Targeted Atomic Nano-Generators (Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195) in Patients With Advanced Myeloid Malignancies - Full Text View

Purpose

The purpose of this study is to find a safe dose of actinium-225 when it is labeled to HuM195. This will be done with a "phase I trial," in which a preset schedule of doses gets more powerful for each new group of patients as the trial progresses. If too many serious side effects are seen with a certain dose, no one will be treated with a higher dose, and some additional patients may be treated with a lower dose to make sure that this dose is safe. The starting dose of actinium-225 in this study is less than doses that are known to be safe in animals.

Antibodies are proteins that are produced by the immune system and help the body to fight foreign substances, such as bacteria or viruses. HuM195 was made by putting human leukemia cells into mice. Most of the mouse parts of this antibody were replaced with human parts. Only the part of the antibody that binds to the leukemia cells was kept from the mouse. HuM195 attaches to leukemia cells but does not attach to most normal cells. It can kill small amounts of disease by identifying the leukemia cells as "foreign." HuM195 has worked less well against large amounts of leukemia since the normal immune cells needed to kill leukemia cells are lowered in most patients with leukemia.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndrome	Biological: ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Trial of Targeted Atomic Nano-Generators (Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195) in Patients With Advanced Myeloid Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia Myelodysplastic Syndromes

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

To determine the maximum tolerated dose of 225Ac-HuM195 that can be administered to patients with advanced myeloid leukemias. [ Time Frame: conclusion of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine the pharmacokinetics and dosimetry of 225Ac-HuM195. [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]
To determine the biological effects of 225Ac-HuM195, including its ability to produce complete remissions. [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	July 2005
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 This is a phase I, dose-escalation trial. The starting dose level will be 0.5 μCi/kg of 225Ac-HuM195. Three to six patients will be treated at each dose level, and dose escalation will proceed if less than 33% of patients in a cohort experience dose limiting toxicity. Six patients will be treated at the maximum tolerated dose	Biological: ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195 A single infusion of 225Ac-HuM195 will be administered at a starting dose of 0.5 μCi/kg. Additionally, 100 mCi of 213Bi-HuM195 have been administered with full dose cytarabine (200 mg/m2 daily for 5 days) without dose-limiting toxicity.Serial sampling of blood, urine, and bone marrow will be performed following treatment to determine the toxicity, pharmacokinetics, immunogenicity, and antileukemic effects. Three to six patients will be treated at each dose level. Dose escalation will proceed if less than 33% of patients in a cohort experience dose-limiting toxicity.Patients will be followed until completion of therapy as outlined in the study, loss to follow-up, death, or until the day the patient is removed from the study.

Arms

Assigned Interventions

Experimental: 1

This is a phase I, dose-escalation trial. The starting dose level will be 0.5 μCi/kg of 225Ac-HuM195. Three to six patients will be treated at each dose level, and dose escalation will proceed if less than 33% of patients in a cohort experience dose limiting toxicity. Six patients will be treated at the maximum tolerated dose

Biological: ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195

A single infusion of 225Ac-HuM195 will be administered at a starting dose of 0.5 μCi/kg. Additionally, 100 mCi of 213Bi-HuM195 have been administered with full dose cytarabine (200 mg/m2 daily for 5 days) without dose-limiting toxicity.Serial sampling of blood, urine, and bone marrow will be performed following treatment to determine the toxicity, pharmacokinetics, immunogenicity, and antileukemic effects. Three to six patients will be treated at each dose level. Dose escalation will proceed if less than 33% of patients in a cohort experience dose-limiting toxicity.Patients will be followed until completion of therapy as outlined in the study, loss to follow-up, death, or until the day the patient is removed from the study.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have one of the following pathologically confirmed diagnoses:
AML in relapse,
AML refractory to at least 2 courses of standard induction chemotherapy or one course of high-dose cytarabine-containing induction chemotherapy,
CML in accelerated phase or myeloid blast crisis that has progressed after treatment with imatinib and a second generation tyrosine kinase inhibitor (e.g., dasatinib or nilotinib)
RAEB with International Prognostic Scoring System (IPSS) score ≥ 2.5, or - CMMOL with IPSS score ≥ 2.5 refractory to or relapsed after a hypomethylating agent (e.g., azacitidine or decitabine) refractory to or relapsed after a hypomethylating agent (e.g., azacitidine or decitabine).
Greater than 25% of bone marrow blasts must be CD33 positive.
Patients must have a life expectancy of at least 6 weeks and a Karnofsky performance status of ≥ 60%.
Adequate renal function as demonstrated by a serum creatinine ≤ 1.5 mg/dl, a creatinine clearance > 60 ml/min, and < 1 gram urinary protein/24 hours.
Adequate hepatic function as demonstrated by a bilirubin ≤ 1.5 mg/dl (unless attributable to leukemia or Gilbert's disease) and alkaline phosphatase and AST ≤ 2.5 times the upper limit of normal.

Exclusion Criteria:

Untreated AML, regardless of prognostic features.
Treatment with chemotherapy or biologic therapy within 3 weeks of 225Ac- HuM195 administration. Hydroxyurea is permitted but must be discontinued prior to treatment on study. Patients must have recovered from the effects of previous treatment.
Treatment with radiation therapy within 6 weeks of 225Ac-HuM195 administration. Patients must have recovered from the effects of previous treatment.
Active serious infections not controlled by antibiotics.
Pregnant women or women who are breast-feeding.
Concurrent active malignancy requiring therapy.
Clinically significant cardiac disease (NY Heart Association Class III or IV)or pulmonary disease.
Patients with HLA-compatible donor bone marrow who are immediate candidates for bone marrow transplantation.
Patients who are candidates for alternative treatments of known effectiveness.
Patients eligible for protocols of higher priority.
Patients previously treated with any monoclonal antibody for any reason.
Active CNS leukemia
Other serious or life-threatening conditions deemed unacceptable by the principal investigator.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00672165

Contacts

Contact: Dan Douer, MD	212-639-2471
Contact: Steven Larson, MD	212-639-7373

Locations

United States, New York
Memorial Sloan Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Dan Douer, MD 212-639-2471
Contact: Steven Larson, MD 212 639-7373
Principal Investigator: Dan Douer, MD

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Actinium Pharmaceuticals

Investigators

Principal Investigator:

Dan Douer, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00672165 History of Changes
Other Study ID Numbers:	02-017, NCI CA33049
Study First Received:	May 2, 2008
Last Updated:	December 21, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:

MAB HUM 195 ACTINIUM-225 LABELED
HEMATOPOIETIC SYSTEM
02-017

Additional relevant MeSH terms:

Leukemia
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases

Precancerous Conditions
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013