Rituximab-CHOP Regimen - ENRICH Study

Transcription

1 Rituximab-CHOP Regimen - Study Randomised, open label study of Rituximab/Ibrutinib vs Rituximab/Chemotherapy in older patients with untreated mantle cell lymphoma ***See protocol for further details*** Available for Routine Use in Burton in-patient Derby in-patient Burton day-case Derby day-case Burton community Derby community Burton out-patient Derby out-patient Indication Untreated Mantle Cell Lymphoma Treatment Intent Palliative Anti-Emetics Pre-chemotherapy 2 Post-chemotherapy A Frequency & Every 21 days for up to 8 cycles Duration Single Dose Rituximab Day 1 Ondansetron 8mg As a single oral dose Paracetamol 1g As a single oral dose 30 minutes prior to rituximab Chlorphenamine 10mg As a single intravenous bolus Hydrocortisone 100mg As a single intravenous bolus Prednisolone 100mg Oral once daily for 5 daysgive first dose 30 minutes prior to rituximab Rituximab* 375mg/m 2 Intravenous infusion in 500ml sodium chloride 0.9% Cyclophosphamide 750mg/m 2 Intravenous bolus Doxorubicin 50mg/m 2 Intravenous bolus Vincristine 1.4mg/m 2 maximum 2mg (See notes) Intravenous infusion in 50ml sodium chloride 0.9% over 5-10 minutes Metoclopramide 10mg Oral four times daily for 2 days then as required AUTHORISED BY: Dr J Addada PAGE 1 of 8

2 Allopurinol 300mg Oral once daily for 1-2 cycles Co-trimoxazole 480mg Oral once daily for 21 days Omeprazole 20mg Oral once daily for 5 days Aciclovir 400mg Oral twice daily for 21 days * Rituximab may be given as a split dose, see below. Confirmed with Trial Sponsor, dated Split Dose Rituximab Day 1 Paracetamol 1g As a single oral dose 30 minutes prior to rituximab Chlorphenamine 10mg As a single intravenous bolus Hydrocortisone 100mg As a single intravenous bolus Prednisolone 100mg Oral once daily for 5 daysgive first dose 30 minutes prior to rituximab Rituximab 100mg Intravenous infusion in 100ml sodium chloride 0.9% over 4 hours Pethidine Ondansetron Cyclophosphamide 25mg 8mg 750mg/m 2 Intravenous bolus STAT if required for febrile infusion reaction As a single oral dose Intravenous bolus Doxorubicin 50mg/m 2 Intravenous bolus Vincristine 1.4mg/m 2 maximum 2mg (See notes) Intravenous infusion in 50ml sodium chloride 0.9% over 5-10 minutes Metoclopramide 10mg Oral four times daily for 2 days then as required Allopurinol 300mg Oral once daily for 1-2 cycles Co-trimoxazole 480mg Oral once daily for 21 days Omeprazole 20mg Oral once daily for 5 days Aciclovir 400mg Oral twice daily for 21 days Day 2 Paracetamol 1g As a single oral dose 30 minutes prior to rituximab AUTHORISED BY: Dr J Addada PAGE 2 of 8

3 Notes: Chlorphenamine 10mg As a single intravenous bolus Hydrocortisone 100mg As a single intravenous bolus Rituximab 375mg/m 2 minus 100mg (i.e. remainder of dose) Intravenous infusion in 500ml sodium chloride 0.9% using first infusion rate Pethidine 25mg Intravenous bolus STAT if required for febrile infusion reaction 1. Baseline Investigations Inclusion criteria: Absolute neutrophil count >1.0 x 10 9 /l or Platelets >100 x 10 9 /l independent of growth factor support or unless related to lymphoma Calculated creatinine clearance >30ml/min Hepatic function o Alanine aminotransferase (ALT) <3 x upper limit of normal (ULN) o Aspartate aminotransferase (AST) <3 x ULN o Total bilirubin 1.5 x ULN, unless bilirubin rise is due to Gilbert s syndrome or of non-hepatic origin 2. Randomisation should take place in enough time before cycle 1, day 1 to allow preparation time at the site pharmacy. 3. BSA will be capped at 2.2m 2. National dose banding tables can be used 4. Cardiac function sufficient to tolerate 300mg/m 2 of doxorubicin. A pretreatment echocardiogram is not mandated, but recommended in patients considered at higher risk of anthracycline cardiotoxicity. Cardiac assessment (e.g. MUGA) in those patients 65 years or those with a cardiac history. Rituximab This section should be read in conjunction with the Guidelines for the administration of Rituximab. AUTHORISED BY: Dr J Addada PAGE 3 of 8

4 1. The day 1 dose of prednisolone should be given 30 mins prior to receiving rituximab. Premedication consisting of analgesia and an antihistamine and an intravenous corticosteroid should always be administered 30 minutes before each infusion of rituximab. (e.g. paracetamol 1g oral STAT and chlorphenamine 4mg oral or 10mg IV bolus STAT and hydrocortisone 100mg IV STAT). In addition pethidine 25mg IV should be available in case of a severe infusion reaction. 2. Rituximab doses should be rounded to the nearest 100mg Use rituximab rate calculator to assist with rate escalation of rituximab infusion. 3. Occurrence of an Infusion Related Event or Hypersensitivity: Stop the infusion and contact a doctor. When symptoms improve, continue the infusion at half the rate prior to the reaction. Accelerate the infusion rate more slowly as tolerated by the patient. Dose modifications and toxicities Patients older than 70: consider reducing the initial vincristine dose to a fixed dose of 1mg ( elderly CHOP ) ), giving a 1 week steroid pre-phase and/or escalating the dose of anthracycline progressively with each cycle, e.g. 50% cycle 1, 75% cycle 2, 100% cycle 3, according to patient tolerability. 1. Haematological toxicity At the start of each cycle the neutrophil count should be > 1.0 x 10 9 /l and platelets > 100 x 10 9 /l AUTHORISED BY: Dr J Addada PAGE 4 of 8

5 a) Neutropenia b)thrombocytopenia AUTHORISED BY: Dr J Addada PAGE 5 of 8

6 2. Non-Haematological Toxicity 3. Renal impairment Cyclophosphamide GFR ml/min Dose % <10 50% Doxorubicin GFR ml/min Dose % < % Dose reduction for renal impairment is not required for vincristine or rituximab. 3. Hepatic impairment Cyclophosphamide Bilirubin Dose micromol/l <53 100% % Severe hepatic impairment may be associated with a decreased activation of cyclophosphamide. This may alter the effectiveness of the cyclophosphamide treatment. AUTHORISED BY: Dr J Addada PAGE 6 of 8

7 Doxorubicin Bilirubin micromol/l Dose <20 100% % >50 25% Vincristine Bilirubin micromol/l Dose % >51 50% Dose reduction for hepatic impairment is not required for rituximab. Supportive care 1. It is advisable to give allopurinol (300mg) once a day for the first 1 or 2 courses of therapy. Reduce dose to 100mg daily if GFR <10mls/min. 2. All patients should receive Pneumocystis jirovecii prophylaxis throughout treatment: Co-trimoxazole 480mg ONCE daily. In cases of allergy to cotrimoxazole, consider dapsone 100mg daily. Aciclovir 400mg twice daily. 3. Omeprazole 20mg once daily for 5 days (i.e. concurrently with prednisolone). 4. GCSF 300 micrograms once daily by subcutaneous injection on days 7, 9, 11 (& 13) if 65 years or has developed neutropenic sepsis with previous cycles of chemotherapy. References 1. Protocol versionv4, 19 th October Standard Care QACS Rituximab-CHOP, version 9, by C Ward, (CSIS regimen code R-CHOP). 3. Sandoz Ltd Summary of product characteristics for Cyclophosphamide, last updated 4 th December 2014 (accessed ). 4. Accord healthcare Ltd Summary of product characteristics for Doxorubicin, last updated 21 st January 2016 (accessed ). 5. Hospira UK Ltd Summary of product characteristics for Vincristine, last updated 18 th April 2016, (accessed ). AUTHORISED BY: Dr J Addada PAGE 7 of 8

8 6.Roche Products Ltd Summary of product characteristics for Rituximab, last updated 6 th June 2014 (accessed ). 7. The Renal Drug Database, AUTHORISED BY: Dr J Addada PAGE 8 of 8