To see all protocols that comply with the WHO Essential Medicine List 
  1. Home
  2. Haematology and BMT
  3. Lymphoma
  4. Non-Hodgkin lymphoma

Peripheral T-cell lymphoma pralatrexate

Patients with lymphoma should be considered for inclusion into clinical trials. Link to ALLG website, ANZCTR website and Lymphoma Australia website.

This protocol is based on limited evidence; refer to the evidence section of this protocol for more information.

The anticancer drug(s) in this protocol may have been included in the ADDIKD guideline. Dose recommendations in kidney dysfunction have yet to be updated to align with the ADDIKD guideline. Recommendations will be updated once the individual protocol has been evaluated by the reference committee. For further information refer to the ADDIKD guideline. To assist with calculations, use the eviQ Estimated Glomerular Filtration Rate (eGFR) calculator.

On this page
Expand all Collapse all Back to top

Cycle 1 and further cycles

Drug Dose Route Day
Pralatrexate 30 mg/m2 IV bolus 1, 8, 15, 22, 29, 36
Calcium folinate (Leucovorin) 30 mg THREE times a day PO 2 and 3, 9 and 10, 16 and 17, 23 and 24, 30 and 31, 37 and 38

Notes:

  • Pralatrexate is a powerful folate antagonist, so it is imperative that the patient is kept Vitamin B12 and folate replete. See recommended replacement regimen in the Clinical Information section. This includes a period of pre-treatment prior to the administration of pralatrexate.​
  • It is the consensus of the Haematology Reference Committee to include calcium folinate (leucovorin) to the treatment schedule based on preliminary data suggesting a reduction in the rate and grade of mucositis. Calcium folinate (leucovorin) was administered for 2 consecutive days beginning 24 hours after each dose of pralatrexate.r
  • Please note that the dose of calcium folinate (leucovorin) differs from the study protocol (which used 25 mg) due to tablet strength availability in Australia. 
Frequency:
49 days . Once weekly for six weeks, followed by a one week rest period.
Cycles:
Continuous until disease progression or unacceptable toxicity
Drug status:

Pralatrexate: (PBS authority)

Cost:
~ $18,000 per cycle "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au), MIMS Online and other sources. These costs are reviewed and updated on eviQ at 6 monthly intervals.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 and further cycles

Day 1
Pralatrexate 30 mg/m2 (IV bolus) over 3 to 5 minutes
Day 2 and 3
Calcium folinate (Leucovorin) 30 mg (PO) THREE times a day for 2 days, beginning 24 hours after each pralatrexate dose.
Day 8
Pralatrexate 30 mg/m2 (IV bolus) over 3 to 5 minutes
Day 9 and 10
Calcium folinate (Leucovorin) 30 mg (PO) THREE times a day for 2 days, beginning 24 hours after each pralatrexate dose.
Day 15
Pralatrexate 30 mg/m2 (IV bolus) over 3 to 5 minutes
Day 16 and 17
Calcium folinate (Leucovorin) 30 mg (PO) THREE times a day for 2 days, beginning 24 hours after each pralatrexate dose.
Day 22
Pralatrexate 30 mg/m2 (IV bolus) over 3 to 5 minutes
Day 23 and 24
Calcium folinate (Leucovorin) 30 mg (PO) THREE times a day for 2 days, beginning 24 hours after each pralatrexate dose.
Day 29
Pralatrexate 30 mg/m2 (IV bolus) over 3 to 5 minutes
Day 30 and 31
Calcium folinate (Leucovorin) 30 mg (PO) THREE times a day for 2 days, beginning 24 hours after each pralatrexate dose.
Day 36
Pralatrexate 30 mg/m2 (IV bolus) over 3 to 5 minutes
Day 37 and 38
Calcium folinate (Leucovorin) 30 mg (PO) THREE times a day for 2 days, beginning 24 hours after each pralatrexate dose.

Notes:

  • It is the consensus of the Haematology Reference Committee to include calcium folinate (leucovorin) to the treatment schedule based on preliminary data suggesting a reduction in the rate and grade of mucositis. Calcium folinate (leucovorin) was administered for 2 consecutive days beginning 24 hours after each dose of pralatrexate.r
  • Please note that the dose of calcium folinate (leucovorin) differs from the study protocol (which used 25 mg) due to tablet strength availability in Australia. 

Frequency:
49 days . Once weekly for six weeks, followed by a one week rest period.
Cycles:
Continuous until disease progression or unacceptable toxicity

Cycle 1 and further cycles

Drug Dose Route Day
Pralatrexate 30 mg/m2 IV bolus 1, 8, 15, 22, 29, 36
Calcium folinate (Leucovorin) 30 mg THREE times a day PO 2 and 3, 9 and 10, 16 and 17, 23 and 24, 30 and 31, 37 and 38

Notes:

  • Pralatrexate is a powerful folate antagonist, so it is imperative that the patient is kept Vitamin B12 and folate replete. See recommended replacement regimen in the Clinical Information section. This includes a period of pre-treatment prior to the administration of pralatrexate.​
  • It is the consensus of the Haematology Reference Committee to include calcium folinate (leucovorin) to the treatment schedule based on preliminary data suggesting a reduction in the rate and grade of mucositis. Calcium folinate (leucovorin) was administered for 2 consecutive days beginning 24 hours after each dose of pralatrexate.r
  • Please note that the dose of calcium folinate (leucovorin) differs from the study protocol (which used 25 mg) due to tablet strength availability in Australia. 
Frequency:
49 days . Once weekly for six weeks, followed by a one week rest period.
Cycles:
Continuous until disease progression or unacceptable toxicity
Drug status:

Pralatrexate: (PBS authority)

Cost:
~ $18,000 per cycle "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au), MIMS Online and other sources. These costs are reviewed and updated on eviQ at 6 monthly intervals.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 and further cycles

Day 1
Pralatrexate 30 mg/m2 (IV bolus) over 3 to 5 minutes
Day 2 and 3
Calcium folinate (Leucovorin) 30 mg (PO) THREE times a day for 2 days, beginning 24 hours after each pralatrexate dose.
Day 8
Pralatrexate 30 mg/m2 (IV bolus) over 3 to 5 minutes
Day 9 and 10
Calcium folinate (Leucovorin) 30 mg (PO) THREE times a day for 2 days, beginning 24 hours after each pralatrexate dose.
Day 15
Pralatrexate 30 mg/m2 (IV bolus) over 3 to 5 minutes
Day 16 and 17
Calcium folinate (Leucovorin) 30 mg (PO) THREE times a day for 2 days, beginning 24 hours after each pralatrexate dose.
Day 22
Pralatrexate 30 mg/m2 (IV bolus) over 3 to 5 minutes
Day 23 and 24
Calcium folinate (Leucovorin) 30 mg (PO) THREE times a day for 2 days, beginning 24 hours after each pralatrexate dose.
Day 29
Pralatrexate 30 mg/m2 (IV bolus) over 3 to 5 minutes
Day 30 and 31
Calcium folinate (Leucovorin) 30 mg (PO) THREE times a day for 2 days, beginning 24 hours after each pralatrexate dose.
Day 36
Pralatrexate 30 mg/m2 (IV bolus) over 3 to 5 minutes
Day 37 and 38
Calcium folinate (Leucovorin) 30 mg (PO) THREE times a day for 2 days, beginning 24 hours after each pralatrexate dose.

Notes:

  • It is the consensus of the Haematology Reference Committee to include calcium folinate (leucovorin) to the treatment schedule based on preliminary data suggesting a reduction in the rate and grade of mucositis. Calcium folinate (leucovorin) was administered for 2 consecutive days beginning 24 hours after each dose of pralatrexate.r
  • Please note that the dose of calcium folinate (leucovorin) differs from the study protocol (which used 25 mg) due to tablet strength availability in Australia. 

Frequency:
49 days . Once weekly for six weeks, followed by a one week rest period.
Cycles:
Continuous until disease progression or unacceptable toxicity
  • Peripheral T-cell lymphoma in patients with relapsed or chemotherapy refractory disease
Venous access required

IV cannula (IVC) or central venous access device (CVAD) is required to administer this treatment.

Read more about central venous access device line selection
Vitamin B12 and folate co-administration

Starting within 10 weeks prior to the first dose of pralatrexate: 

Hydroxocobalamin (Vit B12) 1000 micrograms intramuscularly and repeat every 8-10 weeks thereafter. Subsequent Vit B12 injections may be given the same day as pralatrexate.

Starting within the 10 day period preceding the first dose of pralatrexate:

Folic acid 1 mg PO once daily continuously until 30 days after the last dose of pralatrexate. 
Emetogenicity MINIMAL

Antiemetics are not routinely required; however should a patient experience emesis:

Metoclopramide 10 mg three times a day when necessary (maximum of 30 mg/24 hours, up to 5 days) OR

Prochlorperazine 10 mg PO every 6 hours when necessary may be administered.

Read more about preventing anti-cancer therapy induced nausea and vomiting
Dermatological toxicities

Dermatological reactions ranged from alopecia, pruritus, and rash to serious or fatal skin necrosis, skin exfoliation, skin ulceration, toxic epidermal necrolysis (TEN), and bullous eruptions. There have been dermatological toxicities resulting in deaths in both clinical trials and post-marketing setting, they occurred early in treatment and generally after the first dose.  

Patients with extensive skin disease or a history of adverse skin reactions appear to be at highest risk of developing these severe reactions. Skin reactions may be progressive and increase in severity with further treatment. Patients with dermatological reactions should be monitored closely, and if dermatological reactions are severe pralatrexate should be withheld or discontinued.
Mucositis

Mucositis, including stomatitis or mucosal inflammation of gastrointestinal and genitourinary tracts, is a common and potentially SEVERE side effect with this treatment. Early intervention, such as prophylactic calcium folinate (leucovorin), may help to avoid dose alteration or interruption. 

It is IMPERATIVE that prescribers refer to dose modifications for more information before prescribing. 

Monitor for mucosal inflammation weekly and if ≥ Grade 2, omit and/or reduce the dose.
Pneumonitis

Pneumonitis associated with pralatrexate has been reported in patients.

In one case, it was considered to be an acute hypersensitivity reaction to pralatexate.

Monitor patients for signs and symptoms of pneumonitis (e.g. new or worsening cough, shortness of breath, or chest pain).
Third space fluid accumulation

Pralatrexate should be used with caution in patients with third space compartment fluid accumulation (e.g. pleural effusions, ascites or significant peripheral oedema) as its effect is unknown.

In patients with clinically significant third space fluid, consideration should be given to draining the effusion before starting treatment with pralatrexate.
Pneumocystis jirovecii pneumonia (PJP) prophylaxis

PJP prophylaxis is recommended.

Myelosuppression may be exacerbated if trimethoprim/sulfamethoxazole is used in combination with pralatrexate.

Read more about prophylaxis of pneumocystis jirovecii (carinii) in cancer patients
Tumour lysis risk

Assess patient for risk of developing tumour lysis syndrome.

Read more about prevention and management of tumour lysis syndrome.
Growth factor support

G-CSF (short or long-acting) is available on the PBS for chemotherapy induced neutropenia depending on clinical indication and/or febrile neutropenia risk.  

Access the PBS website
Irradiated blood components

The use of irradiated of blood components is recommended for patients receiving this treatment.

Read more about the indications for the use of irradiated blood components
Blood tests

FBC, EUC, LFTs at baseline. Repeat FBC weekly prior to treatment. Repeat EUC, LFTs prior to the start of the first and fourth dose of a given cycle, or more frequently if clinical indicated.
Hepatitis B screening and prophylaxis

Routine screening for HBsAg and anti-HBc is recommended prior to initiation of treatment. Prophylaxis should be determined according to individual institutional policy.

Read more about hepatitis B screening and prophylaxis in cancer patients requiring cytotoxic and/or immunosuppressive therapy
Vaccinations

Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease.

Refer to the recommended schedule of vaccination for immunocompromised patients, as outlined in the Australian Immunisation Handbook.

Read more about COVID-19 vaccines and cancer.
Fertility, pregnancy and lactation

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment. There is a risk of foetal harm in pregnant women. A pregnancy test should be considered prior to initiating treatment in females of reproductive potential if sexually active. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. Effective contraception methods and adequate contraception timeframe should be discussed with all patients of reproductive potential. Possibility of infant risk should be discussed with breastfeeding patients.

Read more about the effect of cancer treatment on fertility
Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the anti-cancer regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information, published guidelines and reference committee consensus . The dose reduction applies to each individual dose and not to the total number of days or duration of treatment cycle unless stated otherwise. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.
The dose recommendations in kidney dysfunction (i.e.renal impairment) displayed may not reflect those in the ADDIKD guideline and have been included for historical reference only. Recommendations will be updated once the individual protocol has been evaluated by the reference committee, with this version of the protocol then being archived. Clinicians are expected to refer to the ADDIKD guideline prior to prescribing in kidney dysfunction.
International Consensus Guideline for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD).

Note: Prior to initiation of any dose: ​

  • Mucositis should be ≤ grade 1
  • ANC should be > 1.0 x 109/L
  • Platelets should be ≥ 100 x 109/L for first dose; and ≥ 50 x 109/L for all subsequent doses

Doses may be omitted or reduced, based on patient tolerance. Omitted doses should not be made up at the end of the cycle. Once a dose reduction occurs for toxicity, the dose should not be re-escalated.

Haematological toxicity
ANC x 109/L (pre-treatment blood test)
0.5 to 1.0 and no fever Omit treatment until ANC > 1.0 and resume at same dose
0.5 to 1.0 with fever
​OR
less than 0.5

Omit treatment until ANC > 1.0 and administer G-CSF.

Reduce the dose for subsequent pralatrexate based on duration or recurrence of toxicity as follows:

1 week: No dose reduction, continue G-CSF support
2 weeks OR 1st recurrence: Reduce pralatrexate to 20 mg/m2 (10 mg/m2 in patients with eGFR 15-30 mL/min) with G-CSF support
3 weeks OR 2nd recurrence: Discontinue pralatrexate permanently.
Platelets x 109/L (pre-treatment blood test)
less than 50

Omit treatment until platelet ≥ 50 and reduce the dose for subsequent pralatrexate based on duration of toxicity as follows:

1 week: No dose reduction
2 weeks: Reduce pralatrexate to 20 mg/m2 (10 mg/m2 in patients with eGFR 15-30 mL/min)
3 weeks: Discontinue pralatrexate permanently.
Renal impairment*
Creatinine clearance (mL/min)

15 to 30 

 Reduce initial dose to 15 mg/m2. If dose reductions for toxicity are necessary, reduce each dose to 10 mg/m2
End stage renal disease Avoid pralatrexate

* Renal dose modifications have been adopted from the US product informationr

Hepatic impairment

There is no formal data in patients with hepatic impairment, use with caution.

LFT abnormalities have been observed after pralatrexate administration and are usually not cause for dose modifications, however persistent LFT abnormalities may indicate liver toxicity and require evaluation. Monitor LFTs during treatment.
Mucositis and stomatitis
Grade 2

Omit treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent pralatrexate as follows:

1st occurrence: No dose reduction
2nd occurrence: Reduce pralatrexate to 20 mg/m2 (10 mg/m2 in patients with eGFR 15-30 mL/min)
Grade 3 Omit treatment until toxicity has resolved to Grade 1 or less and reduce pralatrexate to 20 mg/m2 (10 mg/m2 in patients with eGFR 15-30 mL/min)
Grade 4 Discontinue pralatrexate permanently
Non-Haematological toxicity
Grade 3 Omit treatment until toxicity has resolved to Grade 2 or less and reduce the dose for subsequent pralatrexate to 20 mg/m2 (10 mg/m2 in patients with eGFR 15-30 mL/min)
Grade 4 Discontinue pralatrexate permanently

Drug interactions in eviQ protocols are under review and being updated to align with current literature. Further site-wide updates and changes will occur in due course. References & Disclaimer

The drug interactions shown below are not an exhaustive list. For a more comprehensive list and for detailed information on specific drug interactions and clinical management, please refer to the specific drug product information and the following key resources:  

Pralatrexate
  Interaction Clinical management
Uricosurics (e.g. probenecid) Increased risk of pralatrexate toxicity due to reduced renal excretion

Avoid combination.

If combination is clinically warranted, monitor for pralatrexate toxicity and reduce pralatrexate dose if necessary
Trimethoprim/sulfamethoxazole Increased toxicity of pralatrexate (bone marrow suppression) possible due to additive antifolate activity Avoid combination or monitor for pralatrexate toxicity
NSAIDS

Penicillin

Proton pump inhibitors (e.g. esomeprazole, omeprazole, pantoprazole)		 Increased risk of pralatrexate toxicity as these drugs may effect glomerular filtration and/or renal tubular secretion and reduce the renal excretion of pralatrexate Use with caution. Monitor for pralatrexate toxicity
Nephrotoxic drugs (e.g. aminoglycosides, amphotericin, cisplatin, contrast dye, frusemide, NSAIDs) Additive nephrotoxicity Avoid combination or monitor renal function closely
General
  Interaction Clinical management
Warfarin Anti-cancer drugs may alter the anticoagulant effect of warfarin. Monitor INR regularly and adjust warfarin dosage as appropriate; consider alternative anticoagulant.
Direct oral anticoagulants (DOACs) e.g. apixaban, rivaroxaban, dabigatran

Interaction with both CYP3A4 and P-gp inhibitors /inducers.

DOAC and anti-cancer drug levels may both be altered, possibly leading to loss of efficacy or toxicity (i.e. increased bleeding).

Apixaban: avoid concurrent use with strong CYP3A4 and P‑gp inhibitors. If treating VTE, avoid use with strong CYP3A4 and P‑gp inducers. 

Rivaroxaban: avoid concurrent use with strong CYP3A4 and P‑gp  inhibitors.

Dabigatran: avoid combination with strong P‑gp inducers and inhibitors.

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.
Digoxin Anti-cancer drugs can damage the lining of the intestine; affecting the absorption of digoxin. Monitor digoxin serum levels; adjust digoxin dosage as appropriate.
Antiepileptics Both altered antiepileptic and anti-cancer drug levels may occur, possibly leading to loss of efficacy or toxicity. Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the anti-cancer therapy.
Antiplatelet agents and NSAIDs Increased risk of bleeding due to treatment related thrombocytopenia. Avoid or minimise combination.
If combination deemed essential, (e.g. low dose aspirin for ischaemic heart disease) monitor for signs of bleeding.
Serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs e.g. paroxetine) and serotonin noradrenaline reuptake inhibitors (SNRIs e.g. venlafaxine) Increased risk of serotonin syndrome with concurrent use of 5-HT3 receptor antagonists (e.g. palonosetron, ondansetron, granisetron, tropisetron, dolasetron, etc.) Avoid combination.
If combination is clinically warranted, monitor for signs and symptoms of serotonin syndrome (e.g. confusion, agitation, tachycardia, hyperreflexia).
For more information link to TGA Medicines Safety Update
Vaccines Diminished response to vaccines and increased risk of infection with live vaccines. Live vaccines (e.g. BCG, MMR, zoster and varicella) are contraindicated in patients on immunosuppressive therapy. Use with caution in patients on non-immunosuppressive therapy.
For more information; refer to the recommended schedule of vaccination for cancer patients, as outlined in the Australian Immunisation Handbook

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA website for further information.

Day 1

Approximate treatment time: 30 minutes

General patient assessment prior to each day of treatment.

Oral mucositis assessment tool

Any toxicity grade 2 or greater (except for mucositis which should be ≤ grade 1) may require dose reduction, omission or delay of treatment and review by medical officer before commencing treatment. 

Prime IV line(s).

Insert IV cannula or access TIVAD or CVAD.

  • weigh patient on each visit
  • urinalysis each visit

Pre treatment medication

Administer antiemetics if required

Pralatrexate

  • administer via IV bolus over 3 to 5 minutes
  • via a side port of a freely flowing IV infusion
  • flush with ~50 mL of sodium chloride 0.9%

Continue safe handling precautions until 7 days after completion of drug(s)

Day 2 & 3

This is an oral treatment

Calcium Folinate (Leucovorin) tablets

  • Commence 24 hours after each pralatrexate dose 
  • Administer orally THREE times a day for 2 days 

Day 8

Approximate treatment time: 30 minutes

General patient assessment prior to each day of treatment.

Oral mucositis assessment tool

Any toxicity grade 2 or greater (except for mucositis which should be ≤ grade 1) may require dose reduction, omission or delay of treatment and review by medical officer before commencing treatment. 

Prime IV line(s).

  • weigh patient on each visit
  • urinalysis each visit

Pre treatment medication

Administer antiemetics if required

Pralatrexate

  • administer via IV bolus over 3 to 5 minutes
  • via a side port of a freely flowing IV infusion
  • flush with ~50 mL of sodium chloride 0.9%

Continue safe handling precautions until 7 days after completion of drug(s)

Day 9 & 10

This is an oral treatment

Calcium Folinate (Leucovorin) tablets

  • Commence 24 hours after each pralatrexate dose 
  • Administer orally THREE times a day for 2 days 

Day 15

Approximate treatment time: 30 minutes

General patient assessment prior to each day of treatment.

Oral mucositis assessment tool

Any toxicity grade 2 or greater (except for mucositis which should be ≤ grade 1) may require dose reduction, omission or delay of treatment and review by medical officer before commencing treatment. 

Prime IV line(s).

  • weigh patient on each visit
  • urinalysis each visit

Pre treatment medication

Administer antiemetics if required

Pralatrexate

  • administer via IV bolus over 3 to 5 minutes
  • via a side port of a freely flowing IV infusion
  • flush with ~50 mL of sodium chloride 0.9%

Continue safe handling precautions until 7 days after completion of drug(s)

Day 16 & 17

This is an oral treatment

Calcium Folinate (Leucovorin) tablets

  • Commence 24 hours after each pralatrexate dose 
  • Administer orally THREE times a day for 2 days 

Day 22

Approximate treatment time: 30 minutes

General patient assessment prior to each day of treatment.

Oral mucositis assessment tool

Any toxicity grade 2 or greater (except for mucositis which should be ≤ grade 1) may require dose reduction, omission or delay of treatment and review by medical officer before commencing treatment. 

Prime IV line(s).

  • weigh patient on each visit
  • urinalysis each visit

Pre treatment medication

Administer antiemetics if required

Pralatrexate

  • administer via IV bolus over 3 to 5 minutes
  • via a side port of a freely flowing IV infusion
  • flush with ~50 mL of sodium chloride 0.9%

Continue safe handling precautions until 7 days after completion of drug(s)

Day 23 & 24

This is an oral treatment

Calcium Folinate (Leucovorin) tablets

  • Commence 24 hours after each pralatrexate dose 
  • Administer orally THREE times a day for 2 days 

Day 29

Approximate treatment time: 30 minutes

General patient assessment prior to each day of treatment.

Oral mucositis assessment tool

Any toxicity grade 2 or greater (except for mucositis which should be ≤ grade 1) may require dose reduction, omission or delay of treatment and review by medical officer before commencing treatment. 

Prime IV line(s).

  • weigh patient on each visit
  • urinalysis each visit

Pre treatment medication

Administer antiemetics if required

Pralatrexate

  • administer via IV bolus over 3 to 5 minutes
  • via a side port of a freely flowing IV infusion
  • flush with ~50 mL of sodium chloride 0.9%

Continue safe handling precautions until 7 days after completion of drug(s)

Day 30 & 31

This is an oral treatment

Calcium Folinate (Leucovorin) tablets

  • Commence 24 hours after each pralatrexate dose 
  • Administer orally THREE times a day for 2 days 

Day 36

Approximate treatment time: 30 minutes

General patient assessment prior to each day of treatment.

Oral mucositis assessment tool

Any toxicity grade 2 or greater (except for mucositis which should be ≤ grade 1) may require dose reduction, omission or delay of treatment and review by medical officer before commencing treatment. 

Prime IV line(s).

  • weigh patient on each visit
  • urinalysis each visit

Pre treatment medication

Administer antiemetics if required

Pralatrexate

  • administer via IV bolus over 3 to 5 minutes
  • via a side port of a freely flowing IV infusion
  • flush with ~50 mL of sodium chloride 0.9%

Remove IV cannula and/or deaccess TIVAD or CVAD. 

Continue safe handling precautions until 7 days after completion of drug(s)

Day 37 & 38

This is an oral treatment

Calcium Folinate (Leucovorin) tablets

  • Commence 24 hours after each pralatrexate dose 
  • Administer orally THREE times a day for 2 days 

Discharge Information

Pralatrexate premedication 
  • Premedications as prescribed and written instructions on how to take them:
    • folic acid
    • hydroxycobalamin (vitamin B12)
Prophylaxis medications
  • Prophylaxis medications (if prescribed) i.e. tumour lysis prophylaxis, PJP prophylaxis, antifungals, antivirals.
  • Calcium folinate (leucovorin) tablets with instructions on how to take them if prescribed.
Patient information
  • Ensure patient receives patient information sheet.

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Early (onset days to weeks)
Neutropenia

Abnormally low levels of neutrophils in the blood. This increases the risk of infection. Any fever or suspicion of infection should be investigated immediately and managed aggressively. 

Read more about immediate management of neutropenic fever
Thrombocytopenia

A reduction in the normal levels of functional platelets, increasing the risk of abnormal bleeding.  

Read more about thrombocytopenia
Abdominal pain

Dull ache, cramping or sharp pains are common with some anti-cancer drugs. These are caused by either increased or decreased gastrointestinal motility and can be associated with diarrhoea or constipation.
Constipation
Diarrhoea

Read more about treatment induced diarrhoea
Epistaxis

Acute bleeding from the nostril(s), nasal cavity, or nasopharynx.
Fatigue

Read more about fatigue
Fluid retention and oedema

An excess amount of fluid around the cells, tissues or serous cavities of the body, leading to swelling.
Headache
Hepatotoxicity

Anti-cancer drugs administered either alone or in combination with other drugs and/or radiation may cause direct or indirect hepatotoxicity. Hepatic dysfunction can alter the metabolism of some drugs resulting in systemic toxicity.
Hypokalaemia

Abnormally low levels of potassium in the blood.
Nausea and vomiting

Read more about prevention of treatment induced nausea and vomiting
Oral mucositis

Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following chemotherapy, radiation therapy to the head, neck or oesophagus, and high dose chemotherapy followed by a blood and marrow transplant (BMT).

Read more about oral mucositis
Respiratory tract infection
Skin rash

Anti-cancer drugs can cause a number of changes in the skin with maculo-papular rash the most common type of drug-induced skin reaction. 

Read more about skin rash

Late (onset weeks to months)
Anaemia

Abnormally low levels of red blood cells (RBCs) or haemoglobin in the blood. 

Read more about anaemia
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia

The evidence for the use of single-agent pralatrexate in relapsed/refractory peripheral T-cell lymphoma (PTCL) originated from the PROPEL studyr, an open-label, phase 2 trial of pralatrexate with vitamin B12 and folic acid supplementation in patients with relapsed or refractory PTCL. The primary endpoint was overall response rate (ORR) with secondary endpoints including duration of response, progression-free survival (PFS), and overall survival (OS). This multicentre trial enrolled 115 of which 109 patients were evaluable for efficacy. The median age of the patients was 59 years (range, 21-85 years).  The histopathology per central review included 59 PTLC unspecified, 17 anaplastic large cell lymphoma, 13 angioimmunoblastic T-cell lymphoma, and 12 transformed mycosis fungoides patients. Of the 109 patients eligible for efficacy, 26 did not demonstrate any evidence or response to any prior therapy, while 69 patients did not have evidence of response to their most recent prior therapy. Median prior therapies was 3.

Source Study & Year Published Supports Use Is the dose and regimen consistent with the protocol? Comments 
Phase I/II trial Maruyama et al. 2017r Yes Yes -
Phase II trials O'Connor et al. 2011r Yes Yes -
Guidelines Date published/revised Supports Use Is the dose and regimen consistent with the protocol? Comments
NCCN T-Cell lymphoma Version 1.2021 Yes Yes

-
BCCA Revised: 1 Jan 2021 Yes No Dose escalation strategy used for pralatrexate in cycle 1. Cycles = 28 days with pralatrexate on day 1, 8 and 15 only.
Calcium folinate (Leucovorin) given BD on days 3-6, 10-13 and 17-20.
CCO Dec 2021 Yes No No calcium folinate (Leucovorin).

Efficacy

The overall response rate was 29% (OR) with 11% complete response/complete response unconfirmed (CR/CRu) and 18% partial response (PR). The majority of responding patients attained response quickly, where 63% of all responses occurred within the first cycle of pralatrexate.  Median PFS was 3.5 months (95% CI, 1.7 to 4.8) with a range of 1 day to 23.9 months, and the median OS was 14.5 months (95% CI, 10.6 to 22.5), with a range of 1 to 21.4 months. The median duration of remission was 10.1 months, with greater than 25% of responses lasting longer than 300 days.r

Fig 1: Kaplan-Meier estimates of (C) Progression-free survival (D) overall survival per central reviewr

© Journal of Clinical Oncology 2011

Toxicity

The most common grade 3 or 4 toxicities were thrombocytopenia, mucositis, neutropenia and anaemia. The majority of adverse effects were reversible or manageable by dose modifications, however, 23% of patients discontinued treatment due to adverse effects, most frequently mucositis (6%) and thrombocytopenia (5%).r 

Table 1: Adverse events (safety population) in ≥ 10% of patients r

© Journal of Clinical Oncology 2011

Various strategies have been used to minimise toxicity and therefore maximise exposure to pralatrexate. Preliminary results from a phase 2 study has demonstrated that the addition of calcium folinate (leucovorin) as adjunctive treatment has been shown to reduce the rates of both ≥ Grade 2, and ≥ Grade 3 mucositis.r 

[%id%]
[%title%]
[%abstract%]

Flinders Filters has partnered with eviQ to build reliable, robust search filters to retrieve core high level evidence on topics of significance to eviQ. The project goal is the provision of a sustainable model for evidence retrieval to ensure ongoing currency of content.

These search filters have been developed to retrieve the most up to date evidence from PubMed, in real time, using specifically designed search filters built to meet our needs.   

Searches can be used when a protocol is scheduled for review or at any time you choose. Please click on this link to access the Pubmed searches.

Access Flinders Filters, a division of the Flinders Digital Health Research Centre at Flinders University to read more about research solutions to searching problems.

Troubleshooting

Occasionally the searches may not display correctly or take too long to load (and will eventually timeout). This may be caused by Internet Explorer being unable to handle long URL's. You can rectify this by using Firefox, Safari or Google chrome. It is always a good idea to clear the cache regularly to ensure you are getting the most up to date search.

Feedback

If you identify any new articles that you believe should be included in the content, please use the feedback button below to inform us of the name of the article(s). 

Version 2

Date Summary of changes
25/05/2018 New protocol taken to eviQ Lymphoma + CLL meeting.
28/11/2018 New protocol published on eviQ. v.1.
18/07/2019 Calcium folinate (leucovorin) added to the treatment schedule. Version number changed to v.2.
13/09/2019 Reviewed by Haematology Reference Committee with minor changes, review in 2 years.
22/10/2021 Reviewed by Haematology Reference Committee; next review due in 2 years.
08/02/2022 PJP prophylaxis clinical information block updated.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

Send feedback for this page

First approved:
Last reviewed:
Review due:

The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/3455

31 Mar 2023