Yttrium Y 90 Anti-CD45 Monoclonal Antibody AHN-12 in Treating Patients With Advanced Leukemia
- Conditions
- LeukemiaMyelodysplastic Syndromes
- Interventions
- Biological: anti-CD45 monoclonal antibody AHN-12Radiation: yttrium Y 90 anti-CD45 monoclonal antibody AHN-12
- Registration Number
- NCT00618696
- Lead Sponsor
- Masonic Cancer Center, University of Minnesota
- Brief Summary
RATIONALE: Monoclonal antibodies can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Radioactive monoclonal antibodies, such as yttrium Y 90 monoclonal antibody, can find cancer cells and either kill them or carry cancer-killing substances to them without harming normal cells.
PURPOSE: This phase I trial is studying the side effects and best dose of a yttrium Y 90 monoclonal antibody and how much radiation is taken in by the organs in the body in treating patients with advanced leukemia or other hematologic disorder.
- Detailed Description
OBJECTIVES:
Primary
* To establish that a dose of 150 mg/m² of nonradiolabeled anti-CD45 monoclonal antibody AHN-12 results in normal biodistribution, normal-organ estimated radiation-absorbed dose of less than 20 Gy, and estimated radiation-absorbed dose of no more than 13 Gy to the red marrow.
Secondary
* To determine the maximum tolerated dose of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 (\^90Y-AHN-12).
* To determine the human anti-mouse antibody (HAMA) response.
* To define, preliminarily, the antitumor activity of \^90Y-AHN-12.
OUTLINE: This is a dose-escalation study of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 (\^90Y-AHN-12).
* Biodistribution: Patients receive nonradiolabeled monoclonal antibody AHN-12 IV and an imaging dose of indium Y 111 monoclonal antibody AHN-12 (\^111In-AHN-12) IV over 10 minutes on day 0. Patients undergo whole-body gamma-camera imaging immediately following infusion, at 4-6 hours, and on days 1, 3, 4, and 7. Blood samples are collected prior to each imaging for dosimetry calculations and pharmacokinetics.
Patients also undergo bone marrow biopsy 16-24 hours after infusion for dosimetry calculations. Patients with the expected biodistribution of \^111In-AHN-12, an estimated radiation-absorbed dose to the normal organ of \< 20 Gy, an estimated radiation-absorbed dose to the red marrow of ≤ 13 Gy, and a negative human anti-mouse antibody at day 7 proceed to the therapy portion.
* Treatment: Patients receive nonradiolabeled anti-CD45 monoclonal antibody AHN-12 IV over 60 minutes and escalating therapy doses of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 (\^90Y-AHN-12) IV over 10 minutes on day 7 or 8.
After completion of study treatment, patients are followed periodically for 1 year.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4
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Histologically confirmed CD45+ diseases:
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Acute lymphoblastic leukemia or acute myeloid leukemia (AML), meeting any of the following criteria:
- Primary refractory disease
- Relapsed disease, defined as persistent disease following a minimum of 2 different standard chemotherapy induction attempts at time of diagnosis or at relapse
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Acute myelogenous leukemia (AML), primary refractory or relapsed disease - defined as persistent disease after a minimum of two different standard chemotherapy induction attempts at time of diagnosis or relapse
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Advanced myelodysplastic syndrome (MDS) defined as > or = 15% bone marrow blasts following a minimum of one standard chemotherapy induction attempt
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AML arising from preexisting MDS, refractory - defined as persistent disease following a minimum of one standard chemotherapy induction attempt
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Chronic myelogenous leukemia (CML) following blast crisis (> or = 15% marrow blasts following a minimum of one standard chemotherapy induction attempt
-
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Peripheral leukemic blasts (by morphology) must be < 5,000/μL (hydroxyurea to control peripheral blast count allowed)
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Must have source of allogeneic stem cells (sibling, unrelated cord[s], or donor) identified prior to initiation of protocol therapy
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 or Karnofsky PS 60-100%
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Life expectancy > 12 weeks
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Total bilirubin ≤ 2.5 times upper limit of normal (ULN)
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aspartate aminotransferase (AST) and Alanine transaminase (ALT) ≤ 2.5 times upper limit of normal (ULN)
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Creatinine ≤ 1.3 mg/dL OR creatinine clearance ≥ 60 mL/min
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Left ventricular ejection fraction (LVEF) ≥ 45% by Multi Gated Acquisition Scan (MUGA) or echocardiogram (ECHO)
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Carbon Monoxide Diffusing Capacity (DLCO) (corrected) ≥ 50% of predicted
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Human anti-mouse antibody (HAMA) must be negative
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Not pregnant or nursing
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Fertile patients must use effective contraception
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Human immunodeficiency virus (HIV) negative
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Recovered from all prior therapy
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At least 7 days since prior biologic agents
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Bone marrow cellularity < 15%
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Known brain metastases or active central nervous system (CNS) disease
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History of allergic reactions attributed to compounds of similar chemical or biologic composition to ^90Y-AHN-12 or other agents used in study
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Uncontrolled illness, including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic or congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would limit compliance with study requirements
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Other concurrent investigational agents
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Prior allogeneic transplantation
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Less than 60 days since prior autologous transplantation with relapsed disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AHN-12 anti-CD45 monoclonal antibody AHN-12 2.0, 5.0, 7.5, 10.0 or 12.5 mCi/m\^2 of \^90Y-AHN-12 at Day 7/8 AHN-12 yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 2.0, 5.0, 7.5, 10.0 or 12.5 mCi/m\^2 of \^90Y-AHN-12 at Day 7/8
- Primary Outcome Measures
Name Time Method Biodistribution of nonradiolabeled anti-CD45 monoclonal antibody AHN-12 Within 1 hour, 4-6 hours, Days 1, 3, 4 and 7 post infusion
- Secondary Outcome Measures
Name Time Method Presence of human antibody to murine antibody at baseline and at 28 days, 90 days, and 6 months after completion of study treatment Dose-limiting toxicity and response at days 28 and 90 after completion of study treatment Maximum tolerated dose of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 Week 8
Trial Locations
- Locations (1)
Masonic Cancer Center at University of Minnesota
🇺🇸Minneapolis, Minnesota, United States