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AHN-12 Biodistribution in Advanced Leukemia

Primary Purpose

Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
90Y-AHN-12
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring CD45+ disease

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Masonic Cancer Center, University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

receiving AHN-12 and 90Y-AHN-12

Arm Description

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).

Outcomes

Primary Outcome Measures

Optimal Dose of AHN-12 Non-radiolabeled Antibody
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
•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
Event is whether or not the patient develops a HAMA response.
Anti-tumor Activity of 90Y-AHN-12
Event is response to therapy: complete remission, partial remission, refractory or relapsed disease.

Full Information

First Posted
September 21, 2010
Last Updated
December 3, 2017
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT01207076
Brief Title
AHN-12 Biodistribution in Advanced Leukemia
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual
Study Start Date
December 2013 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia
Keywords
CD45+ disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
receiving AHN-12 and 90Y-AHN-12
Arm Type
Experimental
Arm Description
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 Type
Biological
Intervention Name(s)
90Y-AHN-12
Intervention Description
The intervention consists of two parts. 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 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.
Primary Outcome Measure Information:
Title
Optimal Dose of AHN-12 Non-radiolabeled Antibody
Description
doses of nonradiolabeled antibody are specified: 0.20, 0.40, 0.60, 0.80 and 1.00 mg/kg.
Time Frame
Day 2
Secondary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of 90Y-AHN-12
Description
•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.
Time Frame
Within 14 days of achieving favorable biodistribution
Title
Human Anti-Mouse Antibody (HAMA) Response
Description
Event is whether or not the patient develops a HAMA response.
Time Frame
30 and 90 Days Post Therapy, Then Every 6 Months If Positive
Title
Anti-tumor Activity of 90Y-AHN-12
Description
Event is response to therapy: complete remission, partial remission, refractory or relapsed disease.
Time Frame
30 and 90 Days Post Therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Linda Burns, M.D.
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

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AHN-12 Biodistribution in Advanced Leukemia

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