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HYPERCVAD+RITU

Cancer Type: Hematologic, Lymphoma - Non-Hodgkin's Low Grade  Intent: Palliative
Regimen Category: Evidence-informed
Funding:
New Drug Funding Program
    Rituximab in Combination with Chemotherapy - Indolent B-cell Lymphoma
New Drug Funding Program
    Rituximab (SC) in Combination with Chemotherapy - Indolent B-cell Lymphoma
ODB - General Benefit
    dexamethasone
A - Regimen Name

HYPERCVAD+RITU Regimen
Cyclophosphamide-Vincristine-Doxorubicin-Dexamethasone-Methotrexate-Leucovorin-Cytarabine-riTUXimab


Disease Site
Hematologic - Lymphoma - Non-Hodgkin's Low Grade

Mantle cell lymphoma


Intent
Palliative

Regimen Category
Evidence-informed :

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.

This 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). 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.


Rationale and Uses

For previously untreated patients with aggressive mantle cell lymphoma​.


Supplementary Public Funding

riTUXimab
New Drug Funding Program (Rituximab in Combination with Chemotherapy - Indolent B-cell Lymphoma) (NDFP Website)

riTUXimab (subcut)
New Drug Funding Program (Rituximab (SC) in Combination with Chemotherapy - Indolent B-cell Lymphoma)

dexamethasone
ODB - General Benefit (dexamethasone)

 
B - Drug Regimen

This regimen consists of 8 alternating courses of Course A (cyclophosphamide, vincristine, doxorubicin, dexamethasone and rituximab) and Course B (methotrexate, cytarabine and rituximab), given every 21 to 28 days (A-B-A-B-A-B-A-B).  

The following includes regimen details for Course A, adapted for outpatient administration.

Cycle 1 of Course A (Cycle 1 of HYPERCVAD):

All patients must receive thier first dose of rituximab by IV infusion.

riTUXimab
375 mg /m² IV Day 1

 

Plus HYPERCVAD Chemotherapy:
 

cyclophosphamide

600 mg /m² IV (max 1320 mg) Days 1 to 3
DOXOrubicin
50 mg /m² IV Day 4*
vinCRIStine
1.4 mg /m² IV (max 2 mg) Days 4* and 11
dexamethasone
40 mg PO Days 1, 2, 3, 4, 11, 12, 13, 14


Subsequent cycles of Course A (Cycles 3, 5, 7 of HYPERCVAD):

Rituximab IV

riTUXimab
375 mg /m² IV Day 1


OR

Rituximab subcutaneous:
The subcutaneous formulation must only be given at the second or subsequent cycles, if the patient has previously received at least one full rituximab IV dose.

riTUXimab (subcut)
1400 mg Subcut Day 1


Plus HYPERCVAD Chemotherapy:

cyclophosphamide

600 mg /m² IV (max 1320 mg) Days 1 to 3
DOXOrubicin
50 mg /m² IV Day 4*
vinCRIStine
1.4 mg /m² IV (max 2 mg) Days 4* and 11
dexamethasone
40 mg PO Days 1, 2, 3, 4, 11, 12, 13, 14

some centres have given cyclophosphamide as 300 mg/m2 IV q12h on Days 1 to 3.  Consider mesna, as per local protocols.
*some centres may administer on day 3

For Course B (inpatient), refer to local protocols.

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C - Cycle Frequency

REPEAT EVERY 21 TO 28 DAYS (alternating with Course B) for a usual total of 8 cycles unless disease progression or unacceptable toxicity

 
J - Administrative Information

Pharmacy Workload (average time per visit)
21.697 minutes
Nursing Workload (average time per visit)
53.125 minutes
 
K - References

Bernstein SH, Epner E, Unger JM, et al.  A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213.   Ann Oncol 2013;24(6):1587-93.

Davies A, Merli F, Mihaljević B, et al.  Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial.  Lancet Haematol. 2017 Jun;4(6):e272-e282.

Merli F, Luminari S, Ilariucci F, et al. Rituximab plus HyperCVAD alternating with high dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma, a multicentre trial from Gruppo Italiano Studio Linfomi. Br J Haematol 2012;156(3):346-53.

Romaguera JE, Fayad L, Rodriguez MA, et al. High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol. 2005 Oct 1;23(28):7013-23.

Romaguera JE, Fayad LE, Feng L, et al. Ten-year follow-up after intense chemoimmunotherapy with Rituximab-HyperCVAD alternating with Rituximab-high dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma. Br J Haematol 2010;150(2):200-8.


PEBC Advice Documents or Guidelines

July 2018 Added rituximab subcutaneous option and corresponding NDFP forms


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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.
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