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

Primary Purpose

Leukemia

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

yttrium Y 90 anti-CD19 monoclonal antibody BU12

111In-BU-12

About this trial

This is an interventional treatment trial for Leukemia focused on measuring recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia, refractory chronic lymphocytic leukemia

Eligibility Criteria

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

Sites / Locations

Masonic Cancer Center at University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

111 In-BU-12

Arm Description

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

Outcomes

Primary Outcome Measures

Biodistribution of indium-111 BU-12

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

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

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

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

Time-to-event will be measured from date of therapy dose.

Full Information

NCT ID

NCT00643240

First Posted

March 25, 2008

Last Updated

November 27, 2017

Sponsor

Masonic Cancer Center, University of Minnesota

1. Study Identification

Unique Protocol Identification Number

NCT00643240

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

November 2017

Overall Recruitment Status

Terminated

Why Stopped

Due to slow accrual

Study Start Date

January 2008 (undefined)

Primary Completion Date

April 2010 (Actual)

Study Completion Date

April 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

111 In-BU-12

Arm Type

Experimental

Arm Description

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

Intervention Type

Radiation

Intervention Name(s)

yttrium Y 90 anti-CD19 monoclonal antibody BU12

Other Intervention Name(s)

90Y-BU-12

Intervention Description

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

Intervention Name(s)

111In-BU-12

Other Intervention Name(s)

indium-111 BU-12

Intervention Description

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

Primary Outcome Measure Information:

Title

Biodistribution of indium-111 BU-12

Description

Time Frame

Immediately post infusion, 4-6 hours after infusion and Days 1, 3, 4 and 7 after infusion

Secondary Outcome Measure Information:

Title

Maximum tolerated dose of yttrium Y 90 anti-CD19 antibody BU-12

Description

Time Frame

Beginning Day 1 of treatment

Title

Presence or absence of a human antibody to murine antibody

Description

Presence or absence of a human antibody to murine antibody at baseline, 28 and 60 days post therapy, and at 6 months post therapy

Time Frame

baseline, 28 and 60 days post therapy, and at 6 months post therapy

Title

Number of Patients by Clinical Response

Description

Time Frame

day 28 and day 60

Title

Time to Clinical Response

Description

Time-to-event will be measured from date of therapy dose.

Time Frame

Day 28, 60, 6 Months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Brenda Weigel, 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-CD19 Antibody BU-12 in Patients With Advanced Relapsed or Refractory Acute Lymphoblastic Leukemia or Chronic Lymphocytic Leukemia

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