plus R-CHOP

EXPERIMENTAL

Participants will receive treatment in 21 day cycles consisting of R-CHOP in cycle 1, followed by R-CHOP plus glofitamab for cycles 2-6, and two cycles of glofitamab monotherapy consolidation. Patients may also receive high-dose methotrexate CNS prophylaxis at investigator discretion.

Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisolone; Drug: Glofitamab

Glofitamab plus polatuzumab vedotin-RCHP

EXPERIMENTAL

Participants will receive treatment in 21 day cycles consisting of R-CHOP in cycle 1, followed by polatuzumab vedotin-RCHP plus glofitamab for cycles 2-6, and two cycles of glofitamab monotherapy consolidation. Patients may also receive high-dose methotrexate CNS prophylaxis at investigator discretion.

Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisolone; Drug: Glofitamab; Drug: Polatuzumab vedotin

Interventions

Rituximab DRUG

Rituximab 375 mg/m\^2 administered by IV infusion on Day 1 of every 21-day cycle

Glofitamab plus R-CHOP; Glofitamab plus polatuzumab vedotin-RCHP

Cyclophosphamide DRUG

Cyclophosphamide 750mg/m\^2 administered by IV infusion on Day 1 of every 21-day cycle

Glofitamab plus R-CHOP; Glofitamab plus polatuzumab vedotin-RCHP

Doxorubicin DRUG

Doxorubicin 50mg/m\^2 administered by IV infusion on Day 1 of every 21-day cycle

Glofitamab plus R-CHOP; Glofitamab plus polatuzumab vedotin-RCHP

Vincristine DRUG

Vincristine 1.4mg/m\^2 administered by IV infusion on Day 1 of every 21-day cycle

Glofitamab plus R-CHOP

Prednisolone DRUG

Prednisolone 100mg orally on Days 1-5 of every 21-day cycle

Glofitamab plus R-CHOP; Glofitamab plus polatuzumab vedotin-RCHP

Glofitamab DRUG

Glofitamab will be administered by IV infusion as per the schedule specified in the respective arm

Also known as: RO7082859, CD20-TCB

Glofitamab plus R-CHOP; Glofitamab plus polatuzumab vedotin-RCHP

Polatuzumab vedotin DRUG

Polatuzumab 1.8mg/kg administered by IV infusion on Day 1 of every 21-day cycle

Glofitamab plus polatuzumab vedotin-RCHP

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18yo and ≤65yo at the time of signing consent
• Have a histologically confirmed diagnosis of one of the following, according to the 2016 WHO classification:
• DLBCL, NOS or DLBCL arising as a result of transformation of an indolent lymphoma
• HGBL, NOS
• HGBL with rearrangements of MYC and BCL2 and/or BCL6
• For DLBCL, and HGBL, NOS meets one of the following risk criteria:
• a. NCCN-IPI of ≥4 or IPI ≥3 (appendix 1 and 3)
• Considered fit for 6 cycles of full dose R-CHOP chemotherapy, as per the Investigator
• ECOG performance status (appendix 5) of:
• inclusive or 3 if directly attributable to lymphoma for patients entering the trial prior to cycle 1 of R-CHOP
• inclusive for patients entering the trial at cycle 2
• Patients must be treatment-naïve or have received a maximum of one cycle of full-dose R-CHOP chemotherapy (with or without a steroid pre-phase)
• Able to provide an archival pre-treatment biopsy.
• Have measurable disease on a pre-chemotherapy PET/CT, defined as at least one bi-dimensionally measurable nodal lesion of \>1.5cm in longest dimension, or at least one bi-dimensionally measurable extranodal lesion of \>1.0cm in longest dimension
• Life expectancy (in the opinion of the Investigator) of ≥ 18 weeks

You may not qualify if:

• Inability to comply with protocol mandated hospitalisations and restrictions
• Prior systemic treatment of an underlying indolent lymphoma with an anthracycline-containing regimen
• Richter's syndrome
• Patients with known CNS involvement by lymphoma
• With the exception of rituximab, any prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immuno-conjugates, antibody-drug conjugates, immune/cytokines, and monoclonal antibodies within 4 weeks or five half-lives of the drug, whichever is shorter, before the first dose of study drug
• With the exception of CHOP used as a first cycle of lymphoma treatment, any chemotherapeutic agent, or treatment with any other investigational agent within 4 weeks prior to study treatment
• Prior solid organ transplantation
• Prior autologous or allogeneic stem cell transplantation
• A history of treatment-emergent immune related AEs associated with prior immunotherapeutic agents
• Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Note: patients with a history of stroke who have not experienced a stroke or transient ischaemic attack in the past 2 years are allowed
• Note: patients with a history of epilepsy who have not experienced a seizure in the past 2 years are allowed, so long as continuation of any ongoing established pharmacologic treatment is not contraindicated
• Past history of confirmed progressive multifocal leukoencephalopathy
• Past history of chronic active EBV or HLH
• Major surgery or significant traumatic injury \<28 days prior to study treatment or anticipation of the need for major surgery during study treatment

Sponsors & Collaborators

• Peter MacCallum Cancer Centre, Australia: lead
• Hoffmann-La Roche: collaborator

Study Sites (15)

Concord Repatriation General Hospital

Camperdown, New South Wales, 2050, Australia

Location

St Vincent's Public Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Princess Alexander Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Barwon Health

Geelong, Victoria, 3220, Australia

Location

Cabrini Hospital

Malvern, Victoria, 3144, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

St Vincent's Hospital Melbourne

Melbourne, Victoria, 3065, Australia

Location

Alfred Hospital

Melbourne, Victoria, Australia

Location

Epworth Healthcare

Melbourne, Victoria, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Related Publications (1)

• Minson A, Verner E, Giri P, Butler J, Janowski W, Cheah CY, Ratnasingam S, Wong SM, Ku M, Hertzberg M, Herbert K, Hamad N, Yannakou CK, Swain F, Neeson P, Steiner TM, Saghebi J, Blombery P, Hunter SM, Robertson M, Lau LS, Bennett R, Harrop S, Xie J, Seymour JF, Dickinson MJ. Glofitamab Combined With Pola-R-CHP or R-CHOP as First Therapy in Younger Patients With High-Risk Large B-Cell Lymphoma: Results From the COALITION Study. J Clin Oncol. 2025 Aug 10;43(23):2595-2605. doi: 10.1200/JCO-25-00481. Epub 2025 Jun 18.

  PMID: 40532125 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisolone; glofitamab; polatuzumab vedotin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Michael Dickinson

  Peter MacCallum Cancer Centre & Royal Melbourne Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: June 7, 2021
• Study Start: June 29, 2021
• Primary Completion: December 5, 2023
• Study Completion: July 1, 2025
• Last Updated: August 12, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (15)