Clinical trial NCT00618696: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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)
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2008-02-20
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Biodistribution of nonradiolabeled anti-CD45 monoclonal antibody AHN-12
timeFrame: Within 1 hour, 4-6 hours, Days 1, 3, 4 and 7 post infusion
Secondary outcomes:
measure: Maximum tolerated dose of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12
timeFrame: Week 8
measure: Presence of human antibody to murine antibody
timeFrame: at baseline and at 28 days, 90 days, and 6 months after completion of study treatment
measure: Dose-limiting toxicity and response
timeFrame: at days 28 and 90 after completion of study treatment
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: Linda J. Burns, MD
role: PRINCIPAL_INVESTIGATOR
References: