AHN-12 Biodistribution in Advanced Leukemia

Inclusion Criteria:

• Patients must have one of the following histologically confirmed CD45+ diseases. If possible, AHN-12 positivity will be confirmed by flow cytometry on a recent bone marrow or a peripheral blood sample, if circulating blasts are present. It is preferable that peripheral leukemic blasts be <10,000/uL at time of enrollment; however, hydroxyurea may be given to control the peripheral blast count.

  • Acute myelogenous leukemia (AML), primary refractory or relapsed disease - Primary refractory disease is defined as persistent disease following a minimum of two different standard chemotherapy induction attempts at time of diagnosis. At time of relapse, patients must have failed one salvage chemotherapy regimen.
  • Refractory myelodysplastic syndrome (MDS) - defined as persistent disease following a minimum of one standard chemotherapy induction attempt.
  • AML arising from pre-existing MDS, refractory - defined as persistent disease following a minimum of one standard chemotherapy induction attempt.
  • Acute lymphoblastic leukemia (ALL), primary refractory or relapsed disease - Primary refractory disease is defined as persistent disease following a minimum of two different standard chemotherapy induction attempts at time of diagnosis. At time of relapse, patients must have failed one salvage chemotherapy regimen.
  • Chronic myelogenous leukemia (CML) following blast crisis - defined as persistent accelerated phase or blast phase of disease following a minimum of one standard chemotherapy induction attempt.
• Age ≥ 12 years Because these are investigational new agents and have never before been used in humans, children less than 12 years of age are not eligible for this phase I protocol but will be eligible for future pediatric phase I trials.
• Karnofsky Performance Status ≥ 60% (16 years and older) or Lansky Play Score ≥ 60 (<16 years)
• Life expectancy of > 12 weeks in the opinion of the enrolling medical provider

• Patients must have adequate organ function as defined below within 14 days of study enrollment:

  • Total bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 X upper limit of normal (ULN)
  • Creatinine ≤ 2.0
• Baseline left ventricular ejection fraction (LVEF ≥ 40% by ECHO (echocardiogram)
• Baseline Carbon Monoxide Diffusing Capacity (DLCO) (corrected) ≥ 50% of predicted. Testing required only if symptomatic or prior known impairment.
• Human anti-mouse antibody (HAMA) must be negative (perform on all patients regardless of prior therapies).
• Consent to adequate contraception. The effects of 90Y-AHN-12 on the developing fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Source of allogeneic stem cells must have been identified in event of severe myelosuppression
• Able to give written consent.
• Both men and women of all ethnic groups are eligible for this trial.

Exclusion Criteria:

• Ongoing grade 2 or greater non-hematologic toxicity due to previously administered therapies
• < 8 days from completion of therapy with any biologic agent
• Receiving any investigational agents
• Active central nervous system (CNS) leukemia are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. If CNS disease is clinically suspected, patients should have a lumbar puncture and/or appropriate radiographic studies performed to determine CNS status and study eligibility. Patients who have had their CNS disease treated and the cerebral spinal fluid (CSF) has been cleared of disease are eligible.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 90Y-AHN-12 or other agents used in study.
• Uncontrolled illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements in the opinion of the enrolling medical provider.
• Pregnant and breastfeeding women are excluded from this study because 90Y-AHN-12, being radioactive, as well as high dose chemotherapy and total body irradiation (TBI) have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 90Y-AHN-12, breastfeeding should be discontinued if the mother is treated with 90Y-AHN-12. These potential risks may also apply to other agents used in this study.
• Human immunodeficiency virus (HIV) positive patients: HIV positive patients are excluded from this study since: a) HIV-positive patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, and b) HIV-positive patients receiving combination anti-retroviral therapy may develop pharmacokinetic interactions with 90Y-AHN-12 or other agents administered during the study.
• < 60 days since an autologous transplant
• Bone marrow cellularity <5% (because of concern of myelosuppression)