None listed
Conditions
Brief summary
This study aims to assess the effect of Tislelizumab (an immunological treatment) in combination with CHOP or mini-CHOP (chemotherapy regimes) for the treatment of elderly patients with early- or advanced-stage Hodgkin Lymphoma. Who is it for? You may be eligible for this study if you are aged 61 years or older and have a diagnosis of stage IIA to IVB Hodgkin Lymphoma. Study details Participants who choose to participate in this clinical trial will receive 3 cycles (each cycle is 3 weeks) of intravenous Tislelizumab given on day 1 of the cycle. Four-5 weeks later, treatment with Tislelizumab will continue for another 4-6 cycles (each cycle is 21 days) in combination with CHOP or mini-CHOP, which is a lower-dose version of CHOP that may be given to patients over the age of 80 or who would not tolerate the full dose CHOP. This will be followed by a further four 3-week cycles of Tislelizumab, or may be followed by radiotherapy at the discretion of the investigator. For participants who achieve a complete response, the total duration of therapy will be for 21 weeks for those with early-stage disease or 27 weeks for those with advanced stage disease. All participants will be followed-up for a minimum of 2 years after the end of treatment, which will continue until the last patient has completed their 2-year follow-up. PET-CT scans will be used to monitor the response to treatment throughout, and any side effects of treatment will be monitored through regular physical examinations, blood tests, and a questionnaire. It is hoped this research will determine whether Tislelizumab in combination with CHOP or mini-CHOP is effective and safe at treating Hodgkin Lymphoma in older patients, with tolerable toxicity.
Interventions
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 wh
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.
Sponsors
Australasian Leukaemia and Lymphoma Group
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
61 Years to No maximum
Healthy volunteers
No
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
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.
Outcome results
None listed