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Treatment Name: CLAG-M (Cladribine + Cytarabine + G-CSF + Mitoxantrone)

CLAG-M (Cladribine + Cytarabine + G-CSF + Mitoxantrone) is a Chemotherapy Regimen for Acute Myeloid Leukemia (AML)

How does CLAG-M work for acute myeloid leukemia?
Each of the medications in CLAG-M are designed to target and kill leukemia cells in the blood and bone marrow. GCSF is given to "trick" leukemia cells into beginning the process to divide while chemotherapy is being given. Because cladribine, ara-C, and mitoxantrone chemotherapy medications work best when cells are dividing, GCSF causes more AML leukemia cells to die from chemotherapy.

CL – Cladribine
A – Ara-C (Cytarabine)
G – GCSF (Filgrastim)
M - Mitoxantrone

Goals of CLAG-M therapy for AML:
CLAG-M is typically given to patients with relapsed or refractory AML after one or more prior treatments. The goal of CLAG-M is to eliminate leukemia cells from the body and to decrease symptoms from AML, such as bleeding, bruising, and recurrent infections. If CLAG-M leads to a remission from the leukemia, some patients go on to recieve a bone marrow transplant which is given to cure the leukemia.


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Schedule for CLAG-M chemotherapy

  • Cladribine intravenous (I.V.) infusion over 2 hours on Days 1, 2, 3, 4, and 5
  • Cytarabine I.V. infusion over 4 hours (starting 2 hours after cladribine finishes) on Days 1, 2, 3, 4, and 5
  • Mitoxantrone I.V. infusion over 30 minutes on Days 1, 2, and 3
  • G-CSF (Filgrastim) subcutaneous injection once daily starting 24 hours the day before, or on the first 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 CLAG-M:

  • Up to 7 hours for Days 1, 2, 3, 4, and 5; however, since cladribine 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 and platelets return to the 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.

CLAG-M 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 or whether remission is achieved.

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

Click here for the common CLAG-M 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 CLAG-M are shown here:

All patients during treatment experience very low red blood cells [anemia], white blood cells [neutropenia], and platelets [thrombocytopenia]. In clinical studies, patient received an average of 6 units of red blood cell transfusions and 24 units of platelet transfusions. Patients are also at risk of neutropenic fever.

Most side effects from CLAG-M can be managed with medications. In order to be prepared for handling side effects from CLAG-M, please watch all side effect videos shown below.

Side effect videos Side Effect Videos
AnemiaAnemiaNeutropenic FeverNeutropenic FeverNausea and VomitingNausea and VomitingDiarrheaDiarrheaBleedingBleeding


How often is monitoring needed with CLAG-M?
Labs (blood tests) may be checked every day during treatment. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), blood phosphorus, uric acid, plus any others your doctor may order.

How often is imaging needed with CLAG-M?
Imaging may be checked if there are concerns for infection, bleeding, or other side effects. Imaging may include: X-rays, magnetic resonance imaging (MRI), or computerized tomography (CT) scans.

How might blood test results/imaging affect treatment with CLAG-M?
Depending upon the bone marrow biopsy results, your doctor may advise to proceed onto consolidation chemotherapy or to a bone marrow transplant once your normal blood cells recover. If remission has not been achieved, your doctor may advise to change therapies.

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: following an object with your eyes, repeating various phrases, signing your name, or walking in a straight line
  • CLAG-M 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
  • 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 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 CLAG-M (Cladribine + Cytarabine + G-CSF + Mitoxantrone), 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 CLAG-M (Cladribine + Cytarabine + G-CSF + Mitoxantrone). Depending upon your income, they may be able to help cover the cost of:

  • Cladribine
  • Cytarabine
  • Mitoxantrone

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 CLAG-M (Cladribine + Cytarabine + G-CSF + Mitoxantrone) 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 CLAG-M (Cladribine + Cytarabine + G-CSF + Mitoxantrone)

Individual Drug Label Information

Cladribine (2-CdA)

  • ​Cladribine is an intravenous infusion
  • Cladribine can severely suppress bone marrow function resulting in very low white blood cells, low red blood cells, and low platelets
  • Kidney toxicity may occur, but typically only occurs at doses higher than what are commonly used
  • 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
  • May cause fetal harm if given to pregnant women. Use effective contraception during therapy and avoid cladribine during pregnancy and breastfeeding
General side effects from cladribine (2-CdA)
  • Low red blood cells, white blood cells, and platelets
  • Kidney injury
  • Infection
  • Fever
  • Fatigue
  • Click on the cladribine (2-CdA) package insert below for reported side effects, possible drug interactions, and other cladribine prescribing information

Side Effect Videos
Fatigue Fatigue AnemiaAnemiaNeutropenic 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.

Mitoxantrone (Novantrone®)

  • Mitoxantrone is an intravenous infusion and is blue in color
  • Can affect heart function. A heart study (echocardiogram) may be required before receiving the first dose
  • Leakage into skin or surrounding muscle may cause severe irritation (extravasation)
  • Has been linked to the development of other cancers in a small number of people (1.6% chance at 10 years)
  • May cause fetal harm if given to pregnant women. Avoid mitoxantrone during pregnancy and while breastfeeding
General side effects from mitoxantrone (Novantrone®)
  • Low red blood cells, white blood cells, and platelets
  • Nausea and vomiting
  • May temporarily turn urine blue or green
  • Hair loss
  • Diarrhea
  • Fatigue
  • Infection
  • Click on the mitoxantrone (Novantrone®) package insert below for reported side effects, possible drug interactions, and other mitoxantrone prescribing information

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

See DailyMed package insert.

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1) Wierzbowska A, Robak T, Pluta A, et al. Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008;80:115-126.

Created: February 28, 2019 Updated: September 12, 2019

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.

Common CLAG-M starting doses

  • Cladribine 5 mg/m2 intravenous (I.V.) infusion over 2 hours on Days 1, 2, 3, 4 and 5
  • Cytarabine 2,000 mg/m2 I.V. infusion over 4 hours (starting 4 hours after cladribine) on Days 1, 2, 3, 4 and 5
  • Mitoxantrone 10 mg/m2 I.V. infusion over 30 minutes on Days 1, 2, and 3
  • G-CSF (Filgrastim) 300 mcg 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

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

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

14) Serum calcium

What is Tumor Lysis Syndrome (TLS)?

Tumor lysis syndrome, or TLS, 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.

Can I bring in an Exercise Bicycle for long hospital stays?

Some hospitals allow family members to purchase an exercise bicycle, or other exercise equipment, and bring it in fully assembled if exercise equipment is not already available. Ask your nurse or doctor if this may be an option!


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