Clinical trial NCT00643240: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Leukemia
Keywords: recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
refractory chronic lymphocytic leukemia
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2008-03-26
Enrollment: 1
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Biodistribution of indium-111 BU-12
timeFrame: Immediately post infusion, 4-6 hours after infusion and Days 1, 3, 4 and 7 after infusion
Secondary outcomes:
measure: Maximum tolerated dose of yttrium Y 90 anti-CD19 antibody BU-12
timeFrame: Beginning Day 1 of treatment
measure: Presence or absence of a human antibody to murine antibody
timeFrame: baseline, 28 and 60 days post therapy, and at 6 months post therapy
measure: Number of Patients by Clinical Response
timeFrame: day 28 and day 60
measure: Time to Clinical Response
timeFrame: Day 28, 60, 6 Months
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Brenda Weigel, MD
role: PRINCIPAL_INVESTIGATOR
References: