Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000207718
Ethics application status
Approved
Date submitted
17/11/2021
Date registered
7/02/2022
Date last updated
17/04/2024
Date data sharing statement initially provided
7/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of a chemotherapy regime and tislelizumab in elderly patients with Hodgkin Lymphoma
Scientific title
An ALLG phase II study of CHOP And Tislelizumab in elderly patients with Hodgkin Lymphoma - Australasian Leukaemia and Lymphoma Group (ALLG) HD12
Secondary ID [1] 305820 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hodgkin Lymphoma 324332 0
Condition category
Condition code
Cancer 321826 321826 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Summary of treatment regimen

Patients with Early-stage Unfavourable Hodgkin Lymphoma (HL)
• 3 cycles of lead in Tislelizumab
• 4 total cycles Tis-CHOP or mini-CHOP
• Radiation Therapy (RT)

Patients with Advanced stage HL
• 3 cycles of Lead in Tislelizumab
• 6 total cycles of Tis-CHOP/mini-CHOP
• Patients whose response is classified a partial response can either receive RT OR receive 4 doses of Consolidation-Tislelizumab therapy starting 1-3 weeks after the PET-CT scan.

For patients who achieve a complete response (CR), the duration of systemic therapy will be for 21 weeks for early-stage HL or 27 weeks for advanced stage HL.

Patients will be followed for at least 2 years after end of treatment. All patients will be followed until the last patient has 2 years of follow-up post completion of treatment.


Detailed Treatment Plan
Optional pre-phase corticosteroid can be given after the screening PET-CT scan in those with very symptomatic HL. The dose can be up to 75mg of prednisone orally for up to 7 days and must be stopped at least 24 hours prior to tislelizumab.

Immunotherapy Lead In phase:
• Tislelizumab is given at 200mg intravenously (IV) on day 1
• Cycles are every 3 weeks for 3 cycles from cycle 1-3
• A PET-CT scan (PET-CT1) will be conducted 3-4 weeks after cycle 3, day 1 of the Tisleleluzimab lead in phase

Chemotherapy - Immunotherapy phase:
• This treatment phase will commence 4 - 5 weeks after cycle 3 day 1 of the lead in phase
• This treatment phase includes Tislelizumab and chemotherapy backbone of CHOP or mini-CHOP
• Cycles are every 21 days for 4-6 cycles, depending on the treatment stage eg advanced or early stage HL:
• Tislelizumab is given at 200mg intravenously (IV) on day 1
• The CHOP regimen is:
• Doxorubicin 50mg mg/m2 is given IV on day 1
• Vincristine 1.4mg/m2 (capped at 2mg) is given IV on day 1
• Cyclophosphamide 750mg/m2 is given IV on day 1
• Prednisone 40mg/m2 is given orally daily from day 1 to 5

• The mini-CHOP regimen is:
• Doxorubicin 25mg mg/m2 given IV on day 1
• Vincristine 1mg flat dose given IV on day 1
• Cyclophosphamide 400 mg/m2 given IV on day 1
• Prednisone 40mg/m2 given orally on days 1 to 5

For early stage patients, a final PET-CT scan is had at the end of the last treatment cycle to determine response

Immunotherapy Consolidation Phase:
• This treatment phase is only for those patients treated as advanced HL who are in a partial response on their end of treatment PET-CT.
• Tislelizumab 200mg is given IV on day 1
• Cycles are every 3 weeks for 4 cycles.
• A final PET-CT scan is had to determine response

Radiotherapy:
• For early-stage HL should be according to institutional guidelines
• For patients with advanced stage HL, radiotherapy is usually not indicated for those who have achieved a complete response. For those patients in a partial response, RT can be given according to investigator discretion, OR the patient can proceed to immunotherapy consolidation phase with Tislelizumab


Please note the following points:
• Mini-CHOP should be prescribed to all patients over the age of 80 at time of study registration.
• Patients aged 80 or less, should be prescribed CHOP if possible, however mini-CHOP can be prescribed provided there is a clearly documented reason that is communicated to the CI such as a high frailty score (6 or higher) or notable co-morbidities that the local investigator believes may preclude the use of full dose CHOP.
* Patients will be provided with dosing diaries to assist with compliance.
Intervention code [1] 322214 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329582 0
The primary endpoint is complete metabolic response (CMR) of immunotherapy lead in with tislelizumab monotherapy in a dedicated treatment naïve elderly HL population. CMR will be assessed using a PET-CT scan.
Timepoint [1] 329582 0
This endpoint will be assessed when all patients have completed treatment and had their final PET-CT scan. Timing of the PET-CT scan is dependent on the patient's stage of disease and response, and will occur after the end of the last immunotherapy treatment cycle.
Primary outcome [2] 329583 0
The deliverability of immunotherapy lead in with tislelizumab monotherapy in a dedicated treatment naïve elderly HL population will also be assessed. This will be completed by reviewing physical exam and blood markers for adverse events and disease progression (composite primary outcome).
Timepoint [2] 329583 0
This endpoint will be assessed when all patients have completed or withdrawn from treatment.
Secondary outcome [1] 403101 0
The rate of adverse events (AE) will be calculated. AEs will be determined from blood markers and from the patients medical notes.
Timepoint [1] 403101 0
This outcome will be calculated when all patients have completed treatment. Adverse events will be collected at the patients standard of care visits from treatment commencement to 2 years after therapy completion.
Secondary outcome [2] 403102 0
The overall response rate (ORR) of Tisleluzimab monotherapy will be assessed. This will be completed using response data from the PET-CT scans.
Timepoint [2] 403102 0
This endpoint will be assessed when all patients have completed treatment and had their final PET-CT scan. Timing of the PET-CT scan is dependent on the patient's stage of disease and response, and will occur after the end of the last immunotherapy treatment cycle.
Secondary outcome [3] 403103 0
The CMR rate at the end of cycle 2 of the immunotherapy-chemotherapy phase will be assessed. PET-CT scan will be used to determine CMR.
Timepoint [3] 403103 0
This endpoint will be completed when all patients have completed all treatment.. Results will be taken from the PET-CT scan undertaken after the immunotherapy-chemotherapy phase.
Secondary outcome [4] 403107 0
The overall response rate (ORR) will be assessed at the end the immunotherapy and chemotherapy phases. ORR will be assessed using a PET-CT.
Timepoint [4] 403107 0
This endpoint will be analysed once all patients have completed treatment. Results will be taken from the PET-CT scan undertaken after the immunotherapy-chemotherapy phase.
Secondary outcome [5] 403108 0
Overall survival will be analysed using data from patient clinic visits.
Timepoint [5] 403108 0
This will calculated at 1 and 2 years after therapy completion.
Secondary outcome [6] 403109 0
Progression Free Survival will be calculated. This endpoint will use the PET-CT results to assess progression.
Timepoint [6] 403109 0
This will be assessed at 1 and 2 years after therapy has been completed.
Secondary outcome [7] 403110 0
Patient reported outcome (PRO) - CTCAE score will be assessed in conjunction with the adverse events data. The PRO-CTCAE scores will be a questionnaire and the AE data will be collected from physical exams and blood markers.
Timepoint [7] 403110 0
This will be completed for all patients at baseline and after all patients have completed therapy. Adverse events will be collected at the patients standard of care visits from treatment commencement to 2 years after therapy completion.

Eligibility
Key inclusion criteria
1. Histologically confirmed diagnosis of classical HL according to the current World Health Organisation (WHO). Diagnosis must be made on a core or excision biopsy of a suitable target lesion.
2. Aged 61 years or older
3. Clinical stage IIA (unfavourable as per German Hodgkin Study Group (GHSG) criteria) to IVB
4. Has provided written informed consent
5. Life expectancy at least 3 months
6. Men who are sexually active with women of child-bearing potential must use any highly effective contraceptive method during the study (failure rate less than 1% per year) and for a period of 120 days after the last dose of therapy
7. PET-CT avid disease at baseline.
8. Adequate haematological, renal, hepatic and cardiac function at Screening as defined by:
a. ANC (segs + bands) equal to or greater than 1.0 x 10^9/L
b. Platelet count equal to or greater than 75 x 10^9/L (or 50 if bone marrow is involved)
c. Total bilirubin equal to or less than 1.5 x ULN (unless rise in bilirubin is due to Gilbert’s syndrome or of non-hepatic origin
d. ALT and AST equal to or less than 3 x ULN
e. Creatinine clearance equal to or greater than 30ml / min / 1.73m2
f. LVEF within institutional normal limits (determined either by echocardiography or gated heart pool scan).
9. An ECOG performance status score of 0 or 1 at Screening
Minimum age
61 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Central nervous system involvement
2. Requirement of urgent treatment due to life threatening complications of the disease.
3. Immunosuppressive therapy within the last 2 months, apart from inhaled or topical corticosteroids or systemic corticosteroids at low doses (equal to or greater than 10mg prednisone per day or equivalent)
4. Has active auto-immune disease that has required systemic treatment in the prior 2 years with immunosuppressive agents. Replacement therapy such as thyroxine, insulin or physiological steroid replacement for adrenal or pituitary insufficiency is not considered a form of systemic therapy, and hence patients on these therapies are allowed.
5. History of inflammatory bowel disease or pneumonitis
6. Prior treatments with chemotherapy or radiotherapy within 15 days prior to registration.
7. Prior anthracycline use equivalent to greater than 150mg/m2 of doxorubicin.
8. History of malignancy during the past 2 years except for locally curable cancers, that have had curative surgical treatment. Examples are:
-Treated carcinoma in situ at any site (e.g. cervix, breast)
Adequately treated non melanoma skin cancer
-Superficial bladder cancer, adequately treated with surgical/cauterisation. (BCG treatment is excluded)
-Untreated chronic lymphocytic leukaemia with a less than 50% rise in the lymphocyte count in the preceding 6 months
-Low risk early-stage prostate adenocarcinoma (Gleason score equal to or less than 6).
-Pre-malignant lesions (e.g. monoclonal gammopathy of uncertain significance, monoclonal B cell lymphocytosis) are allowed.
9. Uncontrolled active infection (defined as an infection that requires intravenous anti-microbial treatment,) at the time of first dose of therapy.

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
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/06/2023
Actual
7/08/2023
Date of last participant enrolment
Anticipated
2/08/2027
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
35
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 24328 0
New Zealand
State/province [1] 24328 0

Funding & Sponsors
Funding source category [1] 310169 0
Other Collaborative groups
Name [1] 310169 0
Australasian Leukaemia and Lymphoma Group (ALLG)
Country [1] 310169 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
ALLG
Ground floor, 35 Elizabeth St
Richmond
VIC
3121
Country
Australia
Secondary sponsor category [1] 311263 0
None
Name [1] 311263 0
Address [1] 311263 0
Country [1] 311263 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309856 0
The Gold Coast Hospital and Health District Human Research Ethics Committee
Ethics committee address [1] 309856 0
Ethics committee country [1] 309856 0
Australia
Date submitted for ethics approval [1] 309856 0
31/03/2022
Approval date [1] 309856 0
06/09/2022
Ethics approval number [1] 309856 0

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

Contacts
Principal investigator
Name 115626 0
A/Prof Tara Cochrane
Address 115626 0
Clinical and Laboratory Haematologist
Gold Coast University Hospital
1 Hospital Blvd, Southport QLD 4215
Country 115626 0
Australia
Phone 115626 0
+617 56872631
Fax 115626 0
Email 115626 0
[email protected]
Contact person for public queries
Name 115627 0
Delaine Smith
Address 115627 0
ALLG
Ground floor, 35 Elizabeth St
Richmond
VIC 3121
Country 115627 0
Australia
Phone 115627 0
+613 83739701
Fax 115627 0
Email 115627 0
[email protected]
Contact person for scientific queries
Name 115628 0
Delaine Smith
Address 115628 0
ALLG
Ground floor, 35 Elizabeth St
Richmond
VIC 3121
Country 115628 0
Australia
Phone 115628 0
+613 83739701
Fax 115628 0
Email 115628 0
[email protected]

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.