Professor Chan Cheah

Australasian Leukaemia & Lymphoma Group

ALLG NHL33

II

• Mantle Cell Lymphoma (MCL)

This trial is for patients <70 years of age with newly diagnosed mantle cell lymphoma who are otherwise in good health. Patients will begin the first part of treatment for two months which consists of rituximab and acalabrutinib. Rituximab is an antibody that is given as an intravenous infusion and targets the CD20 protein to trigger cell death. Acalabrutinib is a tablet taken by mouth twice daily and works by blocking a protein called BTK which leads to lymphoma cell death. Patients will also receive a standard chemotherapy program called R-DHAOx intravenously followed high dose chemotherapy and stem cell transplant. Patients will enter maintenance phase with acalabrutinib and rituximab.

Louise Hay

louise.hay@health.wa.gov.au

08 6383 3207

Inclusion:

1. Age 18 – 65 years
2. Histologically confirmed diagnosis of CD20 positive mantle cell lymphoma (MCL)
3. No prior lymphoma treatment including chemotherapy, radiotherapy or other investigational drug
4. Stage II-IV disease by Ann Arbor Criteria. Patients with stage I disease with bulk (greater than 7cms) that require systemic treatment will also be eligible. (must be able to undergo PET/CT imaging for staging purposes).
5. PET/CT avid disease at baseline.
6. Eastern Collaborative Oncology Group (ECOG) performance status 0, or 1, unless attributable to lymphoma in which case patients of performance status
7. are also eligible.
8. Adequate bone marrow function with haemoglobin greater than 80g/L, neutrophils greater than 1.0×109/L and platelets greater than 80×109/L at the time of study entry unless attributed to bone marrow infiltration by lymphoma.
9. Adequate renal function defined by an estimated creatinine clearance greater than or equal to 40 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
10. Adequate hepatic function defined by a total bilirubin level less than or equal to 2 × the upper limit of normal (ULN) range and AST and alanine aminotransferase (ALT) levels less than or equal to 3 × upper limit of institutional normal range unless attributed to lymphoma or Gilbert’s syndrome.
    10. Patients must have an acceptable left ventricular ejection fraction (LVEF) i.e. within the local normal range for gated heart pool scan or echocardiogram
11. Life expectancy greater than 3 months.
12. Negative blood pregnancy test at screening for women of childbearing potential.
13. Signed written informed consent before any trial-related procedure is undertaken that is not part of the standard patient management.

Exclusion:

1. Any lymphoma not fulfilling the WHO diagnostic criteria1 for mantle cell lymphoma
2. Central nervous system involvement including meningeal involvement or cord compression from lymphoma
3. Subjects aged less than 18 or more than 65 years at screening
4. Subjects that are deemed not suitable for autologous stem cell transplant, in the opinion of the treating physician, at time of screening.
5. Subjects with a contraindication to study treatments
6. Prior organ transplantation, including allogeneic stem-cell transplantation
7. Prior malignancy, active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
8. Major surgery for any reason, except diagnostic biopsy, within 4 weeks of enrolment and/or if the subject has not fully recovered from the surgery within 4 weeks of enrolment
9. Past history of interstitial lung disease.
10. Any other serious active disease
11. Presence of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS), Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening. Only patients who are HBV surface antigen (HBVsAg) and/or HBV core antibody (HBVcAb) positive are required to undergo HBV DNA PCR testing. Subjects that are HBV DNA negative who are HBVcAb positive are permitted in the study but must be on HBV prophylaxis.
12. Live vaccines within 30 days prior to the first dose of study drug and while participating in the study.

ACTRN12619000990123