AHN-12 Biodistribution in Advanced Leukemia

This study is currently recruiting participants.
Verified October 2013 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: October 11, 2013
Last verified: October 2013
  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. All patients must test negative for the human anti-mouse antibody (HAMA) and remain negative after each infusion to continue on study. In addition, a source of allogeneic stem cells (sibling, unrelated donor or cord) must have been identified in event of severe myelosuppression.


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: May 2011
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AHN-12 Treated Patients
Patients receiving nonradiolabeled 90Y-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

A dose escalation schema will be used with the initial patient receiving the current lowest dose of nonradiolabeled AHN-12. 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.

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 to two more times (with a one level increase in nonradiolabeled AHN-12 each time) in an attempt of achieving favorable biodistribution.


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. It is preferable that peripheral leukemic blasts be <10,000/uL at time of enrollment; however, hydroxyurea may be given to control the peripheral blast count.

    • Acute myelogenous leukemia (AML), primary refractory or relapsed disease - Primary refractory disease is defined as persistent disease following a minimum of two different standard chemotherapy induction attempts at time of diagnosis. At time of relapse, patients must have failed one salvage chemotherapy regimen.
    • Refractory myelodysplastic syndrome (MDS) - defined as persistent disease following a minimum of one standard chemotherapy induction attempt.
    • AML arising from pre-existing MDS, refractory - defined as persistent disease following a minimum of one standard chemotherapy induction attempt.
    • Acute lymphoblastic leukemia (ALL), primary refractory or relapsed disease - Primary refractory disease is defined as persistent disease following a minimum of two different standard chemotherapy induction attempts at time of diagnosis. At time of relapse, patients must have failed one salvage chemotherapy regimen.
    • Chronic myelogenous leukemia (CML) following blast crisis - defined as persistent accelerated phase or blast phase of disease following a minimum of one standard chemotherapy induction attempt.
  • Age ≥ 12 years Because these are investigational new agents and have never before been used in humans, children less than 12 years of age are not eligible for this phase I protocol but will be eligible for future pediatric phase I trials.
  • 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 as defined below within 14 days of study enrollment:

    • Total bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 X upper limit of normal (ULN)
    • Creatinine ≤ 2.0
  • Baseline left ventricular ejection fraction (LVEF ≥ 40% by ECHO (echocardiogram)
  • Baseline Carbon Monoxide Diffusing Capacity (DLCO) (corrected) ≥ 50% of predicted. Testing required only if symptomatic or prior known impairment.
  • 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. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • 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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. If CNS disease is clinically suspected, patients should have a lumbar puncture and/or appropriate radiographic studies performed to determine CNS status and study eligibility. Patients who have had their CNS disease treated and the cerebral spinal fluid (CSF) has been cleared of disease are eligible.
  • 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. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 90Y-AHN-12, breastfeeding should be discontinued if the mother is treated with 90Y-AHN-12. These potential risks may also apply to other agents used in this study.
  • Human immunodeficiency virus (HIV) positive patients: HIV positive patients are excluded from this study since: a) HIV-positive patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, and b) HIV-positive patients receiving combination anti-retroviral therapy may develop pharmacokinetic interactions with 90Y-AHN-12 or other agents administered during the study.
  • < 60 days since an autologous transplant
  • Bone marrow cellularity <5% (because of concern of myelosuppression)
  Contacts and Locations
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: October 11, 2013
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on April 23, 2014