AHN-12 Biodistribution in Advanced Leukemia

Acute Lymphoblastic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01207076
• Other study ID #: 2010LS030
• Status: Terminated
• Phase: Phase 1
• First received: September 21, 2010
• Last updated: December 3, 2017
• Start date: December 2013
• Est. completion date: July 2014

Study information

• Verified date: December 2017
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

Biological:
• 90Y-AHN-12
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.

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 2
Secondary	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.	Within 14 days of achieving favorable biodistribution
Secondary	Human Anti-Mouse Antibody (HAMA) Response	Event is whether or not the patient develops a HAMA response.	30 and 90 Days Post Therapy, Then Every 6 Months If Positive
Secondary	Anti-tumor Activity of 90Y-AHN-12	Event is response to therapy: complete remission, partial remission, refractory or relapsed disease.	30 and 90 Days Post Therapy