T2007-002 Clofarabine, Etoposide, Cyclophosphamide in Relapsed Acute Myelogenous Leukemia (AML)
Condition: Relapsed Acute Myelogenous Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Clofarabine; Etoposide; Cyclophosphamide; Filgrastim; Cytarabine
Intervention description: 40 mg/m2/day IV over 2 hours (given at hours 0 to 2) on days 1 through 5.; 100 mg/m2/day IV over 2 hours (given at hours 2 to 4) on days 1 through 5.; 440 mg/m2/day IV as a 30-60 minute infusion (given at hours 4 to 5) on days 1 through 5.; Administered in Courses 1 and 2 only. 5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is > 1000 x 2 days.; Given intrathecally on day 1 at the dose defined by age below:
30 mg for patients age 1-1.99 50 mg for patients age 2-2.99 70 mg for patients >3 years of age
Intervention MeSH terms: Cytarabine; Cyclophosphamide; Etoposide; Clofarabine; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 1 Year
Maximum age: 21 Years
Healthy volunteers: No
Keywords: relapsed; relapse; refractory; AML; Acute myelogenous leukemia; Relapsed AML

Summary:

      Clofarabine is a drug approved by the FDA (Food and Drug Administration) for treating
      children (age 1-21) with leukemia. This research study will use clofarabine with two other
      cancer fighting drugs. Clofarabine will be used together with etoposide (VePesid®, VP-16) and
      cyclophosphamide (Cytoxan®).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age: patients must be ≥ 1 and ≤ 21 years of age at the of study entry.

          -  Diagnosis:

               -  Patients must have a diagnosis of first or second relapse or refractory acute
                  myelogenous leukemia (AML) according to WHO classification with ≥ 5% blasts in
                  the bone marrow, with or without extramedullary disease.

               -  Patients may have CNS 1 or CNS 2 disease but not CNS 3.

          -  Performance Level: Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for
             patients ≤ 16 years of age.

          -  Prior Therapy:

               -  Patients must have fully recovered from the acute toxic effects of all prior
                  chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

               -  Patient has not received more than 2 previous induction attempts. (Frontline
                  therapy is included in this count).

               -  Patients must have adequate venous access.

               -  At least 1 year must have elapsed since hematopoietic stem cell transplant (HSCT)
                  and patients must not have active GVHD.

          -  Reproductive Function

               -  Female patients of childbearing potential must have a negative serum pregnancy
                  test confirmed within 2 weeks prior to enrollment.

               -  Female patients with infants must agree not to breastfeed their infants while on
                  this study.

               -  Male and female patients of child-bearing potential must agree to use an
                  effective method of contraception approved by the investigator during the study
                  and for a minimum of 6 months after study treatment.

          -  Renal and Hepatic Function:

        Patient must have adequate renal and hepatic functions as indicated by the following
        laboratory values:

          -  Patients must have a normal calculated creatinine clearance.

               -  Pediatric Population (age <18): Calculated creatinine clearance ≥ 90
                  ml/min/1.73m2 as calculated by the Schwartz formula for estimated glomerular
                  filtration rate (GFR) where GFR (ml/min/1.73 m2) = k*Height (cm)/serum creatinine
                  (mg/dl). k is a proportionality constant which varies with age and is a function
                  of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of
                  age; 0.55 children and adolescent girls; and 0.70 adolescent boys.

               -  Adult Population (age ≥18): Serum creatinine ≤1.0 mg/dL; if serum creatinine >1.0
                  mg/dL, then the estimated glomerular filtration rate (GFR) must be >60
                  mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease
                  equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x
                  (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black.

          -  Total bilirubin <1.5 x ULN for age and conjugated/direct serum bilirubin ≤ ULN for age
             if total bilirubin is elevated.

          -  Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5 × ULN.

          -  Alkaline phosphatase ≤ 2.5 × ULN.

        Exclusion Criteria:

          -  Patients with Down Syndrome.

          -  Prior treatment with Clofarabine.

          -  Previous history of veno-occlusive disease (VOD) or findings consistent with a
             diagnosis of VOD, defined as: conjugated serum bilirubin > 1.4 mg/dL AND unexplained
             weight gain greater than 10% of baseline weight or ascites AND hepatomegaly or right
             upper quadrant pain without another explanation, OR reversal of portal vein flow on
             ultrasound, OR pathological confirmation of VOD on liver biopsy.

          -  Patients who have a history of cirrhosis of the liver or who are positive for
             hepatitis B core antibody (anti-HBc) or have a positive test for hepatitis C antibody
             (anti-HCV).

          -  Patient has received TBI.

          -  If it has been less than 1 year since the patient had a HSCT.

          -  Infection Criteria

               -  Patients with a systemic fungal, bacterial, viral, or other infection not
                  controlled (defined as exhibiting ongoing signs/symptoms related to the infection
                  and without improvement, despite appropriate antibiotics or other treatment).

               -  Positive blood culture within 48 hours of study registration.

               -  Patient required supplemental oxygen or vasopressors within 48 hours of study
                  (Oxygen after anesthesia for procedures is ok).

          -  Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy,
             or immunotherapy other than as specified in the protocol.

          -  Use of investigational agents within 30 days or any anticancer therapy within 2 weeks
             before planned drug initiation with the exception of hydroxyurea or intrathecal
             therapy given with the diagnostic lumbar puncture.

          -  Have any other severe concurrent disease, or have a history of serious organ
             dysfunction or disease involving the heart, kidney, liver, or other organ system that
             may place the patient at undue risk to undergo treatment.

          -  Pregnant or lactating patients.

          -  Any significant concurrent disease, illness, psychiatric disorder or social issue that
             would compromise patient safety or compliance, interfere with consent, study
             participation, follow up, or interpretation of study results.

          -  Have had a diagnosis of another malignancy, unless the patient has been disease-free
             for at least 3 years following the completion of curative intent therapy with the
             following exceptions:

               -  Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical
                  intraepithelial neoplasia, regardless of the disease-free duration, are eligible
                  for this study if definitive treatment for the condition has been completed.

               -  Patients with organ-confined prostate cancer with no evidence of recurrent or
                  progressive disease based on prostate-specific antigen (PSA) values are also
                  eligible for this study if hormonal therapy has been initiated or a radical
                  prostatectomy has been performed.