THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST
Systemic Anti-Cancer Therapy Protocol
R-BAC
Relapsed/Refractory Non- Hodgkin’s Lymphoma
PROTOCOL REF: MPHARBACHA (Version No: 1.0)
Approved for use in: Relapsed or refractory Mantle Cell Lymphoma First line treatment of Mantle Cell Lymphoma in less fit patients unsuitable for more intensive treatment
Blueteq registration required (bendamustine)
Dosage:
Drug Dose Route Frequency Rituximab 375mg/m2 IV infusion Day 1 only Bendamustine 70mg/m2 IV infusion Days 2 and 3 (once daily) Cytarabine 500mg/m2 ** IV infusion Days 2 to 4 (once daily)
**Dose can be increased to 800mg/m2 if patient tolerates first cycle well – clinical decision.
Maximum of 6 cycles (cycle length 28 days)
Administration: Due to the long retention time of rituximab in B cell depleted patients, women of childbearing potential must employ effective contraceptive methods during and for 12 months after treatment with rituximab. Patients will required irradiated blood products (lifelong) –the patients receive information booklets about irradiated blood when counselled by the specialist nurses. It
Issue Date: 11th December 2020 Page 1 of 6 Protocol reference: MPHARBACHA Review Date: December 2023 Author: Aileen McCaughey Authorised by: DTC Version No: 1.0
THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST
contains an alert card that the patient carries around with them. The specialist nurses then contact the lab.
Anti-emetic risk: Severely emetogenic.
Supportive treatments: Rituximab pre-infusion medicines: Paracetamol PO 1g Chlorphenamine IV bolus 10mg Hydrocortisone IV bolus 100mg
Bendamustine/Cytarabine pre-infusion medicines: Ondansetron PO 8mg
Supportive medicines: Allopurinol PO 100mg or 300mg daily (depending on renal function) for first cycle Ondansetron PO 8mg twice daily days 2-6 treatment Metoclopramide PO 10mg three times a day when required Chlorhexidine 0.2% mouthwash 10mls four times a day Co-trimoxazole 480mg daily Corticosteroid eye drops 1 drop to both eyes four times a days 2-7 Consider filgrastim S/C 300 or 480 micrograms OD from day 7 for 7 days (300 micrograms if <70kg and 480 micrograms ≥70kg) Consider Aciclovir 400mg twice daily if history of shingles
Extravasation risk: Rituximab: non-vesicant Bendamustine: vesicant Cytarabine: non-vesicant
Refer to the Trust guidance for the prevention and management of extravasation
Issue Date: 11th December 2020 Page 2 of 6 Protocol reference: MPHARBACHA Review Date: December 2023 Author: Aileen McCaughey Authorised by: DTC Version No: 1.0
THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST
Interactions: Rituximab No significant interactions
Bendamustine Bendamustine metabolism involves cytochrome P450 (CYP) 1A2 isoenzyme. Therefore, the potential for interaction with CYP1A2 inhibitors such as fluvoxamine, ciprofloxacin, aciclovir and cimetidine exists.
Cytarabine Cytarabine may reduce digoxin levels. Digoxin level monitoring is recommended. An in-vitro interaction study between gentamicin and cytarabine showed a cytarabine related antagonism for the susceptibility of K. pneumoniae strains. In patients on cytarabine being treated with gentamicin for a K.pneumoniae infection, a lack of a prompt therapeutic response may indicate the need for re-evaluation of antibacterial therapy.
Treatment schedule: Day Drug Dose Route Diluent and rate 1 Hydrocortisone sodium 100mg IV bolus 30 mins before chemotherapy succinate Paracetamol 1g PO 30 mins before chemotherapy Chlorphenamine 10mg IV bolus 30 mins before chemotherapy In 500mls sodium chloride IV Rituximab 375mg/m2 0.9%. For infusion time see infusion rituximab infusion rate policy. 2 Ondansetron 8mg PO IV In 500mls sodium chloride Bendamustine 70mg/m2 infusion 0.9% over 1 hour In 500mls sodium chloride 0.9% over 2 hours. IV Cytarabine 500mg/m2** NB Cytarabine must start 2 infusion hours after completion of bendamustine. 3 Ondansetron 8mg PO IV In 500mls sodium chloride Bendamustine 70mg/m2 infusion 0.9% over 1 hour
Issue Date: 11th December 2020 Page 3 of 6 Protocol reference: MPHARBACHA Review Date: December 2023 Author: Aileen McCaughey Authorised by: DTC Version No: 1.0
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In 500mls sodium chloride 0.9% over 2 hours. IV Cytarabine 500mg/m2** NB Cytarabine must start 2 infusion hours after completion of bendamustine. Ondansetron 8mg PO In 500mls sodium chloride 0.9% over 2 hours. 4 IV Cytarabine 500mg/m2** NB Cytarabine must start 2 infusion hours after completion of bendamustine.
** Consider increasing dose to 800mg/m2 if patient tolerates first cycle well
Main toxicities: Thrombocytopenia, neutropenia, anaemia, nausea, vomiting, diarrhoea, conjunctivitis, infusion related reactions, cytokine release syndrome, reactivation of hepatitis B and Steven- Johnson syndrome.
Issue Date: 11th December 2020 Page 4 of 6 Protocol reference: MPHARBACHA Review Date: December 2023 Author: Aileen McCaughey Authorised by: DTC Version No: 1.0
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Investigations and treatment plan:
Cycle 1+ Cycle 1+ Cycle 1+ Pre Ongoing Day 1 Day 2 Day 3 Informed consent x
Clinical Assessment x x As clinically indicated or at the end of treatment
SACT Assessment (including toxicity Every cycle assessment and informed x x x consent) FBC x x Every cycle U&E & LFTs & Magnesium x x Every Cycle CrCl (Cockcroft and Gault) x Every cycle Hepatitis B core antibody and surface antigens & Hep x C & HIV 1+2 PET CT Scan x Repeat at end of treatment CT Scan Interim scan after 3 cycles ECG If clinically indicated Blood pressure Continuous monitoring required while on rituximab measurement x x Temperature and Continuous monitoring required while on rituximab Respiratory Rate x Weight recorded x x Every cycle Pregnancy test x If clinically appropriate
Issue Date: 11th December 2020 Page 5 of 6 Protocol reference: MPHARBACHA Review Date: December 2023 Author: Aileen McCaughey Authorised by: DTC Version No: 1.0
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Dose Modifications and Toxicity Management: Haematological toxicity: Proceed on day 1 if- ANC ≥ 1.0 x 109/L Plt ≥ or 100 x109/L
Delay for one week if cytopenias not disease related. Consider dose reductions, discuss with consultant.
Dosing in renal and hepatic impairment: Bendamustine Hepatic Bilirubin (micromole/L) Dose adjustment 20-50 70% of dose >51 Not recommended Renal CrCl (ml/min) Advice <10 Caution required
References: 1. https://www.medicines.org.uk/emc rituximab (accessed July 2020) 2. https://www.medicines.org.uk/emc bendamustine (accessed July 2020) 3. https://www.medicines.org.uk/emc cytarabine (accessed July 2020) 4. Krens S D, Lassche, Jansman G F G A, et al. Dose recommendations for anticancer drugs in patients with renal or hepatic impairment. Lancet Oncol 2019; 20: e201–08. 5. Lancashire and South Cumbria Cancer Network. R-BAC-800 chemotherapy regime. Thames Valley Strategic Clinical Network. RBAC protocol. Accessed Nov 2020.
Issue Date: 11th December 2020 Page 6 of 6 Protocol reference: MPHARBACHA Review Date: December 2023 Author: Aileen McCaughey Authorised by: DTC Version No: 1.0