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Treatment Name: C10403 Delayed Intensification

C10403 Delayed Intensification 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, delayed intensification (this page), and maintenance.

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

The Delayed Intensification phase (Course IV) of C10403 consists of the following seven medications:

  • Vincristine (Oncovin®)
  • Dexamethasone (Decadron®)
  • Doxorubicin (Adriamycin®)
  • Pegaspargase (Oncaspar®)
  • Cyclophosphamide (Cytoxan®)
  • Cytarabine (Ara-C)
  • Thioguanine (6-TG)

Alternative name: 10403

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

Goals of delayed intensification (Course IV) therapy:
C10403 delayed intensification (Course IV) 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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  • Vincristine intravenous (I.V.) push or I.V. infusion over 10 to 15 minutes on Days 1, 8, 15, 43, and 50
  • Dexamethasone (approximately 2 to 4 tablets) by mouth on Days 1 through 7 and Days 15 through 21
  • Doxorubicin I.V. push or I.V. infusion over 10 to 15 minutes on Days 1, 8, and 15
  • Pegaspargase I.V. infusion over 1 to 2 hours or intramuscular (I.M.) injection on Days 4 (or on Day 5 or Day 6) and 43
    • 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
  • Cyclophosphamide I.V. infusion over 30 to 60 minutes on Day 29
  • Cytarabine I.V. infusion over 1 to 3 hours or subcutaneous (SubQ) injection on Days 29, 30, 31, 32 and Days 36, 37, 38, and 39
  • 6-Thioguanine oral tablets by mouth once daily (at least one hour after evening meal) on Days 29 through 42
    • Different amounts of tablets may need to be taken on certain days of the week. Double check the prescribed daily dose each day before taking 6-thioguanine
  • Methotrexate intrathecal (I.T.) injection on Days 1, 29, and 36

Estimated total infusion time for C10403 Delayed Intensification (Course IV) chemotherapy:

  • Up to 2 hours on days when doxorubicin and cytarabine are both given
  • Up to 3 hours on days when pegaspargase is given
  • Up to 4 hours on days when pegaspargase and vincristine are given
  • Up to 5 hours on days when cyclophosphamide and cytarabine are given
  • Up to 4 hours on days when just cytarabine is given
  • Up to 1 hour on days when just vincristine is given
  • Infusion times are based on clinical studies, but may vary depending on doctor preference or patient tolerability. Pre-medications and intravenous (I.V.) fluids, such as hydration, may add more time
  • Intrathecal chemotherapy administration may also add 1 - 3 hours to the time spent in the clinic or hospital on the days that it is given

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

NOTE: 6-Thioguanine is usually taken at home and must be filled at a retail pharmacy. Not all pharmacies carry this medicine so it is best to call ahead to ensure it is in stock before going there in person.

Click here for the common C10403 delayed intensification starting doses.

Side Effects

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 delayed intensification are shown here:

  • Neutropenic fever (44%)
  • Infection (26%)
  • Numbness or tingling in fingers or toes (15%)
  • Increased blood triglycerides (12%)
  • Fatigue (12%)
  • Increased blood sugar (11%)
  • Allergic reaction (11%)
  • Blood clot (9%)
  • Mouth sores (9%)
  • Inflammation of the pancreas (4%)

On average, 2% of patients discontinue treatment due to unacceptable side effects.

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

Monitoring

How often is monitoring needed with C10403 delayed internsification?
Labs (blood tests) are 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 delayed intensificatgion (Course IV) as planned, or delay or switch therapy, or modify doses to help with tolerability.

ChemoExperts Tips

  • It is usually recommend swallowing 6-thioguanine tablets whole. On occasion, your doctor may have you split them in half. However, the dose of 6-thioguanine per week can often be achieved by alternating the number of tablets you take each day. Your doctor or pharmacist should tell you the exact number of tablets to take on each specific day of the week.
  • 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, even when methotrexate is given intrathecally, your doctor, nurse, or pharmacist will tell 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®) whereas without pre-medications, severe reactions may develop in up to 15% of patients. 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 ulcers from dexamethasone, however it is best not to take omeprazole on the days that methotrexate is given as it could make the methotrexate more toxic
  • Patients may differ in the amount and activity of an enzyme they have that metabolizes 6-thioguanine, called TPMT. In some cases, genetic testing for TPMT may recommended before or during treatment with 6-thioguanine to test for low levels of this enzyme that could lead to increased side effects
  • 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 Delayed Intensification, 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 Delayed Intensification. Depending upon your income, they may be able to help cover the cost of:

  • Vincristine
  • Dexamethasone
  • Pegaspar­gase
  • Cyclo­phospha­mide IV
  • Cytarabine
  • 6-Thioguanine
  • Doxorubicin

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 Delayed Intensification 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 Delayed Intensification

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.

Dexamethasone (Decadron®)

  • Dexamethasone is supplied as an oral tablet or oral liquid
  • Dexamethasone may increase the risk of infection. Depending upon how much dexamethasone is taken, antibiotics may be prescribed to help prevent infection
  • Should be taken with food and with a large glass of water to avoid stomach irritation or ulcers
  • Should be taken before 6 p.m. when possible, to avoid trouble falling asleep
  • May decrease the response to vaccines; vaccines may need to be repeated at a later date to obtain maximal response
  • If taken daily for several days or weeks, the dose of dexamethasone may need to be gradually decreased (tapered) to avoid withdrawal symptoms
  • If you miss a dose, take the next dose as soon as possible
  • Should be stored at room temperature
General Dexamethasone (Decadron) Side Effects
  • May cause high blood sugar, weight gain, irritability, high blood pressure, difficulty sleeping, stomach ulcers, bone loss, muscle weakness
  • Click on the dexamethasone (Decadron) package insert below for reported side effects and potential drug Interactions
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.

Cyclo­phospha­mide IV (Cytoxan®)

  • Cyclophosphamide is administered as an intravenous (I.V.) infusion
  • May decrease the ability to become pregnant. Fertility preservation is recommended in couples wishing to become pregnant.
  • A smaller dosage may be required for patients receiving hemodialysis
  • Has been linked to the development of other cancers in a small number of people
General Cyclophosphamide (Cytoxan) Side Effects
  • Low white blood cell count which can increase the risk of infection
  • Nausea or vomiting, which can be acute (first 24 hours) or delayed (Days 2 – 5)
  • Hair loss, which is usually reversible
  • Click on the cyclophosphamide (Cytoxan) package insert below for reported side effects and potential drug Interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingHair LossHair LossNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Cytarabine (Ara-C)

  • Cytarabine is most commonly given as an intravenous infusion but may be given subcutaneously
  • FDA Black-Box Warnings for low white blood cells, low platelets, low red blood cells, nausea, vomiting, diarrhea, mouth sores, liver damage, and abdominal pain
  • Dosage adjustments may be required renal or liver function
  • May cause a series of symptoms known as Cytarabine (Ara-C) Syndrome within 6 to 12 hours after administration. Symptoms may include fever, rash, chest pain, muscle aches, bone pain, tiredness, and inflammation and redness of the eye
General Cytarabine (Ara-C) Side Effects
  • Low red blood cells, white blood cells, or platelets
  • Nausea or vomiting
  • Liver dysfunction
  • Click on the cytarabine (Ara-C) package insert below for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaFatigue Fatigue BleedingBleedingPainPainAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

6-Thioguanine (6-TG)

  • ​Is an oral tablet available in 40 mg
  • Is usually taken with food in the evening. Tablets should be taken whole but in some cases they may need to be cut in half to achieve the desired dose
  • If you miss a dose, take the next dose at the regularly scheduled time. Do not double the dose to make up for the missed dose
  • Should be stored at 59° to 77°F in a dry place
  • Dosage adjustments may be required for persistently low red blood cells, white blood cells, or platelets
  • May interact with mesalazine, olsalazine, or sulphasalazine causing increased levels of 6-thioguanine in the blood and increase risk of side effects
  • Do not take while pregnant as it may cause fetal harm. Contact your doctor immediately if you become pregnant while taking 6-thioguanine
General side effects from 6-thioguanine
  • Liver damage
  • Low red blood cells, while blood cells, and platelets
  • Nausea/vomiting
  • Weight loss
  • Mouth sores
  • Click on the 6-thioguanine package insert below for reported side effects, possible drug interactions, and other 6-thioguanine prescribing information

Side Effect Videos
Nausea and VomitingNausea and VomitingFatigue Fatigue AnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Doxorubicin (Adriamycin®)

  • Doxorubicin is administered as an intravenous infusion and is red in color
  • Can affect heart function. A heart study (echocardiogram) may be required before receiving the first dose
  • Dosage may be reduced in patients with poor liver function
  • Has been linked to the development of other cancers in a small number of people (1.5% chance at 10 years)
General Doxorubicin (Adriamycin) Side Effects
  • Nausea, vomiting, diarrhea, and mouth sores (stomatitis)
  • Leakage into skin or surrounding muscle during infusion may cause severe irritation (extravasation)
  • May temporarily turn urine orange
  • Hair loss, which is usually reversible
  • Increased risk of infection due to decrease white blood cell count (neutropenia)
  • Click on the doxorubicin (Adriamycin) package insert for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaHair LossHair LossPainPainNeutropenic FeverNeutropenic Fever

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: February 16, 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 delayed intensification starting doses

  • Vincristine 1.5 mg/m2 (maximum 2 mg) intravenous (I.V.) push or I.V. infusion over 10 to 15 minutes on Days 1, 8, 15, 43, and 50
  • Dexamethasone 10 mg/m2 by mouth, divided in two doses per day, on Days 1, 2, 3, 4, 5, 6, 7 and Days 15, 16, 17, 18, 19, 20, 21
  • Doxorubicin 25 mg/m2 I.V. push or I.V. infusion over 10 to 15 minutes on Days 1, 8, and 15
  • Pegaspargase 2500 units/m2 (maximum 3750 units) I.V. infusion over 1 to 2 hours or intramuscular (I.M.) injection on Days 4 (or Day 5 or Day 6) and 43
  • Cyclophosphamide 1000 mg/m2 I.V. infusion over 30 to 60 minutes on Day 29
  • Cytarabine 75 mg/m2 I.V. infusion over 1 to 3 hours or subcutaneous (SubQ) injection on Days 29, 30, 31, 32 and Days 36, 37, 38, and 39
  • 6-Thioguanine 60 mg/m2 oral tablets by mouth once daily (at least one hour after evening meal)  on Days 29 through 42 (=14 days in a row)
  • Methotrexate 15 mg intrathecal (I.T.) injection on Days 1, 29, and 36

Note: Individual doses may vary based upon your Doctor's recommendation, or drug availability.

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.