An multi site clinical trial for patients with EBV associated Lymphomas - ALLG NHL36

Phase 1

• Conditions: ymphoma; Cancer - Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma; Lymphoma

• Registration Number: ACTRN12622001189718
• Lead Sponsor: Australasian Leukaemia and Lymphoma Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-09-06
• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

1. Local histological diagnosis (on core or excision biopsy) of de-novo systemic CD20+ EBV-associated DLBCL by EBER-ISH (positive is equals to or greater than 50% of lymphoma cells) without immunosuppression. (Immunosuppression includes lymphomas occurring after methotrexate, in patients with HIV, or following solid organ or haematopoietic stem cell transplant, and patients with inherited immunodeficiencies).
2. Stages II-IV (or I with bulk equal to or greater than 7.5cm or systemic ‘B’ symptoms).
3. Aged greater than 45 years
4. Adequate major organ function defined as
a.ANC (segs + bands) equal to or greater than 1.0 x 10^9/L (can be supported by G-CSF).
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 (Cockcroft-Gault formula)
f.LVEF within institutional normal limits (determined either by echocardiography or gated heart pool scan).
5. ECOG status 0-2 (2 if related to lymphoma)
6. Written informed consent.
7. Life expectancy at least 3 months
8. Men who are sexually active with women of child-bearing potential, and women of child-bearing potential, must use any highly effective contraceptive method during the study (failure rate greater then 1% per year) and for a period of 120 days after the last dose of therapy. Should pregnancy occur during therapy or before 120 days, the treating physician should be informed immediately.
9. PET/CT avid disease at baseline.
10. Positive EBV IgG serology.
11. Subjects must agree not to donate blood, semen or sperm while on study treatment and for least 120 days after treatment discontinuation
12. Subjects must agree not to share their medication and to return unused supplies
13. To take part in the PRO component of the study the subject must be able to read/write in English. Patients who do not meet this criteria can participate in the rest of the trial.

Exclusion Criteria

1. T cell lymphoma, transformed or 3B Follicular Lymphoma
2. CNS / meningeal / spinal cord involvement with lymphoma
3. Prior anti-PD-1 mAb
4. Active autoimmunity that might deteriorate when receiving an immunostimulatory agent. Note: Patients with the following diseases are not excluded and may proceed to further screening:
a.Controlled Type I diabetes
b.Hypothyroidism (provided it is managed with hormone replacement therapy only)
c.Controlled celiac disease
d.Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia)
e.Any other disease that is not expected to recur in the absence of external triggering factors
5. Chronic prednisolone is greater than 10mg (or equivalent). Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses is equal to 10 mg or 10 mg equivalent prednisone per day. Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable.
6. Uncontrolled systemic infection, including active Hepatitis B/C. Patients with Hep B core Ab positive and Hep B surface antigen negative are permitted in the trial only if they have negative HBV DNA and must be on HBV prophylaxis (choice of prophylaxis is at physician’s discretion, with local guidance). Patients who are Hep B surface antigen positive are NOT allowed. Prior treated Hep C is allowed, provided HCV RNA is not detected.
7. As there is ‘chemo-free’ induction, patients requiring urgent cyto-reductive therapy for life-threatening disease are excluded. Requirement for urgent treatment due to life-threatening complications include for example: Compressive symptoms due to disease (which may or may not be bulky), such as superior vena caval obstruction; significant organ involvement causing compromise of organ function (including but not limited to liver, renal obstruction), malignant, symptomatic hypercalcaemia
8. Anticipated to be unable to receive full-dose R-CHOP
9. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal, squamous cell skin cancer, low risk melanoma, superficial bladder cancer, localised cancer of the prostate cancer, cervix, or breast
10. Immunosuppression related lymphoma (e.g. PTLD, HIV, methotrexate).(Immunosuppression related lymphomas include those occurring after methotrexate, in patients with HIV, or following solid organ or haematopoietic stem cell transplant, and patients with inherited immunodeficiencies).
11. Previous treatment for current lymphoma (including chemotherapy, radiotherapy or investigational drug). Prior treatment for a histologically distinct lymphoma is permitted.
12. No concurrent uncontrolled medical condition as determined by investigator
13. Prior immune checkpoint blockade therapy
14. Use of pre-phase corticosteroids is discouraged (but permitted) due to the potential for reduction in Tislelizumab activity. However, if patients have received pre-phase steroids for symptom relief prior to screening they are not excluded.
15. Prior organ transplantation including allogeneic stem cell transplantation
16. Past history of interstitial lung disease (a rare side-effect of PD-1 blockade), non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.)
17. Known severe hype

Study & Design

• Study Type: Interventional
• Study Design: Not specified