Yttrium Y 90 Anti-CD19 Antibody BU-12 in Patients With Advanced Relapsed or Refractory Acute Lymphoblastic Leukemia or Chronic Lymphocytic Leukemia

NCT ID: NCT00643240

Last Updated: 2017-11-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2010-04-30

Brief Summary

RATIONALE: Radiolabeled monoclonal antibodies can find cancer cells and carry cancer-killing substances to them without harming normal cells. This may be effective treatment for leukemia.

PURPOSE: This phase I trial is studying the best dose of yttrium Y 90-labeled monoclonal antibody BU-12 in treating patients with advanced relapsed or refractory acute lymphoblastic leukemia or chronic lymphocytic leukemia.

Detailed Description

OBJECTIVES:

Primary

• To determine the biodistribution of indium-111 BU-12 in patients with refractory CD19+ leukemia.

Secondary

• To determine the maximum tolerated dose of yttrium Y 90 anti-CD19 antibody BU-12
• Determine the human anti-mouse antibody (HAMA) response.
• To define, preliminarily, the antitumor activity of yttrium Y 90 anti-CD19 antibody BU-12.

OUTLINE: Patients receive yttrium Y 90 anti-CD19 antibody BU-12/indium-111 BU-12 IV over 60 minutes on day 0 and undergo whole-body imaging on days 0, 1, 3, 4, and 7. Patients also undergo blood collection and bone marrow biopsy periodically for dosimetry calculations and pharmacokinetics.

After completion of study treatment, patients are followed periodically for 2 years.

Conditions

Leukemia

Keywords

recurrent adult acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; refractory chronic lymphocytic leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

111 In-BU-12

111In-BU-12 is the 111Indium-labeled murine monoclonal antibody used for imaging and dosimetry.

Group Type: EXPERIMENTAL

yttrium Y 90 anti-CD19 monoclonal antibody BU12

Intervention Type: RADIATION

Patients in whom the biodistribution is as expected (unaltered) AND a HAMA response does not develop will receive a single dose of 90Y-BU-12 in a dose escalated manner to establish the maximum tolerated dose (MTD) of 90Y-BU-12 over 60 minutes on Day 0. A single course of BU-12 includes the imaging dose of 111In-BU-12 followed 7-8 days later by the therapy dose of 90YBU- 12.

111In-BU-12

Intervention Type: RADIATION

Patients receive indium-111 BU-12 IV over 60 minutes on day 0

Interventions

yttrium Y 90 anti-CD19 monoclonal antibody BU12

Patients in whom the biodistribution is as expected (unaltered) AND a HAMA response does not develop will receive a single dose of 90Y-BU-12 in a dose escalated manner to establish the maximum tolerated dose (MTD) of 90Y-BU-12 over 60 minutes on Day 0. A single course of BU-12 includes the imaging dose of 111In-BU-12 followed 7-8 days later by the therapy dose of 90YBU- 12.

Intervention Type: RADIATION

111In-BU-12

Patients receive indium-111 BU-12 IV over 60 minutes on day 0

Intervention Type: RADIATION

Other Intervention Names

90Y-BU-12; indium-111 BU-12

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed CD19-positive (> 25% by flow cytometry evaluation of bone marrow blasts) disease of 1 of the following types:

• Primary refractory or relapsed acute lymphoblastic leukemia (ALL) defined as persistent disease following a minimum of two different standard effective chemotherapy induction attempts at time of diagnosis or at relapse
• Chronic Lymphocytic leukemia (CLL) following blast crisis (≥15% bone marrow blasts following a minimum of one standard effective chemotherapy induction attempt)
• Human anti-mouse antibody (HAMA) must be negative
• Patients who have relapsed ≥ 60 days following an autologous or allogeneic transplant are eligible if all other eligibility criteria are met
• No active central nervous system (CNS) disease
• ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
• Life expectancy > 8 weeks
• Total bilirubin ≤ 2.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• LVEF ≥ 45% by MUGA/ECHO
• Oxygen saturation on room air > 92% and no oxygen requirement
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients mus use effective contraception

Exclusion Criteria

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to of yttrium Y 90 anti-CD19 antibody BU-12 or other agents used in study
• Uncontrolled illness including, but not limited to, any of the following:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements
• HIV-positive
• Active graft-vs-host disease
• Less than 4 weeks since prior agents and recovered
• Less than 7 days since prior therapy with any biologic agent, defined as a growth factor or cytokine
• Less than 3 months since prior antibody or biologic anticancer therapy (e.g., alemtuzumab or epratuzumab)
• Other concurrent investigational agents
• Patients with peripheral blasts > 5,000/uL may receive concurrent hydroxyurea

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brenda Weigel, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

MT2006-09

Identifier Type: OTHER

Identifier Source: secondary_id

UMN-0611M96887

Identifier Type: OTHER

Identifier Source: secondary_id

2006LS057

Identifier Type: -

Identifier Source: org_study_id