Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001529831
Ethics application status
Approved
Date submitted
20/06/2021
Date registered
10/11/2021
Date last updated
31/05/2024
Date data sharing statement initially provided
10/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
NHL35: A study of Pembrolizumab And Chemo-Immunotherapy as FIrst-line therapy for patients with primary mediastinal B-Cell lymphoma.
Scientific title
NHL35 -An Australasian Leukaemia and Lymphoma Group open label phase II study of the effect of of R-CHOP in combination with pembrolizumab in patients with newly diagnosed primary mediastinal B Cell Lymphoma (PMBL).
Secondary ID [1] 304538 0
None
Universal Trial Number (UTN)
Trial acronym
PACIFIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary mediastinal B-cell lymphoma 322410 0
Condition category
Condition code
Cancer 320068 320068 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The trial is a Phase II trial.

Patients will receive the following treatment

Cycle 1 and 2: R-pembro ‘window’ (21-day cycle)
* Rituximab 375mg/m2 Intravenous Infusion on Day 1
* Pembrolizumab 200mg Intravenous Infusion on Day 1

Cycle 3- to 8: ‘Induction’ (21-day cycle) -
* Rituximab 375mg/m2 Intravenous Infusion on Day 1
* Cyclophosphamide 750mg/m2 Intravenous Infusion on Day 1
* Doxorubicin 50mg/m2 Intravenous Infusion on Day 1
* Vincristine 1.4mg/m2 Intravenous Infusion on Day 1 capped at 2mg
* Prednisolone 100mg oral tablet on Day 1 to Day 5
* Pembrolizumab 200mg Intravenous Infusion on Day 1

Cycle 9-17: Pembrolizumab ‘Consolidation’ (21-day cycle)
* Pembrolizumab 200mg Intravenous Infusion on D1

Upon completion of the cycle, the next cycle will commence.
Intervention code [1] 320889 0
Treatment: Drugs
Comparator / control treatment
No control
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327941 0
Percentage of patients achieving Event Free Survival . Event Free Survival will be assessed by medical reports and assessments of patients response.
Timepoint [1] 327941 0
Measured from first dose of treatment to completion of treatment at 18 months
Secondary outcome [1] 397061 0
To evaluate the safety by assessing the number of side effects seen per category of the Common Terminology Criteria for Adverse Events V5. Side effects will be assessed during the patient's regular clinic visit with the treating clinician and blood and urine biochemistry tests.
Timepoint [1] 397061 0
Measured from date of registration to 30 days after administration of the last study treatment.

Eligibility
Key inclusion criteria
1. Subjects aged equal to greater than 18 years at time of enrolment.
2. Able to give informed consent.
3. Clinical and histological diagnosis of PMBL, according to the current World Health Organization classification.
4. No previous treatment for lymphoma including chemotherapy, radiotherapy or other investigational drug.
5. Eastern Collaborative Oncology Group performance status 0-<=1.
6. Platelets >= 100x109/l; neutrophils >= 1.0x109/l at the time of study entry.
7. Creatinine clearance >=30ml/min (calculated according to MRDR or Cockcroft Gault equation)
8. Total bilirubin less than or equal to 1.5 × ULN, AST and ALT less or equal to 2..5 x ULN
9. LVEF greater or equal to 45%
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known hypersensitivity to any study medication, including previous grade >=3 hypersensitivity reactions to monoclonal antibody therapy.
2. Active autoimmune disease; requiring immunosuppressive therapy within 6 months of study entry.
3. Other lymphoma subtypes, other than PMBL.
4. Central nervous system, meningeal or spinal cord involvement by lymphoma.
5. Prior therapy with any antibody or drug targeting T-cell coregulatory proteins (immune checkpoints) such as PD-1, PD-L1, or cytotoxic T-lymphocyte antigen-4 (CTLA-4).
6. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. – Please note that a short course of steroids (e.g. Oral Prednisolone 1mg/kg daily or equivalent for <=7 days duration) will be permitted if indicated for lymphoma symptoms (but should be avoided if possible)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/12/2023
Actual
13/01/2023
Date of last participant enrolment
Anticipated
31/05/2025
Actual
Date of last data collection
Anticipated
31/05/2028
Actual
Sample size
Target
35
Accrual to date
17
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,WA,VIC
Recruitment hospital [1] 26623 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 26624 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 26625 0
Westmead Hospital - Westmead
Recruitment hospital [4] 26626 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 26627 0
Box Hill Hospital - Box Hill
Recruitment hospital [6] 26628 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 26629 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [8] 26630 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [9] 26631 0
Gold Coast University Hospital - Southport
Recruitment postcode(s) [1] 42664 0
2050 - Camperdown
Recruitment postcode(s) [2] 42665 0
2145 - Westmead
Recruitment postcode(s) [3] 42666 0
2170 - Liverpool
Recruitment postcode(s) [4] 42670 0
3000 - Melbourne
Recruitment postcode(s) [5] 42667 0
3128 - Box Hill
Recruitment postcode(s) [6] 42671 0
4215 - Southport
Recruitment postcode(s) [7] 42668 0
5000 - Adelaide
Recruitment postcode(s) [8] 42669 0
5042 - Bedford Park
Recruitment postcode(s) [9] 42663 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 23796 0
New Zealand
State/province [1] 23796 0

Funding & Sponsors
Funding source category [1] 308904 0
Other Collaborative groups
Name [1] 308904 0
Australasian Leukaemia and Lymphoma Group
Country [1] 308904 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Lymphoma and Leukaemia Group
Address
ALLG
35 Elizabeth Street
Richmond Vic
3121
Country
Australia
Secondary sponsor category [1] 309827 0
None
Name [1] 309827 0
Address [1] 309827 0
Country [1] 309827 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308803 0
Sir Charles Gairdner Human Research Ethics Committee
Ethics committee address [1] 308803 0
Sir Charles Gairdner Hospital
Level 2, A Block, QEII Medical Centre
Hospital Avenue
Nedlands WA 6009
Ethics committee country [1] 308803 0
Australia
Date submitted for ethics approval [1] 308803 0
31/01/2022
Approval date [1] 308803 0
29/07/2022
Ethics approval number [1] 308803 0
RGS0000005286

Summary
Brief summary
This trial is for patients with primary mediastinal B-cell lymphoma (PMBL) and is evaluating if combining pembrolizumab with R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) will improve patient outcomes.

All patients will receive the following treatment regimen:

Cycle 1-2: R-pembro ‘window’ (21-day cycle)
* rituximab 375mg/m2 Intravenous Infusion on Day 1
* pembrolizumab 200mg Intravenous Infusion on Day 1

Cycle 3-8: ‘Induction’ (21-day cycle)
* rituximab 375mg/m2 Intravenous Infusion on Day 1
* cyclophosphamide 750mg/m2 Intravenous Infusion on Day 1
*doxorubicin 50mg/m2 Intravenous Infusion on Day 1
*vincristine 1.4mg/m2 Intravenous Infusion on Day 1 capped at 2mg
*prednisolone 100mg oral tablet on Days 1-5
pembrolizumab 200mg Intravenous Infusion on D1

Cycle 9-17: Pembrolizumab ‘Consolidation’ (21-day cycle)
* pembrolizumab 200mg Intravenous Infusion on Day1

Patients will have a PET/CT Scan at the following timepoints
1. After Registration
2. After the "Pembro" phase
3. After the "Induction" phase
4. Patients may have another PET/CT scan at the discretion of their treating physician.

Patients will also have blood samples taken every three weeks whilst receiving treatment.

It is hoped that this study may demonstrate that addition of pembrolizumab to R-CHOP may improve survival in patients with PMBL.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111942 0
Prof Chan Cheah
Address 111942 0
Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA, 6009
Country 111942 0
Australia
Phone 111942 0
+61383739701
Fax 111942 0
Email 111942 0
delaine.smith@allg.org.au
Contact person for public queries
Name 111943 0
Ms Delaine Smith
Address 111943 0
Australasian Leukaemia and Lymphoma Group
35 Elizabeth Street
Richmond
Vic
3121
Country 111943 0
Australia
Phone 111943 0
+61383739701
Fax 111943 0
Email 111943 0
delaine.smith@allg.org.au
Contact person for scientific queries
Name 111944 0
Ms Delaine Smith
Address 111944 0
Australasian Leukaemia and Lymphoma Group
35 Elizabeth Street
Richmond
Vic
3121
Country 111944 0
Australia
Phone 111944 0
+61383739701
Fax 111944 0
Email 111944 0
delaine.smith@allg.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual patient data will not be shared publicly. Aggregate patient data and final results will be presented in the final report


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.