Yttrium Y 90 Anti-CD45 Monoclonal Antibody AHN-12 in Treating Patients With Advanced Leukemia

University of Minnesota (UMN)

Status and phase

Terminated

Phase 1

Conditions

Leukemia

Myelodysplastic Syndromes

Treatments

Biological: anti-CD45 monoclonal antibody AHN-12

Radiation: yttrium Y 90 anti-CD45 monoclonal antibody AHN-12

Study type

Interventional

Funder types

Other

Identifiers

NCT00618696

UMN-MT2005-13R (Other Identifier)

2005LS039

Details and patient eligibility

About

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.

Full 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.

Enrollment

4 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically confirmed CD45+ diseases:
- 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
- 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
- Advanced myelodysplastic syndrome (MDS) defined as > or = 15% bone marrow blasts following a minimum of one standard chemotherapy induction attempt
- AML arising from preexisting MDS, refractory - defined as persistent disease following a minimum of one standard chemotherapy induction attempt
- Chronic myelogenous leukemia (CML) following blast crisis (> or = 15% marrow blasts following a minimum of one standard chemotherapy induction attempt
Peripheral leukemic blasts (by morphology) must be < 5,000/μL (hydroxyurea to control peripheral blast count allowed)
Must have source of allogeneic stem cells (sibling, unrelated cord[s], or donor) identified prior to initiation of protocol therapy
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 or Karnofsky PS 60-100%
Life expectancy > 12 weeks
Total bilirubin ≤ 2.5 times upper limit of normal (ULN)
aspartate aminotransferase (AST) and Alanine transaminase (ALT) ≤ 2.5 times upper limit of normal (ULN)
Creatinine ≤ 1.3 mg/dL OR creatinine clearance ≥ 60 mL/min
Left ventricular ejection fraction (LVEF) ≥ 45% by Multi Gated Acquisition Scan (MUGA) or echocardiogram (ECHO)
Carbon Monoxide Diffusing Capacity (DLCO) (corrected) ≥ 50% of predicted
Human anti-mouse antibody (HAMA) must be negative
Not pregnant or nursing
Fertile patients must use effective contraception
Human immunodeficiency virus (HIV) negative
Recovered from all prior therapy
At least 7 days since prior biologic agents

Exclusion criteria

Bone marrow cellularity < 15%
Known brain metastases or active central nervous system (CNS) disease
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, 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
Other concurrent investigational agents
Prior allogeneic transplantation
Less than 60 days since prior autologous transplantation with relapsed disease