None listed
Conditions
Brief summary
This purpose of this study to evaluate the efficacy and safety of Acalabrutinib and Rituximab followed by R-DHAOx chemo with or without ASCT and maintenance Aacalabrutinib and Rituximab in fit patients with previously untreated mantle cell lymphoma. Who is it for? You may be eligible for this study if you are an adult who has been diagnosed with positive mantle cell lymphoma. Study details All participants in this study will receive the following: 1. Induction phase: one day of Rituximab in the vein and 28 days Acalabrutinib orally for 2 cycles. 2. Chemotherapy phase: 4 cycles of chemotherapy (21 day cycles) 3. Consolidation phase: including stem cell transplant 4. Maintenance phase: Acalabrutinib orally for one year and Rituximab in the vein every 3 months for 2 years. During the trial patients will have blood tests performed and undergo up to 5 PET/CT scans to help determined the progress of the treatment. It is hoped that this research will help determine whether this treatment is safe for patients, and what kinds of side effects/complications may occur with this treatment.
Interventions
All patients will receive:
Induction phase: (Acalabrutinib + Rituximab 2 cycles every 4 weeks, cycle = 28 days)
Rituximab 375mg/m2 Intravenously D1
Acalabrutinib 100mg orally, twice a day, D1-D28
Followed by:
Chemotherapy phase: R-DHAOx 4 cycles every 21 days
Rituximab 375 mg/m2 Intravenously on day 1
Dexamethasone 40 mg Intravenously or Orally (tablets) on days 1 to 4 (the mode of administration is based on local site practice and availability)
Cytarabine 2000 mg/m2 Intravenously every 12 h o
All patients will receive: Induction phase: (Acalabrutinib + Rituximab 2 cycles every 4 weeks, cycle = 28 days) Rituximab 375mg/m2 Intravenously D1 Acalabrutinib 100mg orally, twice a day, D1-D28 Followed by: Chemotherapy phase: R-DHAOx 4 cycles every 21 days Rituximab 375 mg/m2 Intravenously on day 1 Dexamethasone 40 mg Intravenously or Orally (tablets) on days 1 to 4 (the mode of administration is based on local site practice and availability) Cytarabine 2000 mg/m2 Intravenously every 12 h on day 2 Oxaliplatin 100 mg/m² Intravenously on day 1. IF response to R-DHAOx is less than a partial response the patient will be taken off study and treated as per local guidelines. The response will be determined by review of a PET/CT scan taken after the patient has completed 4 cycles of R-DHAOx. IF response to R-DHAOx is greater than or equal to a partial response proceed to: Consolidation phase: BEAM Autologous stem cell transplant Carmustine 300 mg/m2 Intravenously on day -6 Etoposide 200 mg/m2 Intravenously on days -5 to -2 Cytarabine 200mg/m2 Intravenously TWICE a day on days -5 to -2 Melphalan 140 mg/m2 Intravenously on day -1 Peripheral stem cells injected on day 0 - dose to be determined on day by physician. Followed by: Maintenance phase: All patients with a documented response at end of the chemotherapy phase will continue with 1-year of Acalabrutinib 100mg orally, twice a day continuous, and 2 years of Rituximab 375mg/m2 Intravenously every 3 months for 8 doses Patients will be given patient diaries to monitor adherence to treatment.
Sponsors
Australasian Leukaemia and Lymphoma Group
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 – 70 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 2 are also eligible. 7. Adequate bone marrow function with haemoglobin greater than 80g/L, neutrophils greater than 1.0x109/L and platelets greater than 80x109/L at the time of study entry unless attributed to bone marrow infiltration by lymphoma. 8. 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). 9. 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 criteria
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 70 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. 13. Uncontrolled AIHA (autoimmune hemolytic anaemia) or ITP (idiopathic thrombocytopenia pupura). 14. Suspicion of or confirmed progressive multifocal leukoencephalopathy 15. Has difficulty with or is unable to swallow oral medication, or significant gastrointestinal disease that would limit absorption of oral medication 16. Pregnant or lactating
Outcome results
None listed