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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


Phase 1
18 Years
N/A
Not Enrolling
Both
Leukemia, Myelodysplastic Syndromes

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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 MinnesotaMinneapolis, Minnesota  55455