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Systemic Anti-Cancer Therapy Regimen Library

Home > LEU ALL precursor B-cell - HyperCVAD with RITUximab Part A and B followed by POMP Maintenance [60 years and under] > LEU - HyperCVAD with RITUximab [60 years and under] Part A with Intrathecal CNS prophylaxis Unknown Risk [default]
This regimen is a component of LEU ALL precursor B-cell - HyperCVAD with RITUximab Part A and B followed by POMP Maintenance [60 years and under]

HyperCVAD with RITUximab [60 years and under] - Part A with CNS prophylaxis for Unknown Risk [default] (LEU ALL precursor B-cell - HyperCVAD with RITUximab Part A and B followed by POMP Maintenance [60 years and under])

Treatment Overview

Alternates with a cycle of Part B every 21 days, or sooner if counts have recovered.

Intrathecal therapy included in this regimen is for CNS prophylaxis for patients with Unknown Risk [default].


For patients under 40 years of age, if not in morphological remission after Cycle 1A consider switching to regimen with pegaspargase as follows: 

LEU ALL precursor B-cell – HyperCVAD with RITUximab and pegaspargase Part A and B followed by POMP Maintenance [under 40 years] commencing cycle 1B.


This regimen contains a medicine where one or more biosimilars may exist. Any biosimilars used have been reviewed by the regulator (Medsafe) and relevant specialists were consulted nationally. Where regulators, in consultation with relevant specialists, have agreed that there are no clinically significant differences in either safety or effectiveness between a biosimilar and originator product, these drugs may be used interchangeably.

Cycles 1 to 2 - 21 days

Cycle length:
21

RITUximab, first dose:

  • Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.
  • For patients at high risk of infusion-related reaction, consider additional pre-medications such as an extra antihistamine dose the day before, an H2 receptor antagonist and montelukast.

Intrathecal metHOTREXATe: For Ommaya reservoir reduce dose to 6 mg intraventricularly.


DOXOrubicin: Some centres may choose to administer DOXOrubicin over 15 minutes.


filgrastim: Give filgrastim 5 micrograms/kg subcutaneously ONCE daily from Day 5 until neutrophil recovery past the nadir.

Cycles 3 to 4 - 21 days

Cycle length:
21

DOXOrubicin: Some centres may choose to administer DOXOrubicin over 15 minutes.


filgrastim: Give filgrastim 5 micrograms/kg subcutaneously ONCE daily from Day 5 until neutrophil recovery past the nadir.

Cycle details

Cycles 1 to 2 - 21 days

Medication Dose Route Days Max Duration
dexamethasone 40 mg flat dosing Once daily oral administration 1 to 4,
11 to 14
paracetamol * 1000 mg flat dosing oral administration 1, 11
loratadine * 10 mg oral administration 1, 11
RITUximab * 375 mg/m² intravenous 1, 11 6 hours
mesna * 600 mg/m² Once daily intravenous 1, 2, 3 24 hours
CYCLOPHOSPHamide 300 mg/m² Twice daily intravenous 1, 2, 3 3 hours
metHOTREXATe 12 mg flat dosing intrathecal injection 2
DOXOrubicin * 50 mg/m² intravenous 4 24 hours Min: 24 hours
vinCRISTine 2 mg flat dosing intravenous 4, 11 10 minutes
filgrastim 5 microgram/kg Once daily subcutaneous injection 5
cytarabine 100 mg flat dosing intrathecal injection 8

RITUximab, first dose:

  • Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.
  • For patients at high risk of infusion-related reaction, consider additional pre-medications such as an extra antihistamine dose the day before, an H2 receptor antagonist and montelukast.

Intrathecal metHOTREXATe: For Ommaya reservoir reduce dose to 6 mg intraventricularly.


DOXOrubicin: Some centres may choose to administer DOXOrubicin over 15 minutes.


filgrastim: Give filgrastim 5 micrograms/kg subcutaneously ONCE daily from Day 5 until neutrophil recovery past the nadir.

Cycles 3 to 4 - 21 days

Medication Dose Route Days Max Duration
dexamethasone 40 mg flat dosing Once daily oral administration 1 to 4,
11 to 14
mesna * 600 mg/m² Once daily intravenous 1, 2, 3 24 hours
CYCLOPHOSPHamide 300 mg/m² Twice daily intravenous 1, 2, 3 3 hours
DOXOrubicin * 50 mg/m² intravenous 4 24 hours Min: 24 hours
vinCRISTine 2 mg flat dosing intravenous 4, 11 10 minutes
filgrastim 5 microgram/kg Once daily subcutaneous injection 5

DOXOrubicin: Some centres may choose to administer DOXOrubicin over 15 minutes.


filgrastim: Give filgrastim 5 micrograms/kg subcutaneously ONCE daily from Day 5 until neutrophil recovery past the nadir.

Full details

Cycles 1 to 2 - 21 days

Day: 1

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food, at least 30 to 60 minutes prior to RITUximab.
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab * 375 mg/m² intravenous 6 hours
Instructions:

First administration:

  • Consider withholding routine anti-hypertensives for 12 hours prior to first RITUximab dose.
  • For patients at high risk of infusion-related reaction, consider additional pre-medications such as an extra antihistamine dose the day before, an H2 receptor antagonist and montelukast.
  • Start infusion at 50 mg/hour. If tolerated, rate can be increased by 50 mg/hour every 30 minutes to a maximum rate of 400 mg/hour.
mesna * 600 mg/m² Once daily intravenous 24 hours
Instructions:

Continuous infusion over 24 hours.

  • Commence ONE hour before the first dose of CYCLOPHOSPHamide and stop 12 hours after completion of the last dose of CYCLOPHOSPHamide.
CYCLOPHOSPHamide 300 mg/m² Twice daily intravenous 3 hours
Instructions:

Every 12 hours.

  • Consider hydration with at least 2000 ml over 24 hours as oral or IV fluid on day(s) of CYCLOPHOSPHamide and for 24 hours after or as per institutional practice.

Day: 2

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.
mesna * 600 mg/m² Once daily intravenous 24 hours
Instructions:

Continuous infusion over 24 hours.

  • Commence ONE hour before the first dose of CYCLOPHOSPHamide and stop 12 hours after completion of the last dose of CYCLOPHOSPHamide.
CYCLOPHOSPHamide 300 mg/m² Twice daily intravenous 3 hours
Instructions:

Every 12 hours.

  • Consider hydration with at least 2000 ml over 24 hours as oral or IV fluid on day(s) of CYCLOPHOSPHamide and for 24 hours after or as per institutional practice.
metHOTREXATe 12 mg flat dosing intrathecal injection
Instructions:
  • Adhere to local institution policy for intrathecal administration.
  • For Ommaya reservoir reduce dose to 6 mg intraventricularly.

Day: 3

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.
mesna * 600 mg/m² Once daily intravenous 24 hours
Instructions:

Continuous infusion over 24 hours.

  • Commence ONE hour before the first dose of CYCLOPHOSPHamide and stop 12 hours after completion of the last dose of CYCLOPHOSPHamide.
CYCLOPHOSPHamide 300 mg/m² Twice daily intravenous 3 hours
Instructions:

Every 12 hours.

  • Consider hydration with at least 2000 ml over 24 hours as oral or IV fluid on day(s) of CYCLOPHOSPHamide and for 24 hours after or as per institutional practice.

Day: 4

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.
DOXOrubicin * 50 mg/m² intravenous 24 hours Min: 24 hours
Instructions:

Continuous infusion over 24 hours.

  • Some centres may choose to administer over 15 minutes.
  • Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
vinCRISTine 2 mg flat dosing intravenous 10 minutes
Instructions:
  • Diluted in a minibag.
  • FOR INTRAVENOUS USE ONLY - fatal if given by any other routes.
  • Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.

Day: 5

Medication Dose Route Max duration Details
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:

Give ONCE daily from Day 5 until neutrophil recovery past the nadir.

  • Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Day: 8

Medication Dose Route Max duration Details
cytarabine 100 mg flat dosing intrathecal injection
Instructions:

Adhere to local institution policy for intrathecal administration.

Day: 11

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food, at least 30 to 60 minutes prior to RITUximab.
paracetamol * 1000 mg flat dosing oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
loratadine * 10 mg oral administration
Instructions:

30 to 60 minutes prior to RITUximab.
RITUximab * 375 mg/m² intravenous 6 hours
Instructions:

Start infusion at 100 mg/hour. If tolerated, rate can be increased by 100 mg/hour every 30 minutes to a maximum rate of 400 mg/hour, or as per institutional practice.
vinCRISTine 2 mg flat dosing intravenous 10 minutes
Instructions:
  • Diluted in a minibag.
  • FOR INTRAVENOUS USE ONLY - fatal if given by any other routes.
  • Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.

Day: 12

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.

Day: 13

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.

Day: 14

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.

Cycles 3 to 4 - 21 days

Day: 1

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.
mesna * 600 mg/m² Once daily intravenous 24 hours
Instructions:

Continuous infusion over 24 hours.

  • Commence ONE hour before the first dose of CYCLOPHOSPHamide and stop 12 hours after completion of the last dose of CYCLOPHOSPHamide.
CYCLOPHOSPHamide 300 mg/m² Twice daily intravenous 3 hours
Instructions:

Every 12 hours.

  • Consider hydration with at least 2000 ml over 24 hours as oral or IV fluid on day(s) of CYCLOPHOSPHamide and for 24 hours after or as per institutional practice.

Day: 2

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.
mesna * 600 mg/m² Once daily intravenous 24 hours
Instructions:

Continuous infusion over 24 hours.

  • Commence ONE hour before the first dose of CYCLOPHOSPHamide and stop 12 hours after completion of the last dose of CYCLOPHOSPHamide.
CYCLOPHOSPHamide 300 mg/m² Twice daily intravenous 3 hours
Instructions:

Every 12 hours.

  • Consider hydration with at least 2000 ml over 24 hours as oral or IV fluid on day(s) of CYCLOPHOSPHamide and for 24 hours after or as per institutional practice.

Day: 3

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.
mesna * 600 mg/m² Once daily intravenous 24 hours
Instructions:

Continuous infusion over 24 hours.

  • Commence ONE hour before the first dose of CYCLOPHOSPHamide and stop 12 hours after completion of the last dose of CYCLOPHOSPHamide.
CYCLOPHOSPHamide 300 mg/m² Twice daily intravenous 3 hours
Instructions:

Every 12 hours.

  • Consider hydration with at least 2000 ml over 24 hours as oral or IV fluid on day(s) of CYCLOPHOSPHamide and for 24 hours after or as per institutional practice.

Day: 4

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.
DOXOrubicin * 50 mg/m² intravenous 24 hours Min: 24 hours
Instructions:

Continuous infusion over 24 hours.

  • Some centres may choose to administer over 15 minutes.
  • Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.
vinCRISTine 2 mg flat dosing intravenous 10 minutes
Instructions:
  • Diluted in a minibag.
  • FOR INTRAVENOUS USE ONLY - fatal if given by any other routes.
  • Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.

Day: 5

Medication Dose Route Max duration Details
filgrastim 5 microgram/kg Once daily subcutaneous injection
Instructions:

Give ONCE daily from Day 5 until neutrophil recovery past the nadir.

  • Round dose to nearest prefilled syringe dose of 300 micrograms or 480 micrograms.

Day: 11

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.
vinCRISTine 2 mg flat dosing intravenous 10 minutes
Instructions:
  • Diluted in a minibag.
  • FOR INTRAVENOUS USE ONLY - fatal if given by any other routes.
  • Warning vesicant—ensure vein is patent prior to administration, administer vesicant as per institutional policy and monitor for signs of extravasation throughout administration.

Day: 12

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.

Day: 13

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.

Day: 14

Medication Dose Route Max duration Details
dexamethasone 40 mg flat dosing Once daily oral administration
Instructions:

Take in the morning with food.

Supportive Care Factors

Factor Value
Antifungal prophylaxis: Routine antifungal prophylaxis recommended
Antiviral prophylaxis for hepatitis B virus: Required for anti–HBc positive patients at risk of reactivation
Antiviral prophylaxis for herpes virus: Routine antiviral prophylaxis recommended
Constipation risk: Consider prescribing laxatives with this treatment
Emetogenicity: Variable
Gastroprotection: Gastroprotection is recommended
Growth factor support: Recommended for primary prophylaxis
Hypersensitivity / Infusion related reaction risk: Variable
Mesna uroprotection: Routine mesna uroprotection recommended
Pneumocystis jirovecii pneumonia (PJP) prophylaxis: Routine antibiotic prophylaxis recommended
Tumour lysis syndrome prophylaxis: Variable

Antifungal prophylaxis: Inhibition of CYP3A4 by azole antifungals may lead to reduced vinCRISTine clearance and increased toxicities. Strategies to avoid this interaction may include a washout period after azole administration or using a non-azole antifungal for prophylaxis.


Emetogenicity: MEDIUM days 1 to 4; MINIMAL day 11.


Gastroprotection: Gastroprotection agents are only intended for short term use while patient is receiving corticosteroid treatment doses.


Hypersensitivity/Infusion related reaction risk: HIGH - routine premedication recommended for RITUximab containing cycles.


Tumour lysis syndrome prophylaxis: Recommended for first cycle (1A) and only for further cycles if not in complete remission.

References

Tabernero J, Vyas M, Giuliani R, Arnold D, Cardoso F, Casali PG, Cervantes A, Eggermont AMM, Eniu A, Jassem J, Pentheroudakis G, Peters S, Rauh S, Zielinski CC, Stahel RA, Voest E, Douillard JY, McGregor K, Ciardiello F. Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers. ESMO Open. 2017 Jan 16;1(6):e000142. doi: 10.1136/esmoopen-2016-000142., PMID: 28848668

Lyman GH, Balaban E, Diaz M, Ferris A, Tsao A, Voest E, Zon R, Francisco M, Green S, Sherwood S, Harvey RD, Schilsky RL. American Society of Clinical Oncology Statement: Biosimilars in Oncology. J Clin Oncol. 2018 Apr 20;36(12):1260-1265. doi: 10.1200/JCO.2017.77.4893. Epub 2018 Feb 14., PMID: 29443651

Doyle J, Raggatt M, Slavin M, McLachlan SA, Strasser SI, Sasadeusz JJ, Howell J, Hajkowicz K, Nandurkar H, Johnston A, Bak N, Thompson AJ. Hepatitis B management during immunosuppression for haematological and solid organ malignancies: an Australian consensus statement. Med J Aust. 2019 Jun;210(10):462-468. doi: 10.5694/mja2.50160. Epub 2019 May 19. , PMID: 31104328

Medicines and Hepatitis B Reactivation Prescriber Update 38(1): 2-3 March 2017 https://medsafe.govt.nz/profs/PUArticles/March2017/MedicinesAndHepatitisB.htm.

Rituximab and Hepatitis B Reactivation Prescriber Update 34(3):27 September 2013 https://www.medsafe.govt.nz/profs/PUArticles/Sept2013RituximabHepB.htm.

* The medicines, doses, combinations, and schedule in this treatment regimen have been carefully reviewed against international best practice guidelines by specialists in medical oncology around New Zealand and this advice has been accepted for publication by Te Aho o Te Kahu (the Cancer Control Agency). Sometimes medicines that are used in routine clinical practice have not been through a formal review process by the NZ Medicines Regulator Medsafe and are therefore considered unapproved or off-label. These medicines are legally able to be prescribed through sections 25 and 29 of the Medicines Act and by obtaining informed consent from patients. All treatment regimens listed on this website have been through robust peer review and are considered an accepted standard of care, whether prescribed through sections 25 or 29 or carrying formal Medsafe Approval.

s29: This symbol indicates that some formulations of the associated medicine are legally only able to be prescribed under section 29 of the Medicines Act. You can see which formulations are section 29 by hovering over the s29 symbol. You can access full medication details from the New Zealand Formulary by clicking on the medication name. Each clinician retains full responsibility for ensuring they have complied with all relevant obligations and requirements of section 29 including obtaining informed patient consent prior to prescribing the applicable medicine.