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Treatment Name: FLAG-IDA (Fludarabine + Ara-C + G-CSF + Ida­rubi­cin)

FLAG-IDA (Fludarabine + Ara-C + G-CSF + Ida­rubi­cin) is a Chemotherapy Regimen for Acute Myeloid Leukemia (AML)

How does FLAG-IDA chemotherapy work?
Each of the medications in the FLAG-IDA chemo regimen are designed to target and kill leukemia cells in the blood and bone marrow.

FL - Fludarabine
A - Ara-C (Cytarabine)
G - Granulocyte colony stimulating factor (G-CSF, filgrastim)
IDA - Idarubicin

Goals of therapy:
FLAG-IDA is given as induction chemotherapy to eliminate leukemia cells from the body and to decrease symptoms from AML, such as bleeding, bruising, and recurrent infections. It may be given with the goal of cure or to put the leukemia in remission so a bone marrow transplant can be performed.

Schedule

  • Fludarabine intravenous (I.V.) infusion over 30 minutes on Days 1, 2, 3, 4 and 5
  • Cytarabine I.V. infusion over four hours (starting four hours after fludarabine) on Days 1, 2, 3, 4 and 5
  • Idarubicin intravenous push over 10 - 15 minutes on Days 1, 2 and 3
  • G-CSF (Filgrastim) subcutaneous injection once daily starting 24 hours either the day before or the day of chemotherapy, and continuing daily until Day 5. In some instances, G-CSF may be restarted seven days after chemotherapy and continued until the neutrophil count returns to normal range

Estimated total infusion time for this treatment:

  • Up to five hours on Days 1 through 5; however, since fludarabine and cytarabine must be separated by four hours, it can take up to 9 hours to finish treatment each day
  • 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

A bone marrow biopsy is usually performed after treatment when white blood cells return to normal range to see if the leukemia is in remission. This may occur as early as Day 14, but some doctors prefer to wait until sometime between Day 21 to 28.

FLAG-IDA requires a 21 to 28 day stay in a hospital (sometimes longer) depending upon when white blood cell counts return to the normal range and also how well the side effects are tolerated and whether remission is achieved.

Only one cycle of FLAG-IDA is typically given; however, if remission is achieved, a second cycle of FLAG-IDA or a different chemotherapy regimen may subsequently (next) be given to obtain a deeper (better) response.

Click here for the common FLAG-Ida 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 side effects of FLAG-IDA are shown here. Side effects sometimes have percentage ranges [example: 35 – 49%] because they differed between clinical studies:

  • Fever (98%),
  • Liver injury (35 - 49%),
  • Infection (38 - 41%),
  • Sores in mouth (33 - 100%),
  • Skin rash (17 - 33%),
  • Nausea and vomiting (22 - 29%),
  • Diarrhea (17 - 24%),
  • Kidney injury (4 - 24%),
  • Bleeding (13 - 22%),
  • Decreased heart function (4%),
  • Swelling around the brain (2%),
  • Stroke (2%).

Side effect videos Side Effect Videos
AnemiaAnemiaNeutropenic FeverNeutropenic FeverPainPainNausea and VomitingNausea and VomitingDiarrheaDiarrheaBleedingBleedingHair LossHair LossBlood ClotsBlood ClotsConstipationConstipationFatigue Fatigue

Monitoring

How often is monitoring needed?
Labs (blood tests) may be checked before treatment, then daily or every other day for the first few weeks while in the hospital. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), lactate dehydrogenase (LDH), phosphorous, and uric acid, plus any others your doctor may order.

How often is imaging needed?
Imaging may be checked before treatment, or during the first month if there is concern for an infection or blood clot. Imaging may include: X-rays and computerized tomography (CT) scans. An echocardiogram or multigated acquisition (MUGA) scan may be performed before treatment to check your left ventricular ejection fraction (LVEF).

How might blood test results/imaging affect treatment?
Depending on the results of the bone marrow biopsy, your doctor may choose to continue therapy, change therapy, or not give you any more therapy and observe you closely.

ChemoExperts Tips

  • During the first few days of therapy, you will be monitored closely for tumor lysis syndrome (TLS). Signs of TLS are high levels of potassium, phosphorous and uric acid and low levels of calcium in the blood. Allopurinol is a medication commonly given at the start of therapy to prevent the development of high uric acid levels in the blood. Additional medications may need to be given if TLS develops
  • Corticosteroid eye drops, such as prednisolone eye drops, are often started before the first dose of cytarabine to prevent eye irritation known as conjunctivitis. Eye drops may be continued 48 to 72 hours after the last dose of cytarabine
  • Short term difficulty with writing, walking, or talking may occur but is rare and usually reversible. To prevent these problems, various neurological tests are done prior to each dose of cytarabine looking for early signs of toxicity. Examples of these tests include: follow an object with your eyes, repeat various phrases, sign your name, or walk a straight line
  • FLAG-IDA requires a long stay in the hospital. Try to be as active as possible by taking walks in the hallway, or using an exercise bicycle in the room, if available. This will hopefully speed time to recovery
  • All patients experience very low white blood cells, red blood cells, and platelets. On average, 8 red blood cell and 8 platelet transfusions are needed during induction treatment
  • An anti-fungal medication, such as posaconazole, may be prescribed to prevent a life-threatening invasive fungal infection
  • Reactivation of herpes simplex virus (HSV) can occur. Prophylactic (preventative) anti-viral medications such as acyclovir (Zovirax®), valacyclovir (Valtrex®), or famciclovir (Famvir®) should be taken during treatment
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • Clinical trials may exist for AML. 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 FLAG-IDA (Fludarabine + Ara-C + G-CSF + Ida­rubi­cin), 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 FLAG-IDA (Fludarabine + Ara-C + G-CSF + Ida­rubi­cin). Depending upon your income, they may be able to help cover the cost of:

  • Fludarabine
  • Cytarabine
  • Idarubicin

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 FLAG-IDA (Fludarabine + Ara-C + G-CSF + Ida­rubi­cin) 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 FLAG-IDA (Fludarabine + Ara-C + G-CSF + Ida­rubi­cin)

Individual Drug Label Information

Fludarabine (Fludara®)

  • Fludarabine is an intravenous infusion
  • Dosage adjustments may be required for decreased kidney function
  • Fludarabine can severely suppress bone marrow function resulting in very low white blood cells, low red blood cells, and low platelets
  • There have been reported cases of production of antibodies against red blood cells or platelets causing them to be destroyed. This can result in severe low red blood cell or platelet counts. Patients on fludarabine should be monitored for a condition called “hemolysis” or destruction of blood cells
  • Rare cases of neurological effects such as confusion, irritability, blindness, seizures, coma, or evendeath have occurred
  • Fludarabine should be avoided during pregnancy and breastfeeding
  • Can cause low white blood cells known as “CD4+ T-cells” leading to an increased risk of developing Pneumocystis Pneumonia. Medications that prevent Pneumocystis Pneumonia, such as Bactrim® (sulfamethoxazole/trimethoprim), may be used
General Fludarabine (Fludara) Side Effects
  • Low white and red blood cell count
  • Weakness and fatigue
  • Low platelet cell count 
  • Fever and infections due to low white blood cell count
  • Nausea and vomiting
  • Diarrhea and intestinal bleeding
  • General body pain
  • Mouth sores - stomatitis
  • Decreased appetite
  • Confusion
  • Nerve pain
  • Lung problems: cough, shortness of breath, bleeding in lungs, lung infections
  • Skin rash
  • Heart problems, heart swelling
  • Click on the fludarabine (Fludara) package insert below for reported side effects and possible drug interactions

Side Effect Videos
DiarrheaDiarrheaFatigue Fatigue BleedingBleedingPainPainAnemiaAnemiaNeutropenic 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.

Idarubicin (Idamycin®)

  • Idarubicin is administered as an intravenous infusion and is red in color
  • Is commonly infused over 10 – 15 minutes
  • 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 Idarubicin (Idamycin) Side Effects
  • Increases your risk of bleeding.  It is normal to receive red blood cell & platelet transfusions if receiving idarubicin
  • May cause nausea, vomiting, diarrhea, and mouth sores (stomatitis)
  • Leakage into skin or surrounding muscle may cause severe irritation (extravasation)
  • May temporarily turn urine orange
  • Causes hair loss, This is usually temporary and reversible
  • May increase the risk of infection due to decrease white blood cell count (neutropenia). It is normal to receive I.V. antibiotics after idarubicin is infused
  • Click on the idarubicin (Idamycin) package insert below for reported side effects and potential drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingHair LossHair LossFatigue Fatigue BleedingBleedingAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

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References

1) Pastore D, Specchia G, Carluccio P, et al. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003;82:231–235.

2) Parker JE, Pagliuca A, Mijovic A, et al. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol. 1997;99:939–944.

3) de la Rubia J, Regadera A, Martín G, et al. FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies. Leuk Res. 2002;26:725–730.

Created: January 8, 2017 Updated: January 8, 2017

What is Acute Myeloid Leukemia (AML)?

A disease of the myeloid cells found in the bone marrow. Myeloid cells are responsible for developing into mature white blood cells, red blood cells, and platelets. In AML, immature myeloid 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 this include fatigue, difficulty exercising, or easy bruising or bleeding.

Most cases of AML are considered “de novo” meaning that the cause is unknown. However, there are a few known risk factors for AML, such as exposure to radiation, various environmental toxins, and certain chemotherapy agents. There is no staging system for AML. Chromosomes (strands of DNA) 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 which therapy is appropriate for you.

What is Induction Chemotherapy?

An intensive cycle of chemotherapy that requires hospitalization. Induction chemotherapy often requires intense monitoring by hospital staff to ensure that infections are treated and blood or platelet transfusions are given when needed. The goal of induction chemotherapy is to achieve a complete remission, meaning no leukemia cells are detectable.

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 I.V. Push?

An intravenous medication that is usually prepared in a syringe and infused by vein over a short period of time, such as 15 minutes or less

Clinical Studies

If you are interested in reading the clinical trials results, please click on references below:

1) Pastore D, Specchia G, Carluccio P, et al. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003;82:231–235.

2) Parker JE, Pagliuca A, Mijovic A, et al. Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol. 1997;99:939–944.

3) de la Rubia J, Regadera A, Martín G, et al. FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies. Leuk Res. 2002;26:725–730.

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 the Left Ventricular Ejection Fraction (LVEF)?

The amount of blood pumped by the left ventrical (chamber) of the heart into the body with each heartbeat. Certain drugs can decrease heart function and result in less blood being pumped by each heartbeat than normal.

What is Tumor Lysis Syndrome?

Tumor lysis syndrome occurs when many cancer cells die quickly and release their contents into the bloodstream. Many times the body has the ability to flush these substances out through the kidneys or metabolize them via the liver. However, sometimes the body needs medicines to help eliminate these substances and to prevent organ damage.

Exercise Bicycle

What if a bicycle is not available? Some hospitals allow family members to purchase an exercise bicycle and bring it in fully assembled. Ask your nurse if this may be an option!

Common FLAG-Ida starting doses

  • Fludarabine 30 mg/m2 intravenous (I.V.) infusion over 30 minutes on Days 1, 2, 3, 4 and 5
  • Cytarabine 2000 mg/m2 I.V. infusion over 4 hours (starting 4 hours after fludarabine) on Days 1, 2, 3, 4 and 5
  • Idarubicin 10 mg/m2 intravenous push over 10 - 15 minutes on Days 1, 2 and 3
  • G-CSF (Filgrastim) subcutaneous injection once daily starting 24 hours either the day before or the day of chemotherapy, and continuing daily until Day 5. In some instances, G-CSF may be restarted 7 days after chemotherapy and continued until the neutrophil count returns to normal range

NOTE: If the creatinine clearance is between 30 - 70 mL/min, the dose of fludarabine may be reduced by 50%

Posaconazole

Posaconazole is an anti-fungal medication that has been shown in a large, randomized clinical trial to prevent life-threatening fungal infections in patients with AML receiving induction chemotherapy