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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


Phase 1
12 Years
N/A
Open (Enrolling)
Both
Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia

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Trial Information

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


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.


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)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Bio-availability Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Optimal Dose of AHN-12 Non-radiolabeled Antibody

Outcome Description:

doses of nonradiolabeled antibody are specified: 0.20, 0.40, 0.60, 0.80 and 1.00 mg/kg.

Outcome Time Frame:

Day 2

Safety Issue:

Yes

Principal Investigator

Linda Burns, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota

Authority:

United States: Food and Drug Administration

Study ID:

2010LS030

NCT ID:

NCT01207076

Start Date:

May 2011

Completion Date:

October 2015

Related Keywords:

  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • Acute Lymphoblastic Leukemia
  • Chronic Myelogenous Leukemia
  • CD45+ disease
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

Masonic Cancer Center, University of MinnesotaMinneapolis, Minnesota  55455