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

NCT ID: NCT00618696

Last Updated: 2017-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-07-31

Study Completion Date

2007-12-31

Brief Summary

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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

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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.

Conditions

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Leukemia Myelodysplastic Syndromes

Keywords

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recurrent adult acute lymphoblastic leukemia recurrent adult acute myeloid leukemia secondary acute myeloid leukemia previously treated myelodysplastic syndromes blastic phase chronic myelogenous leukemia relapsing chronic myelogenous leukemia adult acute myeloid leukemia with 11q23 (MLL) abnormalities adult acute myeloid leukemia with inv(16)(p13;q22) adult acute myeloid leukemia with t(15;17)(q22;q12) adult acute myeloid leukemia with t(16;16)(p13;q22) adult acute myeloid leukemia with t(8;21)(q22;q22)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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AHN-12

2.0, 5.0, 7.5, 10.0 or 12.5 mCi/m\^2 of \^90Y-AHN-12 at Day 7/8

Group Type EXPERIMENTAL

anti-CD45 monoclonal antibody AHN-12

Intervention Type BIOLOGICAL

150 mg/m\^2 cold antibody at Day 0

yttrium Y 90 anti-CD45 monoclonal antibody AHN-12

Intervention Type RADIATION

Dose per scheduled level; 2.5-12.5 mCi/m\^2

Interventions

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anti-CD45 monoclonal antibody AHN-12

150 mg/m\^2 cold antibody at Day 0

Intervention Type BIOLOGICAL

yttrium Y 90 anti-CD45 monoclonal antibody AHN-12

Dose per scheduled level; 2.5-12.5 mCi/m\^2

Intervention Type RADIATION

Other Intervention Names

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^111In-AHN-12 ^90Y-AHN-12

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Masonic Cancer Center, University of Minnesota

Principal Investigators

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Linda J. Burns, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

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Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

Other Identifiers

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UMN-MT2005-13R

Identifier Type: OTHER

Identifier Source: secondary_id

2005LS039

Identifier Type: -

Identifier Source: org_study_id