InformationClinical trials have complex eligibility criteria.
Always talk to your clinician about you’re interest in participating in a trial.
Learn why

Optimise reading forHealth ProfessionalsPatients

Closed (no longer recruiting)Last updated: 7 February 2024

COALITION: This Phase I/II trial is trying to understand how safe and tolerable a targeted therapy drug (glofitamab) is in combination with chemotherapy in people with higher-risk Diffuse Large B-Cell Lymphoma or High Grade B-Cell LymphomaA Multicentre Trial of Frontline R-CHOP/Pola-RCHP and Glofitamab in Younger, Higher Risk Patients With Diffuse Large B Cell Lymphoma (DLBCL)

Clinical summary

Summary

This randomised trial has two experimental arms.

In Experimental Arm 1, participants will receive 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. Rituximab 375 mg/m^2 will be administered by IV infusion on Day 1 of every 21-day cycle. Cyclophosphamide 750mg/m^2 will be administered by IV infusion on Day 1 of every 21-day cycle. Doxorubicin 50mg/m^2 will be administered by IV infusion on Day 1 of every 21-day cycle. Vincristine 1.4mg/m^2 will be administered by IV infusion on Day 1 of every 21-day cycle. Prednisolone 100mg will be administered orally on Days 1-5 of every 21-day cycle. Glofitamab will be administered by IV infusion as per the schedule specified in the respective arm.

In Experimental Arm 2, participants will receive 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. Rituximab 375 mg/m^2 will be administered by IV infusion on Day 1 of every 21-day cycle. Cyclophosphamide 750mg/m^2 will be administered by IV infusion on Day 1 of every 21-day cycle. Doxorubicin 50mg/m^2 will be administered by IV infusion on Day 1 of every 21-day cycle. Prednisolone 100mg will be administered orally on Days 1-5 of every 21-day cycle. Glofitamab will be administered by IV infusion as per the schedule specified in the respective arm.

Conditions

This trial is treating patients with Diffuse Large B-Cell Lymphoma and High-grade B-Cell lymphoma.

Cancer

Blood Cancers Haematological

Age

People18 - 65

Phase

I/II

Trial Acronym

COALITION

More information

Trial Identifiers

Use the hyperlinks, where available to access additional clinical trial information.

Trial sponsor

Hoffmann-La Roche, National Health Service Blood & Transplant

Scientific Title

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

Eligibility

Inclusion

  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-naive 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

  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.

Inclusion

  • You are able to swallow medication by mouth.
  • You have been diagnosed with cancer, but have not received any treatment.
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

Participating hospitals

+ Show non-recruiting hospitals

Closed hospitals

InformationTell us if you find this trial availability is not accurate.Report inaccuracy

Get Support

Example

Cancer Connect

Speak with someone who has cancer clinical trial experience.

Learn more

Example

Cancer Council’s cancer nurses

If you need cancer information and practical support for yourself, a carer, family or friend, contact Cancer Council’s experienced cancer nurses on 131120.

Learn more

Example

Information for family, friends and carers

When you are considering a cancer clinical trial, it is a good idea to discuss it with your family, friends or carers.

Learn more

Victorian Cancer Registry Victorian Government

The Victorian Cancer Trials Link is supported by the Victorian Government through the Victorian Cancer Agency.

RAP

Cancer Council Victoria would like to acknowledge the traditional custodians of the land on which we live and work. We would also like to pay respect to the elders past and present and extend that respect to all other Aboriginal people.