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

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Terminated

CT.gov ID

NCT00618696

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes	Biological: anti-CD45 monoclonal antibody AHN-12 Radiation: yttrium Y 90 anti-CD45 monoclonal antibody AHN-12	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

MT2005-13R - Phase I Open Label, Single Arm, Dose Escalation Trial to Evaluate the Biodistribution and Safety of AHN-12 in Patients With Advanced Leukemia

Study Start Date :

Jul 1, 2005

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AHN-12 2.0, 5.0, 7.5, 10.0 or 12.5 mCi/m^2 of ^90Y-AHN-12 at Day 7/8	Biological: anti-CD45 monoclonal antibody AHN-12 150 mg/m^2 cold antibody at Day 0 Other Names: ^111In-AHN-12 Radiation: yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 Dose per scheduled level; 2.5-12.5 mCi/m^2 Other Names: ^90Y-AHN-12

Arm

Intervention/Treatment

Experimental: AHN-12

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

Biological: anti-CD45 monoclonal antibody AHN-12

150 mg/m^2 cold antibody at Day 0

Other Names:

^111In-AHN-12

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

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

Other Names:

^90Y-AHN-12

Outcome Measures

Primary Outcome Measures

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

Maximum tolerated dose of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 [Week 8]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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