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

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Terminated

CT.gov ID

NCT00643240

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Radiation: yttrium Y 90 anti-CD19 monoclonal antibody BU12 Radiation: 111In-BU-12	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Open Label, Single Arm Escalation Trial to Evaluate the Biodistribution and Safety of BU-12 in Patients With Advanced Leukemia

Study Start Date :

Jan 1, 2008

Actual Primary Completion Date :

Apr 1, 2010

Actual Study Completion Date :

Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 111 In-BU-12 111In-BU-12 is the 111Indium-labeled murine monoclonal antibody used for imaging and dosimetry.	Radiation: 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. Other Names: 90Y-BU-12 Radiation: 111In-BU-12 Patients receive indium-111 BU-12 IV over 60 minutes on day 0 Other Names: indium-111 BU-12

Arm

Intervention/Treatment

Experimental: 111 In-BU-12

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

Radiation: 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.

Other Names:

90Y-BU-12

Radiation: 111In-BU-12

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

Other Names:

indium-111 BU-12

Outcome Measures

Primary Outcome Measures

Biodistribution of indium-111 BU-12 [Immediately post infusion, 4-6 hours after infusion and Days 1, 3, 4 and 7 after infusion]
Perform a whole body scan acquiring both anterior and posterior images at a speed of 10 cm/min (20 minute scan) using a medium energy collimator, a 256 x 1024 computer acquisition matrix and acquisition photo peak settings of 172 and 247 keV with 15% windows.

Secondary Outcome Measures

Maximum tolerated dose of yttrium Y 90 anti-CD19 antibody BU-12 [Beginning Day 1 of treatment]
DLT will be defined as bone marrow aplasia > 6 weeks duration from the first treatment day; specifically, failure to recover peripheral ANC > 500/μL and platelets > 20,000/μL documented by bone marrow aplasia, not malignant infiltration - Any NCI CTCAE v 3.0 grade 3 non-hematologic toxicity except for allergic reactions to radiolabeled BU-12 will be dose limiting. If the BU-12 antibody is very allergenic, then ≥ grade 3 allergic reactions will be dose limiting.
Presence or absence of a human antibody to murine antibody [baseline, 28 and 60 days post therapy, and at 6 months post therapy]
Presence or absence of a human antibody to murine antibody at baseline, 28 and 60 days post therapy, and at 6 months post therapy
Number of Patients by Clinical Response [day 28 and day 60]
Patients evaluable for DLT will be assessed for response at day 28 and day 60 post therapy dose (event is whether or not the patient has a Complete Remission, Partial Remission, Stable Disease, Refractory Disease, Relapsed Disease). The proportion of patients by disease status will be reported.
Time to Clinical Response [Day 28, 60, 6 Months]
Time-to-event will be measured from date of therapy dose.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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