Slow accrual

Study Design:

This is a two-stage Phase II trial investigating the efficacy of Clofarabine, Cyclophosphamide and Etoposide in acute leukemia patients with detectable minimal residual disease (MRD) prior to allo-HCT. The primary objective is to determine the impact of the study treatment in eliminating the presence of minimal residual disease without causing a significant delay of allo-HCT due to treatment related toxicity. The intent of this study is to allow patients to proceed to transplant (independent of this study) within 42 days of Day 1 of Clofarabine based therapy.

Patients will be stratified at the time of enrollment based on diagnosis (ALL versus AML). Based on this two-stage optimal design, a maximum of 49 patients with ALL and a maximum of 49 patients with AML will be needed. For each disease cohort, 21 patients will be enrolled in stage 1. If at the end of stage 1, the criteria is met for activating stage 2 (based on success of clearing MRD, proceeding to transplant within 42 days and without excessive toxicity) for one or both groups, stage 2 will be activated with an additional 28 patients enrolled.

Inclusion Criteria:

• Diagnosis of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) with <5% blasts in the bone marrow (M1) by morphology and that meets one of the following criteria:

  • Flow cytometric evidence of MRD (≥ 0.1% leukemic blasts for ALL or <5% leukemic blasts for AML detected in the bone marrow) OR
  • Molecular/cytogenetic evidence of disease (FISH or PCR methodology) performed within 7 days
  • AND with the intent of going on to an allogeneic hematopoietic cell transplantation (allo-HCT) independent of this study

• Age 0 to 60 years

• Karnofsky Performance Status ≥ 50% for patients 16 years and older and Lansky Play Score ≥ 50 for patients under 16 years of age

• Patients must have a life expectancy ≥ 8 weeks as determined by the enrolling investigator

• Have acceptable organ function as defined within 7 days of study registration:

  • Renal: creatinine clearance ≥70mL/min/1.73m2 or serum creatinine based on age/gender
  • Hepatic: aspartate aminotransferase (ALT) < 5 x upper limit of normal (ULN) and total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
  • Cardiac: left ventricular ejection fraction ≥ 40% by echocardiogram (ECHO/MUGA)

• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. At least 14 days must have elapsed from prior chemotherapy; at least 7 days must have elapsed since receiving biological therapy.

Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor and at least 14 days since pegfilgrastim (Neulasta®) administration.

• Sexually active females of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment and for 2 months after the last dose of chemotherapy. Sexually active men must agree to use barrier contraceptive for the duration of treatment and for 2 months after the last dose of chemotherapy.
• Voluntary written consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care

Exclusion Criteria:

• Acute Promyelocytic Leukemia (APL)
• Active central nervous system (CNS) leukemia or known chloromatous disease
• Receiving or plans to receive concomitant chemotherapy, radiation therapy; immunotherapy or other anti-cancer therapy other than is specified in the protocol
• 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)
• Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
• Known allergy to any of the agents or their ingredients used in this study