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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04914741




Registration number
NCT04914741
Ethics application status
Date submitted
24/05/2021
Date registered
7/06/2021

Titles & IDs
Public title
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)
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)
Secondary ID [1] 0 0
20/047
Universal Trial Number (UTN)
Trial acronym
COALITION
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse Large B Cell Lymphoma 0 0
High-grade B-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rituximab
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Vincristine
Treatment: Drugs - Prednisolone
Treatment: Drugs - Glofitamab
Treatment: Drugs - Polatuzumab vedotin

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.

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.


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

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

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

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

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

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

Treatment: Drugs: Polatuzumab vedotin
Polatuzumab 1.8mg/kg administered by IV infusion on Day 1 of every 21-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To assess safety of the combination of glofitamab and R-CHOP or pola-RCHP according to number of participants with treatment-related adverse events
Timepoint [1] 0 0
From start of treatment till the end of study, assessed up to approximately 60 months
Primary outcome [2] 0 0
To evaluate the Relative Dose Intensity (RDI) of the chemotherapy backbone
Timepoint [2] 0 0
From start of study treatment till the end of study treatment, assessed up to approximately 12 months
Primary outcome [3] 0 0
To evaluate the rates of early chemotherapy discontinuation
Timepoint [3] 0 0
From start of study treatment till the end of study treatment, assessed up to approximately 12 months
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Up to approximately 6 months (each cycle is 21 days)
Secondary outcome [2] 0 0
To estimate overall response rate (ORR)
Timepoint [2] 0 0
Up to approximately 6 months (each cycle is 21 days)
Secondary outcome [3] 0 0
To describe progression free survival (PFS)
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
To describe the duration of response (DoR) measured in the subset of patients who achieved CR or PR
Timepoint [4] 0 0
Time from the first documented disease response to the date of progressive disease or death, whichever occurs first, assessed up to approximately 60 months
Secondary outcome [5] 0 0
Overall survival (OS) as defined as the time from first dose of chemotherapy induction to the date of death from any cause
Timepoint [5] 0 0
From first dose of chemotherapy induction to the date of death from any cause, assessed up to approximately 60 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2025
Actual
Sample size
Target
Accrual to date
Final
80
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Camperdown
Recruitment hospital [2] 0 0
St Vincent's Public Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [4] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [5] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [6] 0 0
Princess Alexander Hospital - Woolloongabba
Recruitment hospital [7] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [8] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [9] 0 0
Barwon Health - Geelong
Recruitment hospital [10] 0 0
Cabrini Hospital - Malvern
Recruitment hospital [11] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [12] 0 0
St Vincent's Hospital Melbourne - Melbourne
Recruitment hospital [13] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [14] 0 0
Epworth Healthcare - Melbourne
Recruitment hospital [15] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2298 - Newcastle
Recruitment postcode(s) [4] 0 0
2031 - Randwick
Recruitment postcode(s) [5] 0 0
4029 - Herston
Recruitment postcode(s) [6] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [7] 0 0
5000 - Adelaide
Recruitment postcode(s) [8] 0 0
3128 - Box Hill
Recruitment postcode(s) [9] 0 0
3220 - Geelong
Recruitment postcode(s) [10] 0 0
3144 - Malvern
Recruitment postcode(s) [11] 0 0
3000 - Melbourne
Recruitment postcode(s) [12] 0 0
3065 - Melbourne
Recruitment postcode(s) [13] 0 0
- Melbourne
Recruitment postcode(s) [14] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Hoffmann-La Roche
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Dickinson
Address 0 0
Peter MacCallum Cancer Centre & Royal Melbourne Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04914741