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
18 Years
N/A
Both
Leukemia, Myelodysplastic Syndromes
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Biodistribution of nonradiolabeled anti-CD45 monoclonal antibody AHN-12
Outcome Time Frame:
Within 1 hour, 4-6 hours, Days 1, 3, 4 and 7 post infusion
Safety Issue:
No
Principal Investigator
Linda J. Burns, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Masonic Cancer Center, University of Minnesota
Authority:
United States: Food and Drug Administration
Study ID:
2005LS039
NCT ID:
NCT00618696
Start Date:
July 2005
Completion Date:
December 2007
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- 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)
- Leukemia
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| Masonic Cancer Center at University of Minnesota | Minneapolis, Minnesota 55455 |
