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AHN-12 Biodistribution in Advanced Leukemia

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ClinicalTrials.gov Identifier: NCT01207076
Recruitment Status : Terminated (Slow accrual)
First Posted : September 22, 2010
Last Update Posted : December 5, 2017
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE September 21, 2010
First Posted Date  ICMJE September 22, 2010
Last Update Posted Date December 5, 2017
Study Start Date  ICMJE December 2013
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 21, 2010)
Optimal Dose of AHN-12 Non-radiolabeled Antibody [ Time Frame: Day 2 ]
doses of nonradiolabeled antibody are specified: 0.20, 0.40, 0.60, 0.80 and 1.00 mg/kg.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01207076 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2010)
  • Maximum Tolerated Dose (MTD) of 90Y-AHN-12 [ Time Frame: Within 14 days of achieving favorable biodistribution ]
    •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 ]
    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 ]
    Event is response to therapy: complete remission, partial remission, refractory or relapsed disease.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2010)
  • Maximum Tolerated Dose (MTD) of 90Y-AHN-12 [ Time Frame: Within 14 days of achieving favorable biodistribution ]
    •Determine the MTD of 90Y-AHN-12 for patients with a favorable biodistribution and a negative HAMA. Doses of radiolabeled antibody are specified starting dose level with dose increment of 2 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 ]
    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 ]
    Event is response to therapy: complete remission, partial remission, refractory or relapsed disease.
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE AHN-12 Biodistribution in Advanced Leukemia
Official Title  ICMJE 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
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • Acute Lymphoblastic Leukemia
  • Chronic Myelogenous Leukemia
Intervention  ICMJE 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.
Study Arms 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).
Intervention: Biological: 90Y-AHN-12
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 15, 2015)
8
Original Estimated Enrollment  ICMJE
 (submitted: September 21, 2010)
30
Actual Study Completion Date July 2014
Actual Primary Completion Date July 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender
Sexes Eligible for Study: All
Ages 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01207076
Other Study ID Numbers  ICMJE 2010LS030
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Linda Burns, M.D. Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP