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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) (COALITION)

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ClinicalTrials.gov Identifier: NCT04914741
Recruitment Status : Recruiting
First Posted : June 7, 2021
Last Update Posted : April 22, 2022
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Peter MacCallum Cancer Centre, Australia

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.

Condition or disease Intervention/treatment Phase
Diffuse Large B Cell Lymphoma High-grade B-cell Lymphoma Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisolone Drug: Glofitamab Drug: Polatuzumab vedotin Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicentre Trial of Frontline R-CHOP/Pola-RCHP and Glofitamab in Younger, Higher Risk Patients With Diffuse Large B Cell Lymphoma (DLBCL)
Actual Study Start Date : June 29, 2021
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : July 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Glofitamab plus R-CHOP
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
Rituximab 375 mg/m^2 administered by IV infusion on Day 1 of every 21-day cycle

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

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

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

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

Drug: Glofitamab
Glofitamab will be administered by IV infusion as per the schedule specified in the respective arm
Other Names:
  • RO7082859
  • CD20-TCB

Experimental: Glofitamab plus polatuzumab vedotin-RCHP
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
Rituximab 375 mg/m^2 administered by IV infusion on Day 1 of every 21-day cycle

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

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

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

Drug: Glofitamab
Glofitamab will be administered by IV infusion as per the schedule specified in the respective arm
Other Names:
  • RO7082859
  • CD20-TCB

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




Primary Outcome Measures :
  1. To assess safety of the combination of glofitamab and R-CHOP or pola-RCHP according to number of participants with treatment-related adverse events [ Time Frame: From start of treatment till the end of study, assessed up to approximately 60 months ]
  2. To evaluate the Relative Dose Intensity (RDI) of the chemotherapy backbone [ Time Frame: From start of study treatment till the end of study treatment, assessed up to approximately 12 months ]
  3. To evaluate the rates of early chemotherapy discontinuation [ Time Frame: From start of study treatment till the end of study treatment, assessed up to approximately 12 months ]

Secondary Outcome Measures :
  1. 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 [ Time Frame: Up to approximately 6 months (each cycle is 21 days) ]
  2. To estimate overall response rate (ORR) [ Time Frame: Up to approximately 6 months (each cycle is 21 days) ]
  3. To describe progression free survival (PFS) [ Time Frame: 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 ]
  4. To describe the duration of response (DoR) measured in the subset of patients who achieved CR or PR [ Time Frame: Time from the first documented disease response to the date of progressive disease or death, whichever occurs first, assessed up to approximately 60 months ]
  5. Overall survival (OS) as defined as the time from first dose of chemotherapy induction to the date of death from any cause [ Time Frame: From first dose of chemotherapy induction to the date of death from any cause, assessed up to approximately 60 months ]

Other Outcome Measures:
  1. Correlation between circulating tumour DNA detection and response (CR and ORR) [ Time Frame: From start of treatment till end of study assessed up to 60 months ]
  2. Comparison of efficacy (rates of CR, ORR, DOR, PFS and OS) between the two study arms [ Time Frame: From start of treatment till end of study assessed up to 60 months ]


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:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥18yo and ≤65yo at the time of signing consent
  2. Have a histologically confirmed diagnosis of one of the following, according to the 2016 WHO classification:

    1. DLBCL, NOS or DLBCL arising as a result of transformation of an indolent lymphoma
    2. HGBL, NOS
    3. HGBL with rearrangements of MYC and BCL2 and/or BCL6
  3. For DLBCL, and HGBL, NOS meets one of the following risk criteria:

    a. NCCN-IPI of ≥4 or IPI ≥3 (appendix 1 and 3)

  4. Considered fit for 6 cycles of full dose R-CHOP chemotherapy, as per the Investigator
  5. ECOG performance status (appendix 5) of:

    1. 0-2 inclusive or 3 if directly attributable to lymphoma for patients entering the trial prior to cycle 1 of R-CHOP
    2. 0-1 inclusive for patients entering the trial at cycle 2
  6. 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)
  7. Able to provide an archival pre-treatment biopsy.
  8. 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
  9. Life expectancy (in the opinion of the Investigator) of ≥ 18 weeks
  10. Adequate haematological function
  11. Adequate renal function
  12. Adequate hepatic function
  13. Negative serologic or PCR test results for active acute or chronic HBV infection.
  14. Non-haematological AEs from prior anti-cancer therapy must have resolved to Grade ≤1 (with the exception of alopecia and inclusion criteria 10-12)
  15. Negative test results for HCV and HIV.

Exclusion Criteria:

  1. Inability to comply with protocol mandated hospitalisations and restrictions
  2. Prior systemic treatment of an underlying indolent lymphoma with an anthracycline-containing regimen
  3. Richter's syndrome
  4. Patients with known CNS involvement by lymphoma
  5. 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
  6. 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
  7. Prior solid organ transplantation
  8. Prior autologous or allogeneic stem cell transplantation
  9. A history of treatment-emergent immune related AEs associated with prior immunotherapeutic agents
  10. Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease

    1. Note: patients with a history of stroke who have not experienced a stroke or transient ischaemic attack in the past 2 years are allowed
    2. 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
  11. Past history of confirmed progressive multifocal leukoencephalopathy
  12. Past history of chronic active EBV or HLH
  13. Major surgery or significant traumatic injury <28 days prior to study treatment or anticipation of the need for major surgery during study treatment
  14. Significant cardiovascular disease, defined as:

    1. A left ventricular ejection fraction (as determined by nuclear gated blood pool scan or echocardiogram) <50%
    2. Myocardial infarction or unstable angina within the past 6 months
    3. Unstable arrhythmia
    4. Any other cardiac illness that, in the opinion of the Investigator or CPI, makes the patient unsuitable for anthracycline containing therapy
  15. Significant pulmonary disease, including but not limited to clinically significant obstructive pulmonary disease or history of bronchospasm
  16. Current grade >1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease
  17. Known clinically significant liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
  18. Administration of a live, attenuated vaccine within 4 weeks before study treatment note: influenza vaccination should be given during influenza season only. Patients must not receive live, attenuated influenza vaccine at any time during the study treatment period
  19. History of other active malignancy within 5 years prior to registration, with the exception of:

    1. FL or MZL, previously untreated, or treated with no more than one line of therapy which must not have contained an anthracycline
    2. Basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix
    3. Prior malignancy treated with a curative intent that has remained in remission without treatment for ≥2 years prior to registration
  20. Patients with known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of the nail beds) at registration

    a. Note: Patients with latent tuberculosis are excluded

  21. Other significant life-threatening illness or medical condition which, in the Investigator's opinion, could compromise the patient's safety, interfere with absorption or metabolism of study drug, affect compliance with the protocol or interpretation of results, or put the study outcomes at undue risk
  22. Major contraindication to any of the individual components of the chemotherapy backbone (R, C, H, O, Polatuzumab vedotin, prednisolone)
  23. Patients who are pregnant or breastfeeding

Other protocol-defined inclusion and exclusion criteria may apply.


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): NCT04914741


Contacts
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Contact: Michael Dickinson +61385597858 michael.dickinson@petermac.org
Contact: Adrian Minson +61385598309 adrian.minson@petermac.org

Locations
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Australia, New South Wales
Concord Repatriation General Hospital Recruiting
Camperdown, New South Wales, Australia, 2050
Contact: Emma Verner       Emma.Verner@health.nsw.gov.au   
St Vincent's Public Hospital Sydney Recruiting
Darlinghurst, New South Wales, Australia, 2010
Contact: Nada Hamad       Nada.Hamad@svha.org.au   
Calvary Mater Newcastle Recruiting
Newcastle, New South Wales, Australia, 2298
Contact: Wojt Janowski       Wojt.Janowski@calvarymater.org.au   
Prince of Wales Hospital Recruiting
Randwick, New South Wales, Australia, 2031
Contact: Mark Hertzberg       Mark.Hertzberg@health.nsw.gov.au   
Australia, Queensland
Royal Brisbane and Women's Hospital Recruiting
Herston, Queensland, Australia, 4029
Contact: Jason Butler       Jason.Butler@health.qld.gov.au   
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Pratyush Giri       Pratyush.Giri@sa.gov.au   
Australia, Victoria
Barwon Health Recruiting
Geelong, Victoria, Australia, 3220
Contact: Sumita Ratnasingam       SUMITA.RATNASINGAM@barwonhealth.org.au   
Cabrini Hospital Recruiting
Malvern, Victoria, Australia, 3144
Contact: Kirsten Herbert       kirsten.herbert@petermac.org   
Peter MacCallum Cancer Centre Recruiting
Melbourne, Victoria, Australia, 3000
Contact: Adrian Minson       adrian.minson@petermac.org   
St Vincent's Hospital Melbourne Recruiting
Melbourne, Victoria, Australia, 3065
Contact: Matthew Ku       matthew.ku@svha.org.au   
Alfred Hospital Recruiting
Melbourne, Victoria, Australia
Contact: Shu Min Wong       shu.wong@alfred.org.au   
Epworth Healthcare Recruiting
Melbourne, Victoria, Australia
Contact: Costas Yannakou       costas.yannakou@epworth.org.au   
Australia, Western Australia
Sir Charles Gairdner Hospital Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Chan Cheah       Chan.Cheah@health.wa.gov.au   
Sponsors and Collaborators
Peter MacCallum Cancer Centre, Australia
Hoffmann-La Roche
Investigators
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Principal Investigator: Michael Dickinson Peter MacCallum Cancer Centre & Royal Melbourne Hospital
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Responsible Party: Peter MacCallum Cancer Centre, Australia
ClinicalTrials.gov Identifier: NCT04914741    
Other Study ID Numbers: 20/047
First Posted: June 7, 2021    Key Record Dates
Last Update Posted: April 22, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Peter MacCallum Cancer Centre, Australia:
DLBCL
HGBL
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Prednisolone
Cyclophosphamide
Rituximab
Doxorubicin
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic