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Treatment Name: C10403 Interim Maintenance

C10403 Interim Maintenance is a Chemotherapy Regimen for Acute Lymphoid Leukemia (ALL)

What is C10403?

C10403 is an aggressive and complex treatment regimen for adolescents and young adults (AYA) with ALL. The C10403 regimen is similar to treatment regimens given to pediatric patients (less than 18 y.o.) and are typically more aggressive than regimens given to adults (40 years or older).

The entire C10403 chemotherapy regimen consists of 5 different treatment courses: induction, consolidation, interim maintenance (this page), delayed intensification, and maintenance.

C10403 interim maintenance (Course III) typically begins shortly after completion of the consolidation phase, unless white blood cell count or platelets are too low.

The interim maintenance phase (Course III) of C10403 consists of the following three medications:

  • Vincristine (Oncovin®)
  • Methotrexate
  • Pegaspargase (Oncaspar®)

How does C10403 therapy work?

Each of the medications in C10403 are designed to target and kill acute lymphoblastic leukemia cells in the blood, bone marrow, or wherever else they may happen to be.

Goals of C10403 interim maintenance (Course III) therapy:

C10403 interim maintenance (Course III) is given to eliminate any remaining leukemia cells and maintain remission from the leukemia. The C10403 protocol is commonly given with the goal of cure.

Schedule

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How is interim maintenance therapy for ALL given?

  • Methotrexate intravenous (I.V.) push on Days 1, 11, 21, 31, and 41
  • Vincristine I.V. push or I.V. infusion over 10 to 15 minutes on Days 1, 11, 21, 31, and 41
  • Pegaspargase I.V. infusion over 1 to 2 hours or intramuscular (I.M.) injection on Days 2 and 22
    • Pre-medications, including diphenhydramine (Benadryl®), hydrocortisone, and acetaminophen (Tylenol®) may help to reduxce the risk of significant hypersensitivity or allergic reaction from pegaspargase (Oncaspar®)
    • If anaphylaxis occurs from PEGaspargase, your doctor may switch you to another type of asparaginase known as Erwinia asparaginase
  • Methotrexate intrathecal (I.T.) injection on Days 1 and 31

If your white blood cells or platelets are too low on treatment day, your dose of methotrexate and vincristine may need to be delayed and you will have your blood counts rechecked, likely in 4 days. If your blood counts recover to acceptable levels, your dose of methotrexate and vincristine may then be given. If your blood counts do not recover to acceptable levels, vincristine only may be given and the dose of methotrexate may need to be skipped or delayed. Your white blood cell and platelet counts do not affect the decision to administer pegaspargase therapy.

Estimated total infusion time for C10403 Interim Maintenance:

  • Up to 2 hours for days when methotrexate and vincristine are both given. Up to 2 hours on days when pegaspargase is given
  • Infusion times are based on clinical studies, but may vary depending on doctor preference, patient tolerability, and drug availability. Pre-medications and intravenous (I.V.) fluids, such as hydration, may add more time
  • Intrathecal chemotherapy administration may also add 1 to 3 hours to the time spent in the clinic or hospital on the days that it is given

C10403 interim maintenance is usually given in an outpatient infusion center, allowing the person to go home after each planned treatment. On occasion, C10403 interim maintenance may be given in the hospital if close monitoring is needed.

Click here for the common C10403 Interim Maintenance starting doses

Side Effects

What are the most common side effects from C10403 interim maintenance for ALL?

In a multi-drug regimen, each medication has unique side effects. When these medicines are given together, drug-related side effects reported in clinical studies give the best estimate of what to expect. In clinical studies, the most commonly reported serious (grade 3 or 4) side effects of C10403 interim maintenance (Course III) are shown here:

  • Neutropenic fever (44%)
  • Infection (26%)
  • Numbness or tingling in fingers or toes (15%)
  • Increased blood triglycerides (12%, may require treatment)
  • Fatigue (12%)
  • Increased blood sugar (11%)
  • Allergic reaction (11%)
  • Blood clot (9%)
  • Mouth sores (9%)
  • Inflammation of the pancreas, or pancreatitis (4%)
  • Difficulty with using hands or feet, such as buttoning a short or walking up stairs (4%)

On average, 2% of patients discontinue interim maintenance (Course III) due to unacceptable side effects.

Watch videos on common C10403 interim maintenance therapy side effects below

Side effect videos Side Effect Videos
Neutropenic FeverNeutropenic FeverFatigue Fatigue Blood ClotsBlood ClotsAnemiaAnemiaNausea and VomitingNausea and VomitingDiarrheaDiarrheaBleedingBleeding

Monitoring

How often is monitoring needed?

Labs (blood tests) may be checked before treatment and periodically in-between treatments if needed. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, amylase, lipase, triglycerides, plus any others your doctor may order.

How often is imaging needed?

Imaging may be checked before treatment and during treatment if there is a concern for infection or medication side effect. Imaging may include: X-rays, magnetic resonance imaging (MRI), or computerized tomography (CT) scans.

How might blood test results/imaging affect treatment?

Depending upon the results, your doctor may advise to continue C10403 interim maintenance (Course III) as planned, or delay or switch therapy, or adjust doses of certain medications for tolerability.

ChemoExperts Tips

What are the 9 most important things to know about C10403 interim maintenance when receiving treatment?

  • Leucovorin is a form of folic acid used to rescue either cells, or prevent damage from methotrexate when larger dose of methotrexate are given. Leucovorin is typically given until blood levels of methotrexate decrease to an acceptable level
  • An antiviral medication such as acyclovir or valacyclovir (Valtrex®) is usually prescribed to prevent viral infections and taken throughout therapy, including the maintenance phase
  • A medicine known as sulfamethoxazole/trimethoprim (more commonly called Bactrim®), is prescribed to prevent a specific type of pneumonia known as pneumocystis jiroveci pneumonia (PJP pneumonia). Because Bactrim can interact with certain medications such as methotrexate, your doctor, nurse, or pharmacist will tell you to hold certain doses to prevent potentially severe side effects from methotrexate
  • Premedications such as acetaminophen (Tylenol®) and diphenhydramine (Benadryl®) are typically given prior to pegaspargase (Oncaspar®) to help prevent infusion reactions. With pre-medications, severe reactions develop in roughly 6% of patients receiving pegaspargase (Oncaspar®), without pre-medications reactions may be as high as 15%. If severe allergic reactions develop, an alternate form of pegaspargase (known as Erwinia, or Erwinaze®) may be given instead
  • If pegaspargase is given by intramuscular (I.M.) injection, multiple injections may have to be given as only a certain volume of pegaspargase can be injected at once
  • Omeprazole (Prilosec®) or a similar medication may be given to prevent stomach ulcers, however it is best not to take omeprazole on the days that methotrexate is given as it could make the methotrexate more toxic
  • Clinical outcomes may be improved by seeking treatment from a University Hospital or National Cancer Institute (NCI)-sponsored cancer center where there may be more experts with experience in treating patients with acute lymphoblastic leukemia
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • Clinical trials may exist for ALL. Ask your doctor if any studies are currently enrolling in your area. If not, go to clinicaltrials.gov to search for other centers offering study medications.

Patient Assistance & Co-payment Coverage

Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for C10403 Interim Maintenance, we have provided links that may help.

Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for C10403 Interim Maintenance. Depending upon your income, they may be able to help cover the cost of:

  • Vincristine
  • Methotrexate
  • Pegaspar­gase

For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.

  • If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.

Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as C10403 Interim Maintenance and are the best source to help you understand drug cost.

  • Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.

Emotional Wellness

What is Emotional Wellness?
Emotional wellness is having a positive outlook balanced with a realistic understanding of current life events. This requires both an awareness and acceptance of your emotions. It is with this knowledge that you can develop a plan to take the necessary actions to positively impact your life.

Emotional wellness uses an ongoing process to continually reflect on the stressors of life in a constructive manner to move forward and create happiness.

Because emotional wellness is deeply connected with physical, social, and spiritual wellness, pursuing it often becomes particularly difficult in times of major illness. Despite this difficulty, working toward emotional wellness has been connected to improved treatment outcomes and a higher likelihood of achieving goals of therapy.

Learn more about pursuing emotional wellness while receiving treatment with C10403 Interim Maintenance

Individual Drug Label Information

Vincristine (Oncovin®)

  • ​Vincristine MUST only be given by intravenous infusion. May NOT be administered any other way
  • Dosage may be reduced in patients with poor liver function
  • May interact with certain antifungal medications
  • Vincristine will cause death if administered into spinal fluid
General Vincristine (Oncovin) Side Effects
  • Nerve pain in hands or feet may increase after each dose. It is usually reversible if treatment is stopped or dose is adjusted
  • Hair loss is NOT common if vincristine is given by itself
  • May cause constipation; preventative medicines may help decrease or avoid constipation
  • Leakage into skin or surrounding muscle may cause severe irritation (extravasation)
  • Click on the vincristine (Oncovin) package insert below for reported side effects and potential drug interactions

Side Effect Videos
ConstipationConstipationPainPain

See DailyMed package insert.

Methotrexate (Trexall®)

  • Methotrexate is an intravenous infusion and is bright yellow in color 
  • Methotrexate has the following FDA Black-Box Warnings. The risk of experiencing these side effects is much higher if methotrexate is not cleared from the body appropriately:  
    1. Low red blood cells, white blood cells, and platelets
    2. Kidney injury
    3. Liver injury
    4. Severe diarrhea
    5. Mouth ulcers
    6. Stomach ulcers
  • Dosage adjustments may be required for poor kidney function or poor liver function 
  • May cause severe skin reactions a few days after administration 
  • Is harmful to the fetus during pregnancy. If you are of childbearing age, use multiple forms of birth control 
  • May interact with non-steroidal inflammatory drugs (NSAIDs), aspirin, proton-pump inhibitors, phenytoin, and sulfa or penicillin antibiotics. These drugs should NOT be used the day before or the day of therapy with methotrexate. 
  • Ask your doctor or pharmacist to review your medications prior to receiving methotrexate 
  • Click on the methotrexate package insert below for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaHair LossHair LossFatigue Fatigue PainPainAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Pegaspar­gase (Oncaspar®)

  • Is an intravenous infusion or intramuscular injection
  • Dosage adjustments may be required for liver function or side effects
General side effects from pegaspargase (Oncaspar®)
  • May cause infusion reactions. Premedications may be given prior to pegasparaginase to help prevent infusion reactions
  • Can cause problems with the body’s clotting system causing it to clot too much or not enough and cause bleeding. Contact your doctor if you notice any unusual bruising or bleeding, unexplained pain in your legs or arms, chest pain, or severe shortness of breath
  • Severe liver injury can occur. Some signs of serious liver injury can be yellowing of skin or eyes, abdominal pain or dark colored urine
  • May cause inflammation of the pancreas (pancreatitis). Contact your doctor if you experience any unexplained severe abdominal pain
  • May cause an increase in blood sugar. If you have diabetes, you may need to adjust the doses of your insulin or hypoglycemic medications
  • Click on the pegasparaginase (Oncaspar®) package insert below for reported side effects and possible drug interactions

Side Effect Videos
BleedingBleedingPainPainBlood ClotsBlood Clots

See DailyMed package insert.

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References

1) Curran E and Stock W. How I treat acute lymphoblastic leukemia in older adolescents and young adults. Blood 2015;125:3702-3710.

2) Stock W, Luger SM, Advani AS, et al. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403. Blood. 2019;133:1548-1559.

Created: December 6, 2019 Updated: December 6, 2019

What is Acute Lymphoid Leukemia (ALL)?

Acute Lymphoid Leukemia (ALL), also known as acute lymphoblastic leukemia, is a disease of the lymphoid cells found in the bone marrow. Lymphoid cells are responsible for developing into cells of the immune system called B-cells, T-cells, or Natural Killer cells. In ALL, immature lymphoid cells know as "blasts" replicate at a very fast rate. Sometimes blasts crowd out the normal cells in the bone marrow so that red blood cells or platelets are unable to develop.

Common symptoms of ALL include fatigue, infection, and bruising or bleeding. ALL is the most common cancer diagnosed in children, but is rare in adults. Most cases of ALL are considered "de novo" meaning that the cause is unknown; however, some cases can be linked to certain genetic syndromes. There is no staging system for ALL. Chromosomes are often analyzed to determine which mutations in the chromosomes exist. The effectiveness of the treatment may depend upon the specific chromosome mutations that are present.

NOTE: Treatment Options listed below are not all-inclusive. Other treatments may be available. ChemoExperts provides drug information and does not recommend any one treatment over another. Only your Doctor can choose your therapy.

Common C10403 Interim Maintenance starting doses

  • Methotrexate 100 mg/m2 intravenous (I.V.) push on Day 1
    • Then Methotrexate 150 mg/m2 I.V. push on Day 11
    • Then Methotrexate 200 mg/m2 I.V. push on Day 21
    • Then Methotrexate 250 mg/m2 I.V. push on Day 31
    • Then Methotrexate 300 mg/m2 I.V. push on Day 41
  • If ANC > 750/μL and platelets > 75,000/μL, escalate methotrexate by 50 mg/m2 per dose as scheduled
  • If ANC ≥ 500/μL but ≤ 750/μL and/or platelets ≥ 50,000/μL but ≤ 75,000/μL, give same dose of methotrexate as given previously (no dose escalation)
  • If ANC < 500/μL or platelets < 50,000/μL, hold all chemotherapy and repeat blood counts in 4 days
    • If ANC recovers to ≥ 500/μL and platelets to ≥ 50,000/μL, give the same dose of methotrexate as given previously
    • If ANC is still < 500/μL or platelets still < 50,000/μL, give vincristine only and repeat counts in 7 days to begin next dose of methotrexate if counts are adequate. Do not make up missed dose of methotrexate.
  • If ANC < 750/μL or platelets < 75,000/μL for more than 7 days after methotrexate, then discontinue Bactrim temporarily. If toxicity for more than 7 days recurs after the next dose, once ANC > 750/μL and platelets > 75,000/μL, then methotrexate should be given at 75% of the previous dose. If neutropenia does not recur after 2 doses of methotrexate at a reduced dose, increase methotrexate to the previous higher dose.
  • Vincristine 1.5 mg/m2 (maximum 2 mg) I.V. push or I.V. infusion over 10 to 15 minutes on Days 1, 11, 21, 31, and 41
  • Pegaspargase 2500 IU/m2 (maximum 3750 IU) I.V. infusion over 1 to 2 hours or intramuscular (I.M.) injection on Days 2 and 22
  • Methotrexate 15 mg intrathecal (I.T.) injection on Days 1 and 31

What are adolescents and young adults (AYAs)?

The age range for this population is generally considered to be those between 18 - 39 years old, although this age range may vary slightly.

What does Cure mean?

The word “cure” means there are no cancer cells left in the body and cancer will never come back. Depending on the cancer type and stage, this may be the true goal of therapy. However, it is very difficult to prove all cancer cells are gone. Even though images, like X-rays and MRI’s, and blood tests may not show any signs of cancer, there can be a small amount of cancer cells still left in the body. Because of this, the word “remission” is used more often. This means there are no signs or symptoms of cancer. Patients in remission are followed closely for any signs of cancer returning. Sometimes, more chemotherapy may be given while in remission to prevent the cancer from coming back.

Doctors usually do not consider a patient “cured” until the chance of cancer returning is extremely low. If cancer does return, it usually happens within 5 years of having a remission. Because of this, doctors do not consider a patient cured unless the cancer has not come back within 5 years of remission. The five-year cutoff does not apply to all cancers.

What is a CBC?

A Complete Blood Count (CBC) is a frequently ordered blood test that tells clinicians the status of your: 1) White blood cell count, 2) Hemoglobin, and 3) Platelet count at the time the test was taken.

Common uses:
1) White blood cell count (WBC): is used to determine infection risk, or response to chemotherapy. Certain chemotherapy agents may harm our good infection-fighting cells. Sometimes chemotherapy may need to be delayed to allow these cells to recover.

2) Hemoglobin: is used to determine if someone is anemic. Anytime the hemoglobin is below 12 g/dL, the person is said to be anemic. Red blood cell transfusions, and sometimes iron can be given to restore the hemoglobin level, but anemia treatment should always aim at treating the underlying cause or condition.

3) Platelet count: is used to determine if the risk of bleeding is increased or if a platelet transfusion is required to prevent bleeding. Certain medications that increase bleeding risk, such as: aspirin, certain chemotherapy agents, and blood thinners, may need to be stopped temporarily until the platelet count is within a safe range.

What is a CMP?

A Comprehensive Metabolic Panel (CMP) is a frequently ordered blood test that tells clinicians the status of your: 1) Electrolytes & Acid/Base status2) Kidney function, 3) Liver function, 4) Blood sugar, and 5) Calcium at the time the test was taken. It is commonly used to monitor liver and kidney function when beginning new medications such as chemotherapy. A total of 14 tests are run simultaneously and are shown below.

Electrolytes & Acid/Base status:
1) Sodium, 2) Potassium, 3) Carbon dioxide, 4) Chloride

Kidney Function:
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)

Liver Function:
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein

Blood sugar:
13) Serum glucose

Calcium:
14) Serum calcium

What is Fibrinogen?

Fibrinogen is a clotting factor that gets converted to fibrin and plays a role in the final steps of clot formation. Fibrinogen may be supplemented during treatment in the form of cryoprecipitate, a human-derived product, that is transfused by I.V. infusion to increase fibrinogen levels and decrease the risk of bleeding.

What is amylase?

Amylase is an enzyme that is produced by the pancreas that helps the body break down and digest carbohydrates. When the pancreas is injured, amylase is leaked out into the blood. 

Amylase, along with lipase, can be monitored to check for possible injury to the pancreas, indicated by elevated levels of the enzymes in the blood.

What is Lipase?

Lipase is an enzyme that is produced by the pancreas that helps the body break down fats. When the pancreas is injured, lipase is leaked out into the blood. Lipase, along with amylase, can be monitored to check for possible injury to the pancreas, indicated by elevated levels of the enzymes in the blood.