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

Primary Purpose

Leukemia, Myelodysplastic Syndromes

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
anti-CD45 monoclonal antibody AHN-12
yttrium Y 90 anti-CD45 monoclonal antibody AHN-12
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Masonic Cancer Center at University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AHN-12

Arm Description

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

Outcomes

Primary Outcome Measures

Biodistribution of nonradiolabeled anti-CD45 monoclonal antibody AHN-12

Secondary Outcome Measures

Maximum tolerated dose of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12
Presence of human antibody to murine antibody
Dose-limiting toxicity and response

Full Information

First Posted
February 19, 2008
Last Updated
November 27, 2017
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT00618696
Brief Title
Yttrium Y 90 Anti-CD45 Monoclonal Antibody AHN-12 in Treating Patients With Advanced Leukemia
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 Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Terminated
Why Stopped
Replaced with another study
Study Start Date
July 2005 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myelodysplastic Syndromes
Keywords
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AHN-12
Arm Type
Experimental
Arm Description
2.0, 5.0, 7.5, 10.0 or 12.5 mCi/m^2 of ^90Y-AHN-12 at Day 7/8
Intervention Type
Biological
Intervention Name(s)
anti-CD45 monoclonal antibody AHN-12
Other Intervention Name(s)
^111In-AHN-12
Intervention Description
150 mg/m^2 cold antibody at Day 0
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 anti-CD45 monoclonal antibody AHN-12
Other Intervention Name(s)
^90Y-AHN-12
Intervention Description
Dose per scheduled level; 2.5-12.5 mCi/m^2
Primary Outcome Measure Information:
Title
Biodistribution of nonradiolabeled anti-CD45 monoclonal antibody AHN-12
Time Frame
Within 1 hour, 4-6 hours, Days 1, 3, 4 and 7 post infusion
Secondary Outcome Measure Information:
Title
Maximum tolerated dose of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12
Time Frame
Week 8
Title
Presence of human antibody to murine antibody
Time Frame
at baseline and at 28 days, 90 days, and 6 months after completion of study treatment
Title
Dose-limiting toxicity and response
Time Frame
at days 28 and 90 after completion of study treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Linda J. Burns, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center at University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

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

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