Systemic Anti-Cancer Therapy Regimen Library
UKALL14 with RITUximab [over 40 years] [for transplant] - Intensification/CNS prophylaxis (LEU ALL precursor B-cell - UKALL14 with RITUximab [over 40 years] [for transplant])
Treatment Overview
Starts after count recovery from Phase 2 Induction, with neutrophils greater than 0.75 x 109/L and platelets greater than 75 x 109/L.
High dose metHOTREXATe
- metHOTREXATe levels MUST be measured once every 24 hours.
- Intravenous alkalinized fluids MUST be commenced at least 6 hours before the start of metHOTREXATe infusion and MUST continue until the metHOTREXATe serum level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice). Additional oral alkalinization can be considered as Ural® 2 sachets orally the night before and 2 sachets the morning of high dose metHOTREXATe infusion.
- Before commencing the high dose metHOTREXATe infusion, urinary pH MUST be 7.5 or above (pH 7.5 to 8.0).
- Closely monitor renal function, electrolytes, fluid balance, and weight.
- foliNIc acid MUST start 36 hours after start of metHOTREXATe infusion and MUST continue to be administered until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
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.
Cycle 1 - 28 days
foliNIc acid: MUST start 36 hours after start of metHOTREXATe infusion and MUST continue to be administered until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
pegaspargase:
- DO NOT use in BCR-ABL1+ (Philadelphia positive) patients.
- There is limited data available for use of pegaspargase in patients 65 years and older. Strongly consider not using pegaspargase in patients 65 years and older.
- Consideration can be given to reducing dose of pegaspargase to 500 international units/m2 for certain patients.
- Monitor patients for one hour after administration of pegaspargase in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (e.g. adrenaline, oxygen, intravenous steroids, antihistamines).
- See also Additional details for Further information on pegaspargase.
RITUximab: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Cycle details
Cycle 1 - 28 days
Medication | Dose | Route | Days | Max Duration |
---|---|---|---|---|
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% | 125 mL/m²/hour | intravenous | 1 to 4, 15 to 18 |
|
sodium bicarbonate | 50 mmol | intravenous | 1 to 4, 15 to 18 |
|
acetazolamide * | 250 mg Four times daily | oral administration | 1 to 4, 15 to 18 |
|
metHOTREXATe | 300 mg/m² | intravenous | 1, 15 | 60 minutes |
metHOTREXATe | 2700 mg/m² | intravenous | 1, 15 | 23 hours |
foliNIc acid (as calcium folinate) | 30 mg flat dosing Every three hours | intravenous | 2, 3, 16, 17 |
2 minutes |
foliNIc acid (as calcium folinate) | 30 mg flat dosing Every six hours | intravenous | 3, 4, 17, 18 |
2 minutes |
paracetamol * | 1000 mg flat dosing | oral administration | 2, 3, 16, 17 |
|
loratadine * | 10 mg | oral administration | 2, 3, 16, 17 |
|
famotidine * | 20 mg | oral administration | 2, 16 | |
pegaspargase * | 1000 international unit/m² | intravenous | 2, 16 | 120 minutes |
RITUximab * | 375 mg/m² | intravenous | 3, 17 | 6 hours |
foliNIc acid: MUST start 36 hours after start of metHOTREXATe infusion and MUST continue to be administered until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1 µmol/L (level as per institutional practice).
pegaspargase:
- DO NOT use in BCR-ABL1+ (Philadelphia positive) patients.
- There is limited data available for use of pegaspargase in patients 65 years and older. Strongly consider not using pegaspargase in patients 65 years and older.
- Consideration can be given to reducing dose of pegaspargase to 500 international units/m2 for certain patients.
- Monitor patients for one hour after administration of pegaspargase in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (e.g. adrenaline, oxygen, intravenous steroids, antihistamines).
- See also Additional details for Further information on pegaspargase.
RITUximab: Consider administering corticosteroid premedication prior to RITUximab if previous doses not well tolerated or if clinically indicated as per institutional practice.
Full details
Cycle 1 - 28 days
Day: 1
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% | 125 mL/m²/hour | intravenous |
Instructions:
|
|
sodium bicarbonate | 50 mmol | intravenous |
Instructions:
|
|
acetazolamide * | 250 mg Four times daily | oral administration |
Instructions:
When required.
|
|
metHOTREXATe | 300 mg/m² | intravenous | 60 minutes | |
metHOTREXATe | 2700 mg/m² | intravenous | 23 hours |
Instructions:
Continuous infusion over 23 hours starting immediately after the 60 minute metHOTREXATe infusion. |
Day: 2
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% | 125 mL/m²/hour | intravenous |
Instructions:
|
|
sodium bicarbonate | 50 mmol | intravenous |
Instructions:
|
|
acetazolamide * | 250 mg Four times daily | oral administration |
Instructions:
When required.
|
|
foliNIc acid (as calcium folinate) | 30 mg flat dosing Every three hours | intravenous | 2 minutes |
Instructions:
|
paracetamol * | 1000 mg flat dosing | oral administration |
Instructions:
30 minutes prior to pegaspargase. |
|
loratadine * | 10 mg | oral administration |
Instructions:
30 minutes prior to pegaspargase. |
|
famotidine * | 20 mg | oral administration |
Instructions:
30 minutes prior to pegaspargase. |
|
pegaspargase * | 1000 international unit/m² | intravenous | 120 minutes |
Instructions:
Additional details:
|
Day: 3
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% | 125 mL/m²/hour | intravenous |
Instructions:
|
|
sodium bicarbonate | 50 mmol | intravenous |
Instructions:
|
|
acetazolamide * | 250 mg Four times daily | oral administration |
Instructions:
When required.
|
|
foliNIc acid (as calcium folinate) | 30 mg flat dosing Every three hours | intravenous | 2 minutes |
Instructions:
|
foliNIc acid (as calcium folinate) | 30 mg flat dosing Every six hours | intravenous | 2 minutes |
Instructions:
|
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:
|
Day: 4
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% | 125 mL/m²/hour | intravenous |
Instructions:
|
|
sodium bicarbonate | 50 mmol | intravenous |
Instructions:
|
|
acetazolamide * | 250 mg Four times daily | oral administration |
Instructions:
When required.
|
|
foliNIc acid (as calcium folinate) | 30 mg flat dosing Every six hours | intravenous | 2 minutes |
Instructions:
|
Day: 15
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% | 125 mL/m²/hour | intravenous |
Instructions:
|
|
sodium bicarbonate | 50 mmol | intravenous |
Instructions:
|
|
acetazolamide * | 250 mg Four times daily | oral administration |
Instructions:
When required.
|
|
metHOTREXATe | 300 mg/m² | intravenous | 60 minutes | |
metHOTREXATe | 2700 mg/m² | intravenous | 23 hours |
Instructions:
Continuous infusion over 23 hours starting immediately after the 60 minute metHOTREXATe infusion. |
Day: 16
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% | 125 mL/m²/hour | intravenous |
Instructions:
|
|
sodium bicarbonate | 50 mmol | intravenous |
Instructions:
|
|
acetazolamide * | 250 mg Four times daily | oral administration |
Instructions:
When required.
|
|
foliNIc acid (as calcium folinate) | 30 mg flat dosing Every three hours | intravenous | 2 minutes |
Instructions:
|
paracetamol * | 1000 mg flat dosing | oral administration |
Instructions:
30 minutes prior to pegaspargase. |
|
loratadine * | 10 mg | oral administration |
Instructions:
30 minutes prior to pegaspargase. |
|
famotidine * | 20 mg | oral administration |
Instructions:
30 minutes prior to pegaspargase. |
|
pegaspargase * | 1000 international unit/m² | intravenous | 120 minutes |
Instructions:
Additional details:
|
Day: 17
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% | 125 mL/m²/hour | intravenous |
Instructions:
|
|
sodium bicarbonate | 50 mmol | intravenous |
Instructions:
|
|
acetazolamide * | 250 mg Four times daily | oral administration |
Instructions:
When required.
|
|
foliNIc acid (as calcium folinate) | 30 mg flat dosing Every three hours | intravenous | 2 minutes |
Instructions:
|
foliNIc acid (as calcium folinate) | 30 mg flat dosing Every six hours | intravenous | 2 minutes |
Instructions:
|
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:
|
Day: 18
Medication | Dose | Route | Max duration | Details |
---|---|---|---|---|
potassium chloride 20mmol/1000mL + sodium chloride 0.18% + glucose 4% | 125 mL/m²/hour | intravenous |
Instructions:
|
|
sodium bicarbonate | 50 mmol | intravenous |
Instructions:
|
|
acetazolamide * | 250 mg Four times daily | oral administration |
Instructions:
When required.
|
|
foliNIc acid (as calcium folinate) | 30 mg flat dosing Every six hours | intravenous | 2 minutes |
Instructions:
|
Additional details
Section 1: Further information on pegaspargase
- Pegaspargase (and asparaginase products) should only be administered by centres with appropriate expertise.
- There is limited data available for use of pegaspargase in patients 65 years and older. Strongly consider not using pegaspargase in patients 65 years and older.
- Consideration can be given to reducing dose of pegaspargase to 500 international units/m2 for certain patients.
- Prior to using pegaspargase perform a baseline abdominal ultrasound scan is recommended to examine the biliary tract, pancreas and hepatic echotexture. Pegasparagase is contraindicated in those with a history of severe significant hepatic impairment, including alcoholic liver disease, autoimmune or viral hepatitis, and steatohepatitis/NASH.
- If after pegaspargase there is any evidence of steatosis/liver disease, perform an ultrasound of the liver.
- Development of anti-asparaginase antibodies may be associated with low asparaginase activity levels. As a precaution, periodic measurement of the asparaginase activity level in serum or plasma is recommended.
- Routine monitoring for bone marrow suppression, coagulations abnormalities, pancreatitis, hepatic toxicity, hyperuricaemia, hyperglycaemia, ketoacidosis and hypertriglyceridaemia is required. See Additional information - pegaspargase.
- To reduce risk of hypersensitivity to pegaspargase avoid using other pegylated products e.g. pegFILGRASTIM if there is a suitable non-pegylated form.
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 |
Emetogenicity: | Variable |
Folinic acid rescue for high dose methotrexate: | Mandatory |
Hydration: | Routine hydration recommended |
Hypersensitivity / Infusion related reaction risk: | High - routine premedication recommended |
Pneumocystis jirovecii pneumonia (PJP) prophylaxis: | Routine antibiotic prophylaxis recommended |
Emetogenicity:
- MEDIUM days 1 and 15, high dose metHOTREXATe may be highly emetogenic in certain patients.
- MINIMAL days 2, 3, 16, and 17.
PJP prophylaxis: If trimethoprim + sulfamethoxazole is used as prophylaxis, it is recommended to withhold at least 48 hours prior to high dose metHOTREXATe administration and until serum metHOTREXATe level is less than 0.05 µmol/L – 0.1µmol/L (as per institutional practice).
References
* 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.