Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
ALEM+RITU
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
For the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL)
Week 1:
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alemtuzumab a, b, c | 3 mg | IV / Subcut | (first dose) |
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alemtuzumab a, b, c | 10 mg | IV / Subcut | (second dose) |
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alemtuzumab a, b, c | 30 mg | IV / Subcut | (third dose) |
| (This drug is not publicly funded. Universal compassionate access program is available. ) | |||
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Weeks 2 to 13: |
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alemtuzumab a, b, c | 30 mg | IV / Subcut | 3 times per week |
| (This drug is not publicly funded. Universal compassionate access program is available. ) | |||
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riTUXimab d | 375 mg /m² | IV | Once weekly for 4 weeks |
| (This drug is not currently publicly funded for this regimen and intent) | |||
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Note: Different rituximab products are NOT INTERCHANGEABLE. |
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a. Although not approved by Health Canada, alemtuzumab has been given subcutaneously instead of intravenously; the incidence of infusion reactions may be lower.
b. Gradual dose escalation is required at the initiation of therapy and after treatment interruptions of 7 days or more. In most patients, escalation to 30mg can be accomplished in 3-7 days. Initial doses can be administered in various ways; sequentially (daily on days 1 to 3) and on alternate days (i.e. days 1, 3, and 5). Both schedules were used in clinical trials.
c. Single doses of alemtuzumab greater than 30 mg or cumulative weekly doses of greater than 90 mg should not be administered since higher doses are associated with an increased incidence of pancytopenia.
d. The rituximab dose may be split over 2 days for patients with elevated absolute lymphocyte counts.
Alemtuzumab: For a usual total of 13 weeks (1 week dose escalation, 12 weeks maintenance) unless disease progression or unacceptable toxicity occurs.
Rituximab: For a usual total of 4 weeks unless disease progression or unacceptable toxicity occurs.
Minimal
Other Supportive Care:
Pre-medication (prophylaxis for infusion reactions):
Administer at least 30 minutes prior to treatment:
- H1-receptor antagonist (e.g. diphenhydramine 50 mg IV)
- Acetaminophen 650 mg PO
- Corticosteroid:
- Alemtuzumab: Can consider corticosteroids (methylprednisolone 1g) on the first 3 days
- Rituximab: Corticosteroid (for example, methylprednisolone 80 mg IV) in patients with high bulk disease or pulmonary involvement if no corticosteroids are already being given as part of the chemotherapy regimen.
Other supportive care:
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Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
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Allopurinol and hydration to reduce the risk of tumour lysis syndrome are recommended.
- Trimethoprim/sulfamethoxazole DS twice daily three times per week and famciclovir (or equivalent) 250mg bid during treatment and for 2 months after or until CD4+ count is ≥ 200 cells/microL.
- Consider prophylaxis with G-CSF for patients at risk of febrile neutropenia.
- Irradiated blood products should be used.
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
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Toxicity (grade or 109)
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1st Occurrence*
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2nd Occurrence*
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3rd Occurrence
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ANC < 0.25 and/or
platelet ≤ 25
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Hold, restart at same dose when ANC ≥ 0.5 and platelets ≥ 50
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Hold, restart at 10mg when ANC ≥ 0.5 and platelets ≥ 50
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Discontinue
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If baseline ANC ≤ 0.25, and/or platelet ≤ 25 and ↓ 50%
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Hold, restart at same dose when ≥ baseline
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Hold, restart at 10mg when ≥ baseline
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Discontinue
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≥ Grade 3 non-hematologic toxicity, including serious infections and CMV viremia
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Hold until ≤ grade 2. Consider dose modification
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Autoimmune disorders
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Discontinue
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PML, autoimmune anemia or thrombocytopenia
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Discontinue
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*If delay between dosing is ≥ 7 days, must re-escalate starting from 3mg
Do not modify dose for lymphopenia
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Rituximab:
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Toxicity
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Rituximab Dose** / Infusion Rate
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Myelosuppression
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No adjustment required.
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Other grade 3 toxicity
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Delay infusion until ≤ grade 2
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Discontinue
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**Missed or delayed doses may be administered at a later time point, based on physician’s discretion. |
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Management of administration-related reactions:
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Rituximab IV:
| Grade | Management | Re-challenge |
| 1 or 2 |
Restart:
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| 3 or 4 |
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Alemtuzumab:
| Grade | Management | Re-challenge |
| 1-2 |
Restart:
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| 3-4 |
Restart:
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Hepatic Impairment
No dosage adjustment required for rituximab. Discontinue if evidence of hepatitis. No information available for alemtuzumab.
Renal Impairment
No dosage adjustment required for rituximab. No information available for alemtuzumab.
Dosage in the Elderly
No dosage adjustment required. Limited experience with alemtuzumab. For rituximab, older patients are more likely to experience serious adverse events (including cardiac, pulmonary, or other grade 3 or 4 toxicity).
Refer to alemtuzumab, riTUXimab drug monograph(s) for additional details of adverse effects
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Very common (≥ 50%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
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Refer to alemtuzumab, riTUXimab drug monograph(s) for additional details
- Consider withholding antihypertensive medication 12 hours prior to and during rituximab administration
- Additive effects with medications that can cause hypotension (especially at time of alemtuzumab infusion)
Additive effects with medications that can increase risk of bleeding when used with alemtuzumab
Refer to alemtuzumab, riTUXimab drug monograph(s) for additional details
Note: Different rituximab products are NOT INTERCHANGEABLE.
Rituximab IV and Subcutaneous formulations are not interchangeable. The dosing and concentrations of these products are different.
Administration
Alemtuzumab:
- See the Product Monograph for full details of preparation and administration.
- Full resuscitation facilities and experienced personnel should be available.
- Do not administer as an intravenous push or bolus.
- Mix in 100mL IV bag (5% Dextrose or Normal Saline). Gently invert the bag to mix the solution. Infuse the admixture over 2 hours.
- Other drug substances should not be added or simultaneously infused through the same intravenous line.
- Infusion reactions with subcutaneous alemtuzumab are much milder (off-label route of administration) than IV. Consider subcutaneous administration (except in patients with T-PLL).
Rituximab IV:
- Rituximab infusions should be administered in a setting where full resuscitation facilities are immediately available, and under the close supervision of someone experienced and capable of dealing with severe infusion-related reactions.
- DO NOT administer as an IV push or bolus.
- Dilute to a final concentration of 1-4 mg/mL in normal saline or D5W.
- To avoid foaming, gently invert the bag to mix the solution.
- Do not admix with other drugs.
- Administer rituximab through a dedicated line.
- Compatible with PVC or polyethylene bags.
- Keep vials refrigerated; do not freeze. Protect from light.
Infusion rates:
- First infusion:
- Recommended to be administered over a graduated rate: Initial rate of 50 mg/h, then escalate rate in 50 mg/h increments every 30 minutes, to a maximum of 400 mg/h (about 4.25 hours in total).
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Subsequent infusions:
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If no severe infusion reaction (grade 3 or 4) occurred with the first cycle, a rapid infusion of IV rituximab over a total of 90 minutes can be initiated with cycle 2 (20% of the dose in the first 30 min then the remaining 80% over 60 min).
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OR initial rate of 100 mg/h, then escalate rate in 100 mg/h increments every 30 minutes, to a maximum of 400 mg/h as tolerated (about 3.25 hours in total).
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Alternatively, subcutaneous administration of rituximab can be considered starting with cycle 2.
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When bulky disease present or WBC > 25-50 x 109/L, consider:
- A slower infusion rate, or
- Split dosing over days 1-2, or
- Delaying rituximab treatment until chemotherapy has reduced the lymphocyte count
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Contraindications
- Patients with known hypersensitivity and anaphylactic reactions to rituximab, proteins of similar mouse or human origin, to Chinese Hamster Ovary (CHO) cell proteins or to alemtuzumab or any components of MabCampath
- Patients who have or have had PML, have active and/or severe infections, active hepatitis B, or severely immunocompromised (e.g. AIDS patients with very low CD4 or CD8 counts), or active secondary malignancies
- Avoid the use of live vaccines.
Other warnings/precautions:
- Gradual dose escalation of alemtuzumab to the recommended maintenance dose is required at the initiation of therapy and after interruption of therapy for more than 7 days. Alemtuzumab can result in serious and even fatal infusion reactions.
- Single doses of alemtuzumab greater than 30mg or cumulative doses of more than 90mg per week should not be administered, as they are associated with a higher incidence of pancytopenia.
- Exercise caution in patients with a history of recurring or chronic infections or with underlying conditions which may further predispose patients to serious infection.
- Anti-viral and anti-Pneumocystis carinii pneumonia prophylaxis are strongly recommended.
- Prior to starting rituximab in HBV seropositive patients, consultation with a liver disease expert is recommended to determine ongoing monitoring of HBV reactivation and its management.
- Exercise caution in patients with neutrophil counts < 1.5 x 109/L and/or platelets < 75 x 109/L due to limited experience in this patient group.
- Use with extreme caution in patients with pre-existing cardiovascular disease or in patients with high tumour burden.
- Consider steroids ± slow infusions or infusions split over 2 days for patients with bulky disease or > 25 x 109/L circulating malignant cells.
- Use with caution in patients with pulmonary insufficiency or lung tumour infiltration
Pregnancy/lactation
- This regimen is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners while on treatment and after the last treatment dose. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information.
- Breastfeeding is not recommended during this treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
Recommended Clinical Monitoring
- CBC; baseline and before each treatment
- Liver and renal function tests; baseline and before each treatment
- CD4+ counts should be assessed after treatment until recovery to ≥ 200 cells/microL
- Clinical assessment of infusion-related reactions / hypersensitivity, tumour lysis syndrome, hypotension, infection, bleeding, GI, pulmonary, skin, CNS, cardiovascular side effects; at each visit
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
- Monitor closely for cardiovascular symptoms for patients who have cardiac conditions
- Consider CMV monitoring
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Alemtuzumab, rituximab drug monographs, Cancer Care Ontario.
Brown JR, Messmer B, Werner L, et al. A phase I study of escalated dose subcutaneous alemtuzumab given weekly with rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma. Hematologica. 2013; 98(6): 964-970.
Faderl S, Ferrajoli A, Wierda W, et al. Alemtuzumab by continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of patients with chronic lymphocytic leukemia recurrence. Cancer. 2010 May 15;116(10):2360-5.
Faderl S, Thomas DA, O’Brien S, et al. Experience with alemtuzumab plus rituximab in patients with relapsed and refractory lymphoid malignancies. Blood. 2003;101:3413-3415.
Lundin J, Kimby E, Bjorkholm M, et al. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood 2002;100(3):768-773.
Zent CS, Call TG, Shanafelt TD, et al. Early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab. Cancer. 2008 Oct
15;113(8):2110-8.
November 2023 Modified Pregnancy/breastfeeding section
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.
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Regimen Monographs
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