BC Cancer Protocol Summary for Therapy of Acute Myeloid Leukemia

using azaCITIDine and Venetoclax

Protocol Code ULKAMLAVEN

Tumour Group Leukemia/BMT

Contact Physicians Dr. David Sanford

ELIGIBILITY:
Patients must have:
 Acute myeloid leukemia (AML), previously untreated,
 Ineligible for standard intensive induction chemotherapy:
 Age 75 years or older with ECOG 0-2, or
 Age less than 75 years with significant comorbidities or ineligible for transplant, and
 A Compassionate Access Program (CAP) approval prior to the initiation of treatment

Note: Patients who initiated azacitidine within 6 months may switch to combination therapy with
venetoclax if disease has not progressed.

EXCLUSION:
Patients must not have:
 Acute promyelocytic leukemia (APL)
 Advanced hepatic tumors

CAUTION:
 White blood cell (WBC) count greater than 25 x 109/L (cytoreduction with hydroxyurea
permitted)
 Concurrent therapy with moderate or strong CYP3A4 inhibitors (see dose modifications)
 Creatinine clearance less than 30 mL/min
 Bilirubin greater than 3 x upper limit of normal (ULN)

TESTS:
 Baseline (within 72 h of first treatment): CBC and differential, platelets, sodium, potassium,
chloride, serum bicarbonate, calcium, magnesium, phosphate, uric acid, creatinine, urea,
bilirubin, ALT, LDH, GGT, alkaline phosphatase, albumin, INR, PTT, pregnancy test prior to
treatment in females of child-bearing potential
 Baseline: HIV, HBsAg, HBsAb, HBcAb, HCAb, HSV1 and 2 Ab, VZV
 Cycle 1:
 Tumour lysis syndrome (TLS) monitoring: potassium, calcium, phosphate, uric acid,
creatinine, LDH, albumin
 Inpatient (higher risk for TLS): Q8H on days 1 to 4, starting prior to first dose of
venetoclax
 Outpatient (lower risk for TLS): Prior to treatment on days 1 to 4 (prescriber
responsible to monitor results and advise on supportive treatment)
 Days 1 to 4: CBC and differential, platelets (prescriber responsible to monitor results
and advise on supportive treatment)
 Days 8, 11, 15, 18, 22, 25: CBC and differential, platelets, creatinine, sodium,
potassium, chloride, serum bicarbonate, bilirubin, ALT, alkaline phosphatase, GGT,
LDH, INR, PTT
BC Cancer Protocol Summary ULKAMLAVEN Page 1 of 10
Activated: 1 May 2022 Revised: 1 June 2022 (eligibility updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use.
 Subsequent cycles:
 Prior to each cycle: CBC and differential, platelets, creatinine, sodium, potassium,
chloride, serum bicarbonate, bilirubin, ALT, alkaline phosphatase, GGT, LDH, INR, PTT
 Weekly on Days 8, 15, and 22: CBC and differential, platelets, creatinine, sodium,
potassium, chloride, serum bicarbonate, bilirubin, ALT, alkaline phosphatase, GGT,
LDH, INR, PTT
 It is recommended to arrange bone marrow aspirate and biopsy approximately day 22 to 28
following cycle 1. Best response with this combination occurs within 1-2 cycles in most
patients, and this guides the timing of cycle 2 if count recovery has not occurred at this time.

PREMEDICATIONS:
 Antiemetic protocol for low-moderate emetogenic chemotherapy (see SCNAUSEA)
 ondansetron 8 mg PO 30 minutes prior to azaCITIDine
 If required: prochlorperazine 10 mg PO 30 minutes prior to azaCITIDine

SUPPORTIVE MEDICATIONS:

Tumour lysis syndrome (TLS) may occur with venetoclax. Patients should be assessed for level
of TLS risk. For patients with high risk factors for TLS (e.g. elevated WBC >25 x 109/L at
presentation, extramedullary disease, elevated LDH, hyperuricemia, elevated creatinine or
spontaneous TLS present prior to starting treatment, chronic renal impairment) should be
planned for increased laboratory monitoring and hospitalization for treatment initiation during the
ramp-up phase until 24 hours after reaching maximum venetoclax dose.

TLS prophylaxis:
 WBC count should be less than 25 x 109/L prior to starting venetoclax. Cytoreduction may
be required
 Hydration: Start 48 h prior to 1st dose, and continue throughout initial dose ramp-up phase
 1.5 to 2 L daily (8 glasses) orally, and consider additional IV fluids as needed
 Anti-hyperuricemic agents: Start 48 to 72 h prior to 1st dose
 Allopurinol 300 mg PO daily for 7 days or until dose ramp-up complete and at
physician discretion
 Consider rasburicase 3 mg IV x 1, may repeat Q24H prn
 For patients on rasburicase, blood sample for uric acid must be placed on ice
while awaiting assay
 Correct preexisting blood chemistry abnormalities prior to treatment initiation

Antimicrobial prophylaxis:
 If HBsAg or HBcoreAb positive, start lamiVUDine 100 mg PO daily for the duration of
chemotherapy and continue for one year from treatment completion for patients who are
HBsAg positive and for six months for patients who are HBcoreAb positive.
 Antifungal and anti-bacterial prophylaxis is recommended if ANC less than 0.5 x 109/L
during cycle 1. This should also be considered during subsequent cycles if prolonged
neutropenia occurs. Recommended prophylactic agents include fluconazole 400 mg PO
daily (venetoclax dose modification required – see drug interactions section below) and
levofloxacin 500 mg PO daily. Physician may select alternatives based on organ function,
allergy status, etc.
 If HSV or VZV seropositive: valACYclovir 500 mg PO BID for duration of treatment

BC Cancer Protocol Summary ULKAMLAVEN Page 2 of 10

Activated: 1 May 2022 Revised: 1 June 2022 (eligibility updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use.
TREATMENT:

Cycle 1:
(Outpatients must start on a Monday or Tuesday)
BC Cancer Administration
Drug Dose
Guideline

Standard regimen (preferred):

75 mg/m2/d on days 1 to 7
OR
azaCITIDine subcutaneous*
Alternative regimen (if treatment must be
interrupted by weekends†):
75 mg/m2/d on days 1 to 5, 8 and 9

Ramp-up:
100 mg on day 1, then
venetoclax¥ PO
200 mg on day 2, then
400 mg daily on days 3 to 28

* Administer doses greater than 4 mL as two syringes at two separate sites

† May interrupt for more than 2 days but every effort should be made to avoid scheduling over
long weekends (e.g. over 3-4 days) or statutory holidays during the week. If unavoidable, should
aim to deliver a total of 7 days of treatment out of about 10 consecutive days; having breaks in
therapy over these circumstances do not require CAP approval.

¥ Dose modifications are required for concomitant use of strong or moderate CYP3A4 inhibitors
– see drug interactions section below.

Cycle 2 onwards:
BC Cancer Administration
Drug Dose
Guideline

Standard regimen (preferred):

75 mg/m2/d on days 1 to 7
OR
azaCITIDine subcutaneous*
Alternative regimen (if treatment must be
interrupted by weekends†):
75 mg/m2/d on days 1 to 5, 8 and 9

venetoclax¥ 400 mg daily on days 1 to 28 PO

BC Cancer Protocol Summary ULKAMLAVEN Page 3 of 10

Activated: 1 May 2022 Revised: 1 June 2022 (eligibility updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use.
* Administer doses greater than 4 mL as two syringes at two separate sites

† May interrupt for more than 2 days but every effort should be made to avoid scheduling over
long weekends (e.g. over 3-4 days) or statutory holidays during the week. If unavoidable, should
aim to deliver a total of 7 days of treatment out of about 10 consecutive days; having breaks in
therapy over these circumstances do not require CAP approval.

¥ Dose modifications are required for concomitant use of moderate or strong CYP3A4 inhibitors
– see drug interactions section below.

Repeat every 28 days until disease progression or unacceptable toxicity

DOSE MODIFICATIONS:

Dosing levels:
azaCITIDine
Starting dose 75 mg/m2
Dose level -1 50 mg/m2
Dose level -2 37.5 mg/m2

1. Tumour Lysis Syndrome (TLS)

If patient meets criteria for clinically significant laboratory or clinical TLS, no additional venetoclax
dose should be administered until resolution. During ramp-up, monitor for evidence of TLS, and
manage abnormalities of creatinine and electrolytes promptly

 Changes in blood chemistries that require prompt management can occur as early as 6
to 8 hours after the first dose of venetoclax and after each dose increase
 Reduced renal function (CrCl ≤ 80 mL/min) increases the risk for TLS
 Electrolytes must be corrected to within normal limits prior to proceeding with next dose
of venetoclax during the ramp-up phase
 See Appendix I for TLS management strategies

BC Cancer Protocol Summary ULKAMLAVEN Page 4 of 10

Activated: 1 May 2022 Revised: 1 June 2022 (eligibility updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use.
2. Hematological

It is generally not suggested to interrupt treatment due to cytopenias prior to achieving

remission.

After remission is achieved:

For Day 1 treatment:

Platelets
ANC (x109/L) Doses (both drugs)
(x109/L)

Greater than or Greater than

and 100 %
equal to 1.0 or equal to 50

Less than 1.0 or Less than 50 Delay

During cycle:
Platelets
ANC (x109/L) Doses (both drugs)
(x109/L)

First occurrence, lasting 7 days or longer:

Hold until recovery to Grade 2 or better (ANC > 1.0
and platelets > 50); then resume same dose.
Subsequent occurrence, lasting 7 days or longer:
Hold until recovery to Grade 2 or better (ANC > 1.0
and platelets > 50); then resume same dose but
reduce venetoclax duration by 7 days during each
subsequent cycle (e.g. for the second occurrence
Less than 0.5 or Less than 25
reduce to 21 days instead of 28 days, for the third
occurrence reduce to 14 days, for the fourth
occurrence reduce to 7 days).
For third occurrence or greater, consider reduction
of azaCITIDine by one dose level. In this instance,
it can be considered to increase the cycle dosing
interval to 5 or 6 weeks. Growth factor support
with GCSF can be used following remission to
hasten ANC recovery.

3. Drug Interactions
Venetoclax is a major CYP3A4 substrate and a substrate of P-glycoprotein. Concurrent
administration of drugs which are strong or moderate CYP3A4 inhibitors increases
venetoclax exposure and risk of toxicities, including the risk for TLS at initiation and during
ramp-up. Venetoclax dose modifications during initiation, ramp-up and post ramp-up are
required.

BC Cancer Protocol Summary ULKAMLAVEN Page 5 of 10

Activated: 1 May 2022 Revised: 1 June 2022 (eligibility updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use.
 CYP3A4 inducers may decrease serum concentration of venetoclax.
P-glycoprotein inhibitors (P-gp) may increase serum concentration of venetoclax.

Agent Initiated At initiation and dose ramp-up After dose ramp-up is completed

Strong CYP3A4 Avoid if possible, but if • Reduce venetoclax dose by 75%.

inhibitors unavoidable, reduce venetoclax • Monitor patients more closely for
dose by at least 75% as follows: signs of toxicities.
(e.g. posaconazole,
voriconazole, Day 1 – 10 mg • Resume standard venetoclax
clarithromycin, ritonavir) Day 2 – 20 mg dosing 2 to 3 days after CYP3A4
Day 3 – 50 mg inhibitor is discontinued.
Day 4 – 100 mg or less
Moderate CYP3A4 Avoid if possible, but if • Reduce venetoclax dose by at
inhibitors unavoidable, reduce venetoclax least 50%.
dose by at least 50% as follows: • Monitor patients more closely for
(e.g. fluconazole,
isavuconazole, Day 1 – 50 mg signs of toxicities.
ciprofloxacin, diltiazem) Day 2 – 100 mg • Resume standard venetoclax
Day 3 – 200 mg or less dose 2 to 3 days after CYP3A4
inhibitor is discontinued.

Weak CYP3A4 No dose adjustment needed

inhibitors

Strong and moderate Avoid. Consider alternative treatments with less CYP3A4 induction.
CYP3A4 inducers
(e.g. rifampin,
phenytoin,
carbamazepine)

P-glycoprotein • Avoid if possible, but if unavoidable, reduce venetoclax dose by at

inhibitors least 50%.
(e.g. clarithromycin, • Monitor patients more closely for signs of toxicities.
cyclosporine) • Resume standard dose 2 to 3 days after discontinuation of P-gp
inhibitor.
Note: an exception is made for azithromycin, where dose
adjustments of venetoclax are not required.

BC Cancer Protocol Summary ULKAMLAVEN Page 6 of 10

Activated: 1 May 2022 Revised: 1 June 2022 (eligibility updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use.
4. Non-Hematological:
Severity Venetoclax Dose azaCITIDine Dose
Grade 2 or less 100 % 100 %
Hold if not resolved with supportive Hold until improves to Grade 1 or
Grade 3 or greater care. Once improves to Grade 1 or baseline, then resume at reduced
baseline, resume same dose dose

5. Hepatic:
azaCITIDine: Has not been studied in patients with hepatic impairment.
Venetoclax: No dose modifications for mild or moderate hepatic impairment. A 50% dose
reduction of venetoclax during and after the ramp-up period as well as more frequent
monitoring for signs of toxicity are recommended for patients with severe hepatic impairment.

6. Renal:
azaCITIDine: If increases in BUN or serum creatinine (unexplained) occur, delay until
improves to baseline or normal, then reduce dose by 50% for next treatment course.
Venetoclax: No dose modifications for mild or moderate renal impairment (CrCl 30 mL/min).
Dosing has not been determined for severe renal impairment or patients on dialysis.

7. Gastrointestinal toxicity:
Severity azaCITIDine Dose

Grade 0 – 2 100 %
Grade 3 or greater Reduce one dose level

PRECAUTIONS:
1. Tumour lysis syndrome (TLS): TLS has been reported and the risk is greatest during the
venetoclax dose ramp-up phase. All patients require prophylaxis for TLS using hydration
beginning 48 hours and anti-hyperuricemic agents beginning 48 to 72 hours prior to initiation
of therapy. Hospitalization may be considered for those with additional risk factors for TLS
(elevated WBC >25 x 109/L at presentation, extramedullary disease, elevated LDH,
hyperuricemia, elevated creatinine or spontaneous TLS present prior to starting treatment,
CrCl ≤ 80 mL/min, unable to drink 1.5-2 L per day, unsuitable for outpatient treatment and
lab monitoring, or at physician discretion). It is mandatory that electrolytes are monitored as
TLS requires prompt management (see Appendix I for management recommendations).
2. Neutropenia: The combination of azaCITIDine and venetoclax can often result in more
severe thrombocytopenia and neutropenia of longer duration as compared to single agent
azaCITIDine. As such, patients may be at increased risk for infectious complications and
possibly bleeding events, particularly during the first 1-2 cycles prior to achieving remission.
In case of worsening cytopenias that do not resolve between cycles, bone marrow exam is
recommended to assess if related to disease progression versus drug-effect. It is
recommended to start antibiotic and antifungal prophylaxis when ANC < 0.5 x109/L and
HSV/VZV prophylaxis while on treatment to prevent infection. Fever or other evidence of
BC Cancer Protocol Summary ULKAMLAVEN Page 7 of 10
Activated: 1 May 2022 Revised: 1 June 2022 (eligibility updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use.
 infection must be assessed promptly and treated aggressively. Refer to BC Cancer Febrile
Neutropenia Guidelines. Following the attainment of remission, in patients with febrile
neutropenia and evidence of moderate to severe infection it is suggested to temporarily hold
venetoclax treatment until this is treated.
3. Hepatitis B Reactivation: All patients should be tested for both HBsAg and HBcoreAb. If
either test is positive, such patients should be treated with lamiVUDine 100 mg PO daily for
the entire duration of chemotherapy and continue for one year from treatment completion for
patients who are HBsAg positive and for six months for patients who are HBcoreAb positive.
Such patients should also be monitored with frequent liver function tests and hepatitis B
virus DNA every two months. If the hepatitis B virus DNA level rises during this monitoring,
management should be reviewed with an appropriate specialist with experience managing
hepatitis and consideration given to halting chemotherapy.
4. Hepatotoxicity: azaCITIDine may be hepatotoxic, with progressive hepatic coma leading to
death having been rarely reported in patients with extensive tumor burden, especially those
with a baseline albumin less than 30 g/L. It is contraindicated in patients with advanced
malignant hepatic tumours.
5. Renal toxicity: azaCITIDine in combination with chemotherapy have been associated with
serum creatinine elevations, renal tubular acidosis, and renal failure.
6. Drug interactions: Venetoclax is a major CYP3A4 substrate and a substrate of P-
glycoprotein. Concurrent administration of drugs which are strong or moderate CYP3A4
inhibitors should be avoided during initiation and during the dose ramp-up phase, due to
increased serum concentration of venetoclax and potential increased risk of TLS. See Drug
Interactions in Dose Modification section above.
7. Pregnancy: Venetoclax is not recommended for use in pregnancy. Fetotoxicity is likely.
Women of childbearing potential should undergo pregnancy testing before initiating
treatment and use adequate contraception during treatment and for at least 30 days after
the last dose.
8. GI Toxicity: azaCITIDine is associated with GI toxicity including nausea, vomiting, diarrhea,
and constipation. Use of prophylactic 5-HT3 antagonists (e.g. ondansetron) is also
associated with constipation. Patients should be made aware of potential GI toxicities prior
to starting azaCITIDine.

Call Dr. David Sanford or tumour group delegate at (604) 877-6000 or 1-800-663-3333 with
any problems or questions regarding this treatment program.

References:
1. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute
myeloid leukemia. N Engl J Med 2020; 383(7):617-29.
2. AbbVie Corporation. VENCLEXTA® product monograph. St-Laurent, Quebec; 21 January 2021
3. AbbVie Inc. VENCLEXTA® product monograph. North Chicago, IL; December 2021.
4. Howard et al. the Tumor Lysis Syndrome. NEJM 2011; 364(19): 1844-1854
5. Coiffer et al. Guidelines for the Management of Pediatric and Adult Tumor Lysis Syndrome: An
Evidence-Based Review. JCO 2008; 26(16): 2767-2778
6. Tumor Lysis Syndrome (TLS) in Adult Patients from MD Anderson Centre.
https://www.mdanderson.org/content/dam/mdanderson/documents/for-physicians/algorithms/clinical-
management/clin-management-tumor-lysis-web-algorithm.pdf
7. Agarwal et al. Effect of Azithromycin on Venetoclax Pharmacokinetics in Health Volunteers:
Implications for Dosing Venetoclax with P-gp Inhibitors. Advances in Therapy 2018; 35(11):2015-
2023

BC Cancer Protocol Summary ULKAMLAVEN Page 8 of 10

Activated: 1 May 2022 Revised: 1 June 2022 (eligibility updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to
apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at
your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use.
APPENDIX I:

Manage Tumour Lysis Syndrome (TLS) according to institution guidelines. If no local guidelines, may use the following.
Consider hospital admission, if needed for cardiac monitoring or IV medications/hydration.

Suggested Guide for Management of Tumour Lysis Syndrome (TLS) (adapted from MD Anderson TLS guidelines6)

Electrolyte Abnormality Management Recommendations

Hyperkalemia

Mild Restrict potassium intake (avoid IV and PO potassium, limit dietary intake)
•
Sodium polystyrene (Kayexalate®)
•
(greater than upper limit of normal to o 15-30 grams PO
less than 6 mmol/L) o Repeat as needed depending on follow-up potassium levels
• Consider ECG and cardiac rhythm monitoring at physician discretion
Moderate • Restrict potassium intake (avoid IV and PO potassium, limit dietary intake)
• ECG and cardiac rhythm monitoring
(6-7 mmol/L) and asymptomatic • Sodium polystyrene (Kayexalate®)
o 15-30 grams PO
o Repeat every 4 to 6 hours depending on follow-up potassium levels
Severe Same as moderate plan plus:
• Concurrent ECG changes: calcium gluconate 1 g via slow IV infusion; may be repeated after 5-10
(greater than 7 mmol/L and/or minutes if ECG changes persist
symptomatic) • To temporarily shift potassium intracellularly:
• IV insulin and dextrose
 Give 10 units of regular insulin in 500 mL of D10W infused IV over 60 minutes
 Monitor blood glucose closely
• Sodium bicarbonate
 Give 50 mEq via slow IV infusion
 Can be used if patient is acidemic; however sodium bicarbonate and calcium
should not be administered through the same lumen
• Salbutamol
 Give 10-20 mg in 4 mL saline via nebulizer over 20 minutes or 10-20 puffs via
inhaler over 10-20 minutes
 Avoid in patients with acute coronary disease
BC Cancer Protocol Summary ULKAMLAVEN Page 9 of 10
Activated: 1 May 2022 Revised: 1 June 2022 (eligibility updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of
individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use.
 Electrolyte Abnormality Management Recommendations

Hyperphosphatemia

Moderate • Restrict phosphorus intake (avoid IV and PO phosphorus; limit dietary sources)
(greater than or equal to 1.94 mmol/L) • Administer phosphate binder:
o Sevelamer (Renagel®, Renvela®) 800-1600 mg PO three times a day with meals
o Lanthanum carbonate (Fosrenol®) 500-1000 mg PO three times a day with meals
o Aluminum hydroxide tablet 300 mg PO three times a day with meals, may increase dose
to 600 mg PO three times a day (avoid in patients with renal dysfunction)
o Aluminum hydroxide 64 mg/mL suspension 15 mL PO three times a day with meals,
may increase dose to 30 mL four times a day based on phosphate level (avoid in
patients with renal dysfunction)
Severe Dialysis may be needed in severe cases

Hypocalcemia (calcium less than or equal to 1.75 mmol/L or ionized calcium less than or equal to 0.8 mmol/L)

Asymptomatic • No therapy
• To avoid calcium phosphate precipitation, asymptomatic patients with acute hypocalcemia and
hyperphosphatemia should not be given calcium repletion until phosphorous level has
normalized
Symptomatic Calcium gluconate 1 g via slow IV infusion with ECG monitoring

Uremia (renal dysfunction)

• Fluid and electrolyte management

• Uric acid and phosphate management
• Adjust doses for renally excreted medications
• Dialysis

BC Cancer Protocol Summary ULKAMLAVEN Page 10 of 10

Activated: 1 May 2022 Revised: 1 June 2022 (eligibility updated)
Warning: The information contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of
individual clinical circumstances to determine any patient's care or treatment. Use of these documents is at your own risk and is subject to BC Cancer's terms of use available at www.bccancer.bc.ca/terms-of-use.