Phase I Trial of Targeted Atomic Nano-Generators (Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195) in Patients With Advanced Myeloid Malignancies
- Patients must have one of the following pathologically confirmed diagnoses:
- AML in relapse,
- AML refractory to at least 2 courses of standard induction chemotherapy or one course
of high-dose cytarabine-containing induction chemotherapy,
- CML in accelerated phase or myeloid blast crisis that has progressed after treatment
with imatinib and a second generation tyrosine kinase inhibitor (e.g., dasatinib or
- RAEB with International Prognostic Scoring System (IPSS) score ≥ 2.5, or - CMMOL with
IPSS score ≥ 2.5 refractory to or relapsed after a hypomethylating agent (e.g.,
azacitidine or decitabine) refractory to or relapsed after a hypomethylating agent
(e.g., azacitidine or decitabine).
- Greater than 25% of bone marrow blasts must be CD33 positive.
- Patients must have a life expectancy of at least 6 weeks and a Karnofsky performance
status of ≥ 60%.
- Adequate renal function as demonstrated by a serum creatinine ≤ 1.5 mg/dl, a
creatinine clearance > 60 ml/min, and < 1 gram urinary protein/24 hours.
- Adequate hepatic function as demonstrated by a bilirubin ≤ 1.5 mg/dl (unless
attributable to leukemia or Gilbert's disease) and alkaline phosphatase and AST ≤ 2.5
times the upper limit of normal.
- Untreated AML, regardless of prognostic features.
- Treatment with chemotherapy or biologic therapy within 3 weeks of 225Ac- HuM195
administration. Hydroxyurea is permitted but must be discontinued prior to treatment
on study. Patients must have recovered from the effects of previous treatment.
- Treatment with radiation therapy within 6 weeks of 225Ac-HuM195 administration.
Patients must have recovered from the effects of previous treatment.
- Active serious infections not controlled by antibiotics.
- Pregnant women or women who are breast-feeding.
- Concurrent active malignancy requiring therapy.
- Clinically significant cardiac disease (NY Heart Association Class III or IV)or
- Patients with HLA-compatible donor bone marrow who are immediate candidates for bone
- Patients who are candidates for alternative treatments of known effectiveness.
- Patients eligible for protocols of higher priority.
- Patients previously treated with any monoclonal antibody for any reason.
- Active CNS leukemia
- Other serious or life-threatening conditions deemed unacceptable by the principal