Treatment Name: C10403 Consolidation
What is C10403 consolidation chemotherapy?
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 is usually considered more aggressive than regimens given to adults (40 years or older).
The entire C10403 chemotherapy regimen consists of 5 different treatment courses: induction, consolidation (this page), interim maintenance, delayed intensification, and maintenance.
C10403 consolidation (Course II) typically begins within 7 days after completion of the induction phase, but may start later if the good white blood cell or platelet count is too low.
The consolidation phase of C10403 consists of the following five medications:
- Vincristine (Oncovin®)
- Cyclophosphamide (Cytoxan®)
- Cytarabine (Ara-C)
- Pegaspargase (Oncaspar®)
- 6-Mercaptopurine (6-MP)
Alternative name: 10403
How does C10403 consolidation (Course II) 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 consolidation (Course II) therapy:
C10403 consolidation is given after the induction treatment course to eliminate remaining leukemia cells and maintain remission from the leukemia. The consolidation phase may also allow for a deeper remission originally obtained by the first course of induction therapy.The C10403 protocol is commonly given with the goal of cure.
- Cyclophosphamide intravenous (I.V.) infusion over 30 to 60 minutes on Days 1 and 29 (total of two doses total this course)
- Cytarabine I.V. infusion over 1 to 3 hours or subcutaneous (SubQ) injection on Days 1, 2, 3, 4, then 8 , 9, 10, 11, then 29, 30, 31, 32, then 36, 37, 38, 39 (total of sixteen doses of cytarabine this course)
- Vincristine I.V. push or I.V. infusion over 10 to 15 minutes on Days 15, 22, 43, and 50 (total of four doses total this course)
- Pegaspargase I.V. infusion over 1 to 2 hours or intramuscular (I.M.) injection on Days 15 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
- 6-Mercaptopurine oral tablets by mouth once daily (at least one hour after evening meal) on Days 1 through 14 and Days 29 through 42 (total of twenty-eight doses this course). 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 mercaptopurine
- Methotrexate intrathecal (I.T.) injection on Days 1, 8, 15, and 22 (total of four doses total this course)
Estimated total infusion time for this treatment:
- Up to 5 hours for days when cyclophosphamide and cytarabine are both given
- Up to 4 hours on days when just cytarabine is given
- Up to 3 hours on days when vincristine is given with pegaspargase I.V infusion (up to 2 hours if pegaspargase given by I.M. injection)
- Up to one hour for days when vincristine is given alone
- 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, or a drug reaction 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 consolidation chemotherapy is usually given in an outpatient infusion center, allowing the person to go home after each planned treatment. On occasion, C10403 consolidation may be given in the hospital if close monitoring is needed.
NOTE: 6-Mercaptopurine 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 consolidation chemo starting doses.
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 consolidation 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.
How often is monitoring needed?
Labs (blood tests) may be checked before treatment and periodically during treatment until stable. 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. Minimal residual disease, or MRD, uses your blood or bone marrow cells to see if any leukemia cells can still be detected in the body. MRD may be tested using either flow cytometry, quantitative polymerase chain reaction (qPCR), or both.
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 as planned, decrease doses of certain medications, or delay treatment until recovery.
- Continuous exposure to 6-mercaptopurine (6-MP), rather than frequent stopping and restarting, has been shown to have better anti-leukemia effect. If 6-MP is causing side effects to the point where it is difficult to take, talk with your doctor to see if reducing the dose may be safe, yet still effective
- It is usually recommend to swallow mercaptopurine tablets whole. On occasion, your doctor may have you split them in half. However, the dose of mercaptopurine 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 day of the week.
- Unless your doctor specifically tells you it is okay, you should NOT take allopurinol while taking 6-MP due to a drug interaction between these two medicines. If taken together, the allopurinol could lead to an unsafe build up of 6-MP in your body or cause the 6-MP to be less effective
- 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®). 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 prednisone, 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-mercaptopurine, called TPMT. In some cases, genetic testing for TPMT may recommended before or during treatment with 6-mercaptopurine 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 Consolidation, 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 Consolidation. Depending upon your income, they may be able to help cover the cost of:
- Cyclophosphamide IV
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 Consolidation 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.
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 Consolidation
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.
What are "adolescents and young adults (AYA)?
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, doctors use 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 an "intrathecal (I.T.) injection?
Intrathecal (I.T.) injection is a procedure where a needle is inserted into the spinal canal of the lower back to access the space that contains the cerebral spinal fluid (CSF). Typically, once the needle is inserted, a small amount of CSF is taken out and chemotherapy is then injected into the CSF. This is most often performed to treat cancer that is present in the CSF or to prevent cancer from invading the CSF. It is important that patients lie flat for 30 min - 1 hour after receiving an I.T. injection.
Common C10403 consolidation chemo starting doses
- Cyclophosphamide 1000 mg/m2 intravenous (I.V.) infusion over 30 to 60 minutes on Days 1 and 29 (total of two doses total this course)
- Cytarabine 75 mg/m2 I.V. infusion over 1 to 3 hours or subcutaneous (SubQ) injection on Days 1, 2, 3, 4, then 8 , 9, 10, 11, then 29, 30, 31, 32, then 36, 37, 38, 39 (total of sixteen doses of cytarabine this course)
- Vincristine 1.5 mg/m2 (maximum 2 mg) I.V. push or I.V. infusion over 10 to 15 minutes on Days 15, 22, 43, and 50 (total of four doses total this course)
- Pegaspargase 2500 units/m2 (maximum 3750 units) I.V. infusion over 1 to 2 hours or intramuscular (I.M.) injection on Days 15 and 43
- 6-Mercaptopurine 60 mg/m2/day oral tablets by mouth once daily (at least one hour after evening meal) on Days 1 through 14 and Days 29 through 42 (total of twenty-eight doses this course). Different amounts of tablets may need to be taken on certain days of the week so that 420 mg/m2/week is administered. Double check the prescribed daily dose each day before taking mercaptopurine
- Methotrexate 15 mg intrathecal (I.T.) injection on Days 1, 8, 15, and 22 (total of four doses total this course)
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.
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 status, 2) 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
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein
13) Serum glucose
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.
What is "TPMT"?
Thiopurine methyltranferase (TPMT) is an enzyme that is responsible for metabolizing certain medications such as mercaptopurine, thioguanine, and azathioprine. Although rare, some patient may have genetic alterations that cause a decrease in activity of the TPMT enzyme. In extremely rare cases, patients may not have any activity of this enzyme.
Testing for genetic alterations in TPMT is often recommended for patients that experience severe and unexpected side effects from therapy, with the most common effect being very low blood counts. If alterations in TPMT are detected, therapy with mercaptopurine, thioguanine, or azathioprine may need to be adjusted or even stopped.
1) Curran E, 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.