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Diffuse Large B Cell LymphomaPhase 1/2COALITIONNCT04914741

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)

A Phase 1/2 study testing Rituximab, Cyclophosphamide and Doxorubicin in people with Diffuse Large B Cell Lymphoma and High-grade B-cell Lymphoma, run by Peter MacCallum Cancer Centre, Australia at 15 sites in Australia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Rituximab, Cyclophosphamide and Doxorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
15 sitesAustralia
Study dates
29 Jun 2021to Jul 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 21Show fewer
  • 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:
  • 0-2 inclusive or 3 if directly attributable to lymphoma for patients entering the trial prior to cycle 1 of R-CHOP
  • 0-1 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
  • Adequate haematological function
  • Adequate renal function
  • Adequate hepatic function
  • Negative serologic or PCR test results for active acute or chronic HBV infection.
  • Non-haematological AEs from prior anti-cancer therapy must have resolved to Grade ≤1 (with the exception of alopecia and inclusion criteria 10-12)
  • Negative test results for HCV and HIV.

Who cannot join

  • 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
Show all 34Show fewer
  • 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
  • Significant cardiovascular disease, defined as:
  • A left ventricular ejection fraction (as determined by nuclear gated blood pool scan or echocardiogram) <50%
  • Myocardial infarction or unstable angina within the past 6 months
  • Unstable arrhythmia
  • Any other cardiac illness that, in the opinion of the Investigator or CPI, makes the patient unsuitable for anthracycline containing therapy
  • Significant pulmonary disease, including but not limited to clinically significant obstructive pulmonary disease or history of bronchospasm
  • Current grade >1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease
  • Known clinically significant liver disease, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
  • 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
  • History of other active malignancy within 5 years prior to registration, with the exception of:
  • FL or MZL, previously untreated, or treated with no more than one line of therapy which must not have contained an anthracycline
  • Basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix
  • Prior malignancy treated with a curative intent that has remained in remission without treatment for ≥2 years prior to registration
  • Patients with known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of the nail beds) at registration
  • Note: Patients with latent tuberculosis are excluded
  • 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
  • Major contraindication to any of the individual components of the chemotherapy backbone (R, C, H, O, Polatuzumab vedotin, prednisolone)
  • Patients who are pregnant or breastfeeding
  • Other protocol-defined inclusion and exclusion criteria may apply.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

Australia15 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Box Hill Hospital

    Box Hill, Victoria, 3128

  • Concord Repatriation General Hospital

    Camperdown, New South Wales, 2050

  • St Vincent's Public Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • Barwon Health

    Geelong, Victoria, 3220

  • Royal Brisbane and Women's Hospital

    Herston, Queensland, 4029

  • Cabrini Hospital

    Malvern, Victoria, 3144

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

  • St Vincent's Hospital Melbourne

    Melbourne, Victoria, 3065

  • Alfred Hospital

    Melbourne, Victoria

  • Epworth Healthcare

    Melbourne, Victoria

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • Calvary Mater Newcastle

    Newcastle, New South Wales, 2298

  • Prince of Wales Hospital

    Randwick, New South Wales, 2031

  • Princess Alexander Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

About this study

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)

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.

Keywords
DLBCL, HGBL
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

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

  • CyclophosphamideDrug

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

  • DoxorubicinDrug

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

  • VincristineDrug

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

  • PrednisoloneDrug

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

  • GlofitamabDrug

    Also called RO7082859, CD20-TCB

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

  • Polatuzumab vedotinDrug

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

Study groups in NCT04914741
Study groupRoleWhat they receive
Glofitamab plus R-CHOPExperimentalParticipants 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.
Receives: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisolone; Drug: Glofitamab
Glofitamab plus polatuzumab vedotin-RCHPExperimentalParticipants 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.
Receives: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisolone; Drug: Glofitamab; Drug: Polatuzumab vedotin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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

    Measured: 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

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

Secondary outcomes (5)

  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

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

  2. To estimate overall response rate (ORR)

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

  3. To describe progression free survival (PFS)

    Measured: 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

    Measured: 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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2021
  2. Study start29 Jun 2021
  3. Primary completion5 Dec 2023
  4. Study completionJul 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04914741
Sponsor's protocol ID
20/047
Acronym
COALITION
Status last verified
Aug 2024
First submitted
24 May 2021
Last updated
12 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40532125

  • Duell J, Westin J. The future of immunotherapy for diffuse large B-cell lymphoma. Int J Cancer. 2025 Jan 15;156(2):251-261. doi: 10.1002/ijc.35156. Epub 2024 Sep 25.

    PubMed 39319495

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Rituximab, Cyclophosphamide and Doxorubicin in people with Diffuse Large B Cell Lymphoma and High-grade B-cell Lymphoma, run by Peter MacCallum Cancer Centre, Australia at 15 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 12 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04914741, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2024.

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