3725-Burkitt lymphoma R-IVAC (rituximab iFOSFamide etoposide cytarabine) (2024)

Table of Contents
Efficacy Toxicity FAQs

The dose modified (dm)CODOX-M / IVAC protocol for Burkitt Lymphoma (BL) is an iteration of the original treatment regimen described by Magrath et al. in 1996.r The intention was to provide a dose-intensive, compact, non-cross-resistant regimen with effective central nervous system (CNS) targeting. The promising results of this study were confirmed in the LY06 study, a larger, multicentre, international phase 2 trial.rThis regimen was refined in the LY10 trial, wheremethotrexate was dose modifiedto 3 g/m2 (from 6.7 g/m2)to reduce toxicity.r LY10 forms the basis of the current eviQ protocol.

LY10 was a prospective, international, non-­randomised phase 2 study that included 53 patients (median age 37 years; range 17 to 76 years) with newly diagnosed BL. Patients with documented CNS involvement received additional intrathecal therapy. The LY10 trial included 11 low-risk and 42 high-risk patients.Patients were considered 'Low Risk' if they had at least 3 of the 4 following international prognostic index (IPI) factors: normal LDH, Ann Arbor stage I to II, WHO performance status 0 to 1 and number of extranodal sites less than or equal to 1. These patients were treated with three cycles of dm CODOX-M.All other patients were considered 'High Risk' and received alternating cycles of dm CODOX-M / IVAC twice. Two­ year progression-free survival (PFS) and overall survival (OS) rates were 64% and 67%, respectively.r

In recent years, it has been common practice to add rituximab to the dm CODOX-M / IVAC regimen, as its use in combination with standard chemotherapy has demonstrated improved patient outcomes without additional toxicity in several prospective studies.

A French phase 3 multicenter, open-label trial of 260 patients with newly-diagnosed BL, randomised patients to receive dose-dense chemotherapy with or without additional rituximab.rAfter a median follow-up of 38 months, patients receiving rituximab had a superior three year event-free survival (EFS) (hazard ratio [HR], 0.59; 95% CI, 0.38-0.94; P=.025) and OS (HR, 0.51; 95% CI, 0.30-0.86; P=.012) compared with the no-rituximab group.rAdverse events and toxicity were comparable across the two groups across each risk category. A phase 2 prospective multicentertrial for adult BL patients examined the efficacy and tolerability of rituximab in addition to dose-dense chemotherapy in 363 patients across 98 European centres.rRituximab was given before each cycle, with two additional maintenance doses, for a total of 8 doses. Five year PFSand OS rates were 71% and 80%, respectivelywith a complete remission (CR) rate of 88%.

The largest prospective study (n=27) specifically evaluatingdm R-CODOX-M / R-IVAC in BL utilised rituximab (375 mg/m2) on day 1 of eachcycle, with additional doses on day 11 of CODOX-M and on days 21 and 42 after the final IVAC cycle.rAfter a median follow-up of 56.9 months (range 2.2-77.5), 2-year PFS was 77.2% and 2-year OSwas 80.7%. Six deaths occurred in total, due to progressive lymphoma (n = 3), treatment-effect (n = 2) or salvage chemotherapy (n = 1). Overall, this regimen was associated with acceptable toxicity and outcomes commensurate with historical dm CODOX-M / IVAC patients who were not exposed to rituximab. Comparable results were seen in another prospective study which added rituximab 375 mg/m2 on day 1 of each dm CODOX-M and IVAC cycle.r15 patients with BL were evaluated with four-year PFS of 92% and OS of 82%.

Another prospective study incorporated high-dose rituximab (500 mg/m2) twice a cycle in addition to the dm CODOX-M / IVAC regimen in 25 newly diagnosed BL patients.rTwo-year PFS and OS rates of 80% and 84%, respectively across all risk categories, and toxicity profile was comparable to prior reports.

Several other groups have reported retrospective data on CODOX-M / IVAC based regimens combined with rituximab.rrrrA recent Canadian study examined survival outcomes of 81 patients with BL treated with dm CODOX-M / IVAC combined with rituximab 375 mg/m2 (added on day 8 of each dm CODOX-M and day 4 of each IVAC cycle).They obtained a five year PFS and OS of 75% and 77%, respectively, with no treatment-related deaths. Treatment modifications due to toxicity were common in this cohort, however those who completed the regimen per protocol (n = 38) had significantly improved PFS 86% (P = 0.04) and OS 92% (P = 0.012).r

SourceStudy & Year PublishedSupports UseIs the dose and regimen consistent with theprotocol?Comments
Phase III trialsRibraget al.rYesNo

Alternate chemotherapy backbone

Mead et al. (LY06 trial)rYesNo

Higher methotrexate dose of 6.7 g/m2

Mead et al. (LY10 trial)rYesNo

Rituximab not included in the treatment regimen

Chemotherapy backbone identical

Hoelzer et al.rYesNo

Alternate chemotherapy backbone

Phase II trialsMcMillan et al.rYesNo

Rituximab 375 mg/m2 concurrently on day 1 of each cycle, with additional doses on day 11 of CODOX-M and days 21 and 42 after the final IVAC cycle (8 doses of rituximab in total)

Corazzelli et al.rYesNo

Higher doxorubicin dose of 50 mg/m2

Evens et al.rYesNo

Higher rituximab dose of 500 mg/m2

Zhu et al.rYesYes

Rituximab administered on day 8 ofdm CODOX-M and day 4 of IVAC, for each cycle

GuidelinesDate published / revisedSupports UseIs the dose and regimen consistent with theprotocol?Comments
NCCNv.5 2021YesYes-
BCCAMay 2021YesYes

Doses and scheduling of some drugs are different, but overall regimen is the same

CCOAugust 2020YesYes

High-dose methotrexate (day 10) and leucovorin (start day 11) are given as inpatient

Efficacy

Progression-free survival and overall survival in the LY10randLY06r and studies, with risk group defined as in LY10:

3725-Burkitt lymphoma R-IVAC (rituximab iFOSFamide etoposide cytarabine) (1)

© Blood 2008

Toxicity

In the LY10 study,r there were 9 deaths (1 low-risk, 8 high-risk) reported to be treatment-related, of which 5 (all high-risk patients) died within 12 weeks of starting treatment; 2 of the 9 patients were aged over 65 (66 and 67, respectively).

3725-Burkitt lymphoma R-IVAC (rituximab iFOSFamide etoposide cytarabine) (2)

© Blood 2008

3725-Burkitt lymphoma R-IVAC (rituximab iFOSFamide etoposide cytarabine) (2024)

FAQs

What is IVAC chemotherapy? ›

What is IVAC? IVAC is a combination of different chemotherapy drugs: ifosfamide. etoposide. cytarabine.

What drugs are in Codox M Ivac? ›

R-CODOX-M
DrugDoseRoute
Cytarabine70 mgIntrathecal
Methotrexate12 mgIntrathecal
Calcium folinate (leucovorin)15 mgPO

Is Codox M IVAC effective? ›

R-CODOX-M/R-IVAC is an effective regimen for treatment of high-risk DLBCL and high-grade B-cell lymphoma (IPI score 3–5). Treatment was well tolerated in patients aged <50 years, or aged 50–65 with performance status 0 or 1. The 2-year PFS was 67.9% (90% CI: 59.9–74.6) for the whole cohort.

Is Burkitt's lymphoma sensitive to chemotherapy? ›

Historically recognized as a model for research advances regarding pathogenesis, cytogenetics and molecular genetics, as well as the first intensely chemo-sensitive tumor to be described, Burkitt Lymphoma/leukemia (BLL) was initially described as a tumor affecting the jaws of African children,1 and is nowadays ...

Can you recover from Burkitt lymphoma? ›

Most children who have treatment for Burkitt lymphoma are cured. The outcome is also very good for younger adults. In older adults, Burkitt lymphoma can be more difficult to treat because older people are generally less able to tolerate intensive treatments.

What is the survival rate for Burkitt's lymphoma stage 3? ›

Treatment of limited stage (stage I and II) Burkitt lymphomas is usually very successful, with a long-term survival rate of over 90%. The long-term survival rate for children and teens with more advanced (stage III or IV) Burkitt lymphoma ranges from about 80% to 90%.

What are the benefits of taking Codox? ›

Codox 100mg Capsule is an antibiotic medicine used to treat bacterial infections in your body. It is effective in some infections of the lungs, urinary tract, eyes, and others. It kills bacteria, which helps to improve your symptoms and cure the infection. It may also be used for the treatment of severe acne.

What type of drug is rituximab? ›

Rituximab injection is a monoclonal antibody. Rituximab injection is used together with other medicines (eg, fludarabine cyclophosphamide) to treat chronic lymphocytic leukemia (CLL). Rituximab injection is used together with methotrexate to treat the symptoms of rheumatoid arthritis.

What are the side effects of taking Codox L? ›

Major & minor side effects for Codox-L Capsule
  • Stomach pain.
  • Headache.
  • Joint pain.
  • Blurred vision.
  • Difficult or painful urination.
  • Dry mouth.
  • Loss of appetite.
  • Nausea or Vomiting.
Dec 6, 2021

What is stage 4 Burkitt's lymphoma? ›

Stages of Burkitt lymphoma

The stages range from Stage 1 to Stage 4. In Stage 1 the lymphoma cells are in one area of your body (usually the lymph nodes), in Stage 4 they have spread to the bone marrow and/or your brain and spinal cord.

How bad is Burkitt's lymphoma? ›

The cancer is also linked to other diseases, including Epstein Barr virus (EBV), human immunodeficiency virus (HIV), and certain chromosomal abnormalities. Though it's considered an aggressive form of cancer, Burkitt lymphoma is usually treatable.

What is the first indication of Burkitt lymphoma? ›

The symptoms of Burkitt lymphoma depend on the type. The endemic (African) variant usually starts as tumors of the jaw or other facial bones. It also can affect the gastrointestinal tract, ovaries, and breasts and can spread to the central nervous system, causing nerve damage, weakness, and paralysis.

What does IVAC do? ›

IVAC offers financial assistance to victims

medication. childcare. psychotherapy or psychosocial follow-up. moving expenses.

How does IVAC work? ›

Plug a power bar into the Tool Power outlet of the Switch Box and plug your tools into the power bar. Any tool will now trigger the Switch Box to turn on the vacuum. Remember though that the maximum current you can draw from the Tool Power outlet is 15 amps so you may not be able to run more than one tool at a time.

What does the IVAC stand for? ›

The International Vaccine Access Center (IVAC) was created out of the PneumoADIP (Pneumococcal Accelerated Development and Introduction Plan), a major Gavi-supported project that began work at the Johns Hopkins Bloomberg School of Public Health in 2003, and the Hib Initiative, a Gavi-supported project that began at the ...

What does IVAC stand for in medical? ›

before an event can meet Infection-related Ventilator-Associated complication (IVAC) and IVAC criteria must be met before identifying a Possible Ventilator-Associated Pneumonia (PVAP) event.

Top Articles
Latest Posts
Recommended Articles
Article information

Author: Fr. Dewey Fisher

Last Updated:

Views: 6269

Rating: 4.1 / 5 (42 voted)

Reviews: 89% of readers found this page helpful

Author information

Name: Fr. Dewey Fisher

Birthday: 1993-03-26

Address: 917 Hyun Views, Rogahnmouth, KY 91013-8827

Phone: +5938540192553

Job: Administration Developer

Hobby: Embroidery, Horseback riding, Juggling, Urban exploration, Skiing, Cycling, Handball

Introduction: My name is Fr. Dewey Fisher, I am a powerful, open, faithful, combative, spotless, faithful, fair person who loves writing and wants to share my knowledge and understanding with you.