Yttrium Y 90 Anti-CD45 Monoclonal Antibody AHN-12 in Treating Patients With Advanced Leukemia or Other Hematologic Disorder - Full Text View

Sponsors and Collaborators:	Masonic Cancer Center, University of Minnesota National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00618696

Purpose

RATIONALE: Monoclonal antibodies can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Radioactive monoclonal antibodies, such as yttrium Y 90 monoclonal antibody, can find cancer cells and either kill them or carry cancer-killing substances to them without harming normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of a yttrium Y 90 monoclonal antibody and how much radiation is taken in by the organs in the body in treating patients with advanced leukemia or other hematologic disorder.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Biological: anti-CD45 monoclonal antibody AHN-12 Other: pharmacological study Procedure: biopsy Procedure: radionuclide imaging Radiation: yttrium Y 90 anti-CD45 monoclonal antibody AHN-12	Phase I

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	MT2005-13R - Phase I Open Label, Single Arm, Dose Escalation Trial to Evaluate the Biodistribution and Safety of AHN-12 in Patients With Advanced Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Nuclear Scans Radiation Therapy

Drug Information available for: Immunoglobulins Globulin, Immune

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Biodistribution of nonradiolabeled anti-CD45 monoclonal antibody AHN-12 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Maximum tolerated dose of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 [ Designated as safety issue: Yes ]
Presence of human antibody to murine antibody at baseline and at 28 days, 90 days, and 6 months after completion of study treatment [ Designated as safety issue: No ]
Dose-limiting toxicity and response at days 28 and 90 after completion of study treatment [ Designated as safety issue: Yes ]

Estimated Enrollment:	18
Study Start Date:	July 2005
Estimated Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To establish that a dose of 150 mg/m² of nonradiolabeled anti-CD45 monoclonal antibody AHN-12 results in normal biodistribution, normal-organ estimated radiation-absorbed dose of less than 20 Gy, and estimated radiation-absorbed dose of no more than 13 Gy to the red marrow.

Secondary

To determine the maximum tolerated dose of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 (^90Y-AHN-12).
To determine the human anti-mouse antibody (HAMA) response.
To define, preliminarily, the antitumor activity of ^90Y-AHN-12.

OUTLINE: This is a dose-escalation study of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 (^90Y-AHN-12).

Biodistribution: Patients receive nonradiolabeled monoclonal antibody AHN-12 IV and an imaging dose of indium Y 111 monoclonal antibody AHN-12 (^111In-AHN-12) IV over 10 minutes on day 0. Patients undergo whole-body gamma-camera imaging immediately following infusion, at 4-6 hours, and on days 1, 3, 4, and 7. Blood samples are collected prior to each imaging for dosimetry calculations and pharmacokinetics.

Patients also undergo bone marrow biopsy 16-24 hours after infusion for dosimetry calculations. Patients with the expected biodistribution of ^111In-AHN-12, an estimated radiation-absorbed dose to the normal organ of < 20 Gy, an estimated radiation-absorbed dose to the red marrow of ≤ 13 Gy, and a negative human anti-mouse antibody at day 7 proceed to the therapy portion.

Treatment: Patients receive nonradiolabeled anti-CD45 monoclonal antibody AHN-12 IV over 60 minutes and escalating therapy doses of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 (^90Y-AHN-12) IV over 10 minutes on day 7 or 8. After completion of study treatment, patients are followed periodically for 1 year.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of 1 of the following:
- Acute lymphoblastic leukemia or acute myeloid leukemia (AML), meeting any of the following criteria:
  - Primary refractory disease
  - Relapsed disease, defined as persistent disease following a minimum of 2 different standard chemotherapy induction attempts at time of diagnosis or at relapse
- Refractory AML arising from pre-existing myelodysplastic syndromes (MDS), defined as persistent disease after a minimum of 1 standard chemotherapy induction attempt
- Advanced MDS or chronic myelogenous leukemia after blast crisis, defined as ≥ 15% bone marrow blasts after a minimum of one standard chemotherapy induction attempt
Peripheral leukemic blasts (by morphology) must be < 5,000/μL (hydroxyurea to control peripheral blast count allowed)
CD45-positive disease
No bone marrow cellularity < 15%
Must have source of allogeneic stem cells (sibling, unrelated cord[s], or donor) identified prior to initiation of protocol therapy
No known brain metastases or active CNS disease

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
Life expectancy > 12 weeks
Total bilirubin ≤ 2.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN
Creatinine ≤ 1.3 mg/dL OR creatinine clearance ≥ 60 mL/min
LVEF ≥ 45% by MUGA or ECHO
DLCO (corrected) ≥ 50% of predicted
Human anti-mouse antibody (HAMA) must be negative
Not pregnant or nursing
Fertile patients must use effective contraception
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to
- 90Y-AHN-12 or other agents used in study
No uncontrolled illness, including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic or congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would limit compliance with study requirements
HIV negative

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from all prior therapy
At least 7 days since prior biologic agents
No other concurrent investigational agents
No prior allogeneic transplantation
At least 60 days since prior autologous transplantation with relapsed disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00618696

Locations

United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Linda J. Burns, MD

Masonic Cancer Center, University of Minnesota

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000585145, UMN-2005LS039, UMN-MT2005-13R
Study First Received:	February 19, 2008
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00618696 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
secondary acute myeloid leukemia
previously treated myelodysplastic syndromes
blastic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia

adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)

Study placed in the following topic categories:

Blast Crisis
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunologic Factors
Precancerous Conditions
Hematologic Diseases
Myelodysplastic Syndromes
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Recurrence
Antibodies, Monoclonal
Leukemia

Antibodies
Acute Myelocytic Leukemia
Preleukemia
Acute Myeloid Leukemia, Adult
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasm Metastasis
Chronic Myelogenous Leukemia
Bone Marrow Diseases
Congenital Abnormalities
Acute Lymphoblastic Leukemia
Immunoglobulins

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Disease
Immunologic Factors
Precancerous Conditions
Hematologic Diseases
Physiological Effects of Drugs
Myelodysplastic Syndromes
Pharmacologic Actions
Antibodies, Monoclonal

Leukemia
Preleukemia
Neoplasms
Antibodies
Pathologic Processes
Syndrome
Bone Marrow Diseases
Immunoglobulins

ClinicalTrials.gov processed this record on September 11, 2009