t2007-002 clofarabine, etoposide, cyclophosphamide in relapsed acute myelogenous leukemia (aml)

Conditions: Relapsed Acute Myelogenous Leukemia

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®).

clofarabine, etoposide and cyclophosphamide have been used together in a phase i study to find out the highest doses of these drugs that can be safely given to children with relapsed or refractory leukemia. this study is a phase ii study which will use the drugs to study how well these drugs work against aml. this study will also examine the safety of this drug combination.

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.

Keywords: relapsed relapse refractory aml acute myelogenous leukemia relapsed aml