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)

NCT ID: NCT04914741

Last Updated: 2024-08-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-29
• Study Completion Date: 2025-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Doxorubicin

Intervention Type: DRUG

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

Vincristine

Intervention Type: DRUG

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

Prednisolone

Intervention Type: DRUG

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

Glofitamab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Doxorubicin

Intervention Type: DRUG

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

Prednisolone

Intervention Type: DRUG

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

Glofitamab

Intervention Type: DRUG

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

Polatuzumab vedotin

Intervention Type: DRUG

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

Interventions

Rituximab

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Doxorubicin

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

Intervention Type: DRUG

Vincristine

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

Intervention Type: DRUG

Prednisolone

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

Intervention Type: DRUG

Glofitamab

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

Intervention Type: DRUG

Polatuzumab vedotin

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

Intervention Type: DRUG

Other Intervention Names

RO7082859; CD20-TCB

Eligibility 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.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Peter MacCallum Cancer Centre, Australia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Dickinson

Role: PRINCIPAL_INVESTIGATOR

Peter MacCallum Cancer Centre & Royal Melbourne Hospital

Locations

Concord Repatriation General Hospital

Camperdown, New South Wales, Australia

St Vincent's Public Hospital Sydney

Darlinghurst, New South Wales, Australia

Calvary Mater Newcastle

Newcastle, New South Wales, Australia

Prince of Wales Hospital

Randwick, New South Wales, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Princess Alexander Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Barwon Health

Geelong, Victoria, Australia

Cabrini Hospital

Malvern, Victoria, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

St Vincent's Hospital Melbourne

Melbourne, Victoria, Australia

Alfred Hospital

Melbourne, Victoria, Australia

Epworth Healthcare

Melbourne, Victoria, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Countries

Australia

References

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.

Reference Type: DERIVED

PMID: 40532125 (View on PubMed)

Other Identifiers

20/047

Identifier Type: -

Identifier Source: org_study_id