AHN-12 Biodistribution in Advanced Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Linda Burns, M.D., Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01207076
First received: September 21, 2010
Last updated: July 8, 2014
Last verified: July 2014
  Purpose

This study is a single institution phase I study for the treatment of patients with relapsed or refractory leukemia aged 12 years and older using 90Y-AHN-12.


Condition Intervention Phase
Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Acute Lymphoblastic Leukemia
Chronic Myelogenous Leukemia
Biological: 90Y-AHN-12
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Bio-availability Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Open Label, Single Arm, Dose Escalation Trial to Evaluate the Biodistribution and Safety of AHN-12 In Patients With Advanced Leukemia HM2010-05

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Optimal Dose of AHN-12 Non-radiolabeled Antibody [ Time Frame: Day 2 ] [ Designated as safety issue: Yes ]
    doses of nonradiolabeled antibody are specified: 0.20, 0.40, 0.60, 0.80 and 1.00 mg/kg.


Secondary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of 90Y-AHN-12 [ Time Frame: Within 14 days of achieving favorable biodistribution ] [ Designated as safety issue: Yes ]
    •Determine the MTD of 90Y-AHN-12 for patients with a favorable biodistribution and a negative human anti-mouse antibody (HAMA). Doses of radiolabeled antibody are specified starting dose level with dose increment of 2 gray (Gy) to maximum of 22 Gy.

  • Human Anti-Mouse Antibody (HAMA) Response [ Time Frame: 30 and 90 Days Post Therapy, Then Every 6 Months If Positive ] [ Designated as safety issue: No ]
    Event is whether or not the patient develops a HAMA response.

  • Anti-tumor Activity of 90Y-AHN-12 [ Time Frame: 30 and 90 Days Post Therapy ] [ Designated as safety issue: No ]
    Event is response to therapy: complete remission, partial remission, refractory or relapsed disease.


Estimated Enrollment: 30
Study Start Date: December 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: receiving AHN-12 and 90Y-AHN-12
Patients receiving nonradiolabeled cold AHN-12 (.20 mg/kg to 1.0 mg/kg) of at least one dose and up to a total of 3 dosimetry infusions (intervals no sooner than 8 days and up to 21 days).
Biological: 90Y-AHN-12

The intervention consists of two parts.

  1. The dose of cold AHN-12 to achieve favorable biodistribution through imaging using 111In-AHN-12.

    • Dose escalation of nonradiolabeled AHN-12:

    Dose level= -1 0.20 mg/kg, Dose level=1 0.40 mg/kg, Dose level=2 0.80 mg/kg, Dose level=3 1.20 mg/kg, Dose level=4 1.60 mg/kg, Dose level=5 2.00 mg/kg

  2. Phase I therapeutic dosing of cold AHN-12 at dose established plus 90Y-AHN-12.

    • the starting 90Y-AHN-12 dose level will be 4 Gy with the dose escalated in increments of 4 Gy to a maximum of 20 Gy.

Detailed Description:

A dose escalation schema will be used with the initial patient receiving the current lowest dose of nonradiolabeled AHN-12 (from 0.20 mg/kg to 1.0 mg/kg). If a favorable biodistribution is not achieved and the patient remains negative for HAMA, the infusion may be repeated up to two more times (with a one level increase in nonradiolabeled AHN-12 each time) in an attempt of achieving favorable biodistribution.

In order to achieve the primary objective of identifying the optimal nonradiolabeled dose of AHN-12 antibody for all patients, if the first patient at the current antibody dose does not achieve favorable biodistribution, the next patient(s) will be treated at the next higher dose level.

Patients achieving favorable biodistribution and remaining negative for HAMA will be eligible for the therapeutic component of this trial. Those not meeting these requirements will be taken off study and followed.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have one of the following histologically confirmed CD45+ diseases. If possible, AHN-12 positivity will be confirmed by flow cytometry on a recent bone marrow or a peripheral blood sample, if circulating blasts are present.

    • Acute myelogenous leukemia (AML), primary refractory or relapsed disease
    • Refractory myelodysplastic syndrome (MDS)
    • AML arising from pre-existing MDS, refractory
    • Acute lymphoblastic leukemia (ALL), primary refractory or relapsed disease
    • Chronic myelogenous leukemia (CML) following blast crisis
  • Age ≥ 12 years
  • Karnofsky Performance Status ≥ 60% (16 years and older) or Lansky Play Score ≥ 60 (<16 years)
  • Life expectancy of > 12 weeks in the opinion of the enrolling medical provider
  • Patients must have adequate organ function
  • Human anti-mouse antibody (HAMA) must be negative (perform on all patients regardless of prior therapies).
  • Consent to adequate contraception. The effects of 90Y-AHN-12 on the developing fetus are unknown.
  • Source of allogeneic stem cells must have been identified in event of severe myelosuppression
  • Able to give written consent.
  • Both men and women of all ethnic groups are eligible for this trial.

Exclusion Criteria:

  • Ongoing grade 2 or greater non-hematologic toxicity due to previously administered therapies
  • < 8 days from completion of therapy with any biologic agent
  • Receiving any investigational agents
  • Active central nervous system (CNS) leukemia are excluded from this clinical trial
  • 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, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements in the opinion of the enrolling medical provider.
  • Pregnant and breastfeeding women are excluded from this study because 90Y-AHN-12, being radioactive, as well as high dose chemotherapy and total body irradiation (TBI) have the potential for teratogenic or abortifacient effects.
  • Human immunodeficiency virus (HIV) positive patients:
  • < 60 days since an autologous transplant
  • Bone marrow cellularity <5% (because of concern of myelosuppression)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01207076

Contacts
Contact: Linda Burns, M.D. 612-624-8144 burns019@umn.edu

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Linda Burns, M.D.    612-624-8144    burns019@umn.edu   
Principal Investigator: Linda Burns, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Linda Burns, M.D. Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Linda Burns, M.D., Principal Investigator, Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01207076     History of Changes
Other Study ID Numbers: 2010LS030
Study First Received: September 21, 2010
Last Updated: July 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
CD45+ disease

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Acute
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders

ClinicalTrials.gov processed this record on September 18, 2014