regimen-monograph

CHLO+OFAT

Intent

Palliative

Regimen Category

Emergent

Funding Program

ODB - General Benefit

Drugs Used

oFAtumumab , chlorambucil

A - Regimen Name

CHLO+OFAT Regimen

Chlorambucil-Ofatumumab

Disease Site

Hematologic - Leukemia - Chronic Lymphocytic (CLL)

Intent

Palliative

Regimen Category

Emergent :

Regimens that may eventually be ‘evidenced informed’, but are still undergoing review. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.

Rationale and Uses

For the treatment of chronic lymphocytic leukemia (CLL) in patients who have not received prior therapy and for whom fludarabine-based therapy is considered inappropriate. (Health Canada indication)

Supplementary Public Funding

chlorambucil
ODB - General Benefit (chlorambucil) (

ODB Formulary

)

B - Drug Regimen

oFAtumumab

Cycle Number	Steroid Premedication with each infusion	Ofatumumab Dose
1 (day 1)	Full dose*	300 mg
1 (day 8)	Full dose*	1000 mg
2-12^** (q 28 days)	Decreased in each cycle if no prior Grade 3/4 infusion reaction	1000 mg q 28 days

_{*prednisolone 50 mg or equivalent
**In the clinical trial, patients received treatment for a minimum of 3 cycles until best response, up to a maximum of 12 cycles}

chlorambucil

10 mg /m²

Days 1 to 7

C - Cycle Frequency

REPEAT EVERY 28 DAYS

For a maximum of 12 cycles unless disease progression or unacceptable toxicity occurs

D - Premedication and Supportive Measures

Antiemetic Regimen:

Minimal

Patients at risk of tumour lysis syndrome should be considered for prophylaxis 12-24 hours prior to ofatumumab infusion and be monitored closely.

Premedications (give 30 – 120 minutes prior):

• acetaminophen 1000 mg
• oral or IV antihistamine (diphenhydramine 50 mg or cetirizine 10 mg or equivalent)
• IV corticosteroid (prednisolone 50 mg or equivalent)

E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. The following recommendations are from product monographs and may be considered.

No dose reductions are recommended for ofatumumab. The infusion may be discontinued, held or its rate reduced as appropriate. Do not re-escalate reduced doses of chlorambucil.

Dosage with toxicity

Toxicity	Ofatumumab dose*	Chlorambucil dose (% previous dose)**
Grade 3 or 4 hematologic toxicity, febrile neutropenia or thrombocytopenic bleeding	Consider hold	Hold*, then ↓ 33% or discontinue
Grade 3 related organ/non-hematologic toxicity	No change	Hold*, then ↓ 33%
Grade 4 related organ/non-hematologic toxicity, severe skin reaction, pneumonitis (any grade), severe arrhythmias or other cardiac events	Discontinue	Discontinue
GI obstruction	Hold. Investigate and manage appropriately
Viral hepatitis or other serious infections	Discontinue	Discontinue
PML	Discontinue and refer to neurologist for diagnosis and treatment
Infusion reaction (IR) Grade 1-2	Hold. Restart at half the infusion rate (but not slower than 12 mL/hr) when patient is stable	Not applicable
IR Grade 3	Hold until stable - restart at 12 mL/hr when patient is stable (do not exceed doubling rate every 30 mins)	Not applicable
IR Grade 4	Discontinue	Not applicable

_{* Missed or delayed doses may be administered later at MD discretion
**Before retreatment, major organ toxicities should recover to ≤ grade 2, platelets ≥ 100 x 10⁹/L, and ANC ≥ 1.5 x 10⁹/L}

Hepatic Impairment

Elimination of ofatumumab is not restricted to hepatic tissue therefore hepatic impairment is unlikely to require dosage modification. Dosage adjustment is recommended for chlorambucil in severe hepatic impairment (no details found).

Renal Impairment

CrCl (ml/min)	Ofatumumab dose	Chlorambucil dose (% usual dose)
30-50	No adjustment needed	75%
10-29	No data. Use with extreme caution or avoid	75%
< 10	No data. Use with extreme caution or avoid	50%

F - Adverse Effects

Refer to ofatumumab, chlorambucil drug monograph(s) for additional details of adverse effects

Most Common Side Effects	Less Common Side Effects, but may be Severe or Life-Threatening
Cough, dyspnea Myelosuppression ± infection, bleeding (may be severe, prolonged) Immunosuppression (opportunistic infections, viral, TB reactivation) Rash (may be severe) Diarrhea Fatigue Nausea, vomiting Edema Musculoskeletal pain	Hypersensitivity Arrhythmia Tumour lysis syndrome Arterial thromboembolism Venous thromboembolism GI obstruction Leukoencephalopathy (PML) Secondary malignancy Neurotoxicity Hepatotoxicity Pneumonitis

G - Interactions

Refer to ofatumumab, chlorambucil drug monograph(s) for additional details

H - Drug Administration and Special Precautions

Refer to ofatumumab, chlorambucil drug monograph(s) for additional details

I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

Cardiac tests for all patients with cardiac risk factors; baseline and periodic
CBC; baseline and before each dose and as clinically indicated after treatment completion
Liver and renal function tests; baseline and regular
Clinical toxicity assessment for infusion reactions, cardiac events (especially in patients with cardiac risk factors) infection, bleeding, neurotoxicity, respiratory, GI, skin, pulmonary toxicities; regular
Hepatitis B screening prior to treatment for all patients. Monitor for signs and symptoms of hepatitis B during treatment. Seropositive patients should see hepatologist and be closely monitored for several months after the last infusion.
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

J - Administrative Information

Outpatient prescription for home administration (chlorambucil)

K - References

Chlorambucil and ofatumumab drug monographs, Cancer Care Ontario.

Hillmen P, Robak T, Janssens A, et al. Ofatumumab + chlorambucil versus chlorambucil alone in patients with untreated chronic lymphocytic leukemia (CLL). Results of the Phase III Study COMPLEMENT 1 (abstract).

M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.

Last Updated: July 21, 2026

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