Patient case: 11-year-old male with Peutz-Jeghers syndrome; genetic feature: STK11

Clinical trial: Clofarabine With Cytarabine for Patients With Minimal Residual Disease Positive Leukemia

Summary: This study will test the ability of clofarabine + cytarabine to eliminate minimal residual disease (MRD) in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patients whose bone marrows exhibit complete remission by morphology. The toxicity profile of this regimen will be evaluated in addition to toxicity experienced by patients who proceed to stem cell transplant. Overall length of remission will also be collected.

Detailed description: Recent studies have demonstrated that even low levels of minimum residual disease (MRD) (>0.01% abnormal blasts) after aggressive re-induction therapy indicate a relatively poor outcome in relapsed acute lymphoblastic leukemia (ALL) patients, including those who proceed to allogeneic stem cell transplant (alloSCT). A similarly poor prognosis was seen in pediatric acute myelogenous leukemia patients with sub-morphologic disease prior to alloSCT. Studies to identify therapies that can eliminate persistent leukemia, have low toxicity profiles and can serve as a bridge to transplant are needed.
  This study will test the ability of clofarabine + cytarabine to eliminate minimal residual disease (MRD) in acute myelogenous leukemia and acute lymphoblastic leukemia patients whose bone marrows exhibit complete remission by morphology. The toxicity profile of this regimen will be evaluated in addition to toxicity experienced by patients who proceed to stem cell transplant. Overall length of remission will also be collected.

Eligibility: Inclusion Criteria: Patients must meet all of the following criteria to be eligible to participate in the study.
  Patients must be ≥1 and ≤ 21 years of age when enrolled onto this study.
  -  Diagnosis (Patient must have all of the following)
  -  Patients must have a diagnosis of relapsed acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL)
  -  Patient must have an M1 marrow based upon a recovered marrow with less than 5% blasts by conventional morphology
  -  Patient must have minimal residual disease (MRD) detected by either multidimensional or conventional flow cytometry greater than 0.1% and less than 5% following any re-induction attempt
  -  Patients must have a central nervous system (CNS) disease status of 1
  -  Patient must have an absolute neutrophil count (ANC) >500/μL off cytokine support for at least 24 hours and platelets >50,000 K/μL without platelet transfusion in the past seven days
  -  Karnofsky > 50% for patients > 10 years of age and Lansky > 50% for patients ≤ 10 years of age.
  -  Patient must have adequate venous access.
  -  Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
  -  At least 21 days must have elapsed from prior chemotherapy, at least 7 days must have elapsed since receiving biological therapy.
  -  It must be at least 90 days from any higher dose cytarabine therapy (>1 gm/ m2/day).
  -  Patients must have a normal calculated creatinine clearance
  -  Patient must have
  1. Conjugated (direct) serum bilirubin ≤ 1.5 x upper limit of normal (ULN) for age.
  2. Alanine transaminase (ALT) ≤ 2.5 × ULN for age.
  3. Alkaline phosphatase ≤ 2.5 × ULN for age.
  4. Serum amylase ≤ 1.5 ULN for age.
  5. Serum Lipase is ≤ ULN for age.
  -  Patient must have a shortening fraction > 28% or an ejection fraction > 50%.
  -  Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed 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.
  -  Patient must agree to submission of blood and bone marrow for assessment of minimal residual disease (MRD).
  -  All patients and/or their parents or legal guardians must sign a written informed consent.
  Exclusion Criteria:Patients who meet any of the following criteria will be excluded from participating in the study.
  -  Patients with previous hematopoietic stem cell transplant (HSCT) within previous six months.
  -  Patients who have had prior treatment with clofarabine.
  -  Patients with CNS2 or CNS 3 disease or bulky chloromatous disease.
  -  Patients with Down Syndrome.
  -  Patients with a previous history of veno-occlusive disease (VOD) or findings consistent with a diagnosis of VOD.
  -  Patients with a systemic fungal, bacterial, viral, or other infection not controlled.
  -  Use of investigational agents within 30 days of planned treatment on this protocol.
  -  Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy, immunotherapy or other anti-cancer therapy other than is specified in the protocol.
  -  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:
  1. Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intra-epithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed.
  2. 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.

Relevance to patient case: not relevant