Evaluation of the Anti-CD-33 Immunotoxin Hum-195/rGel in Patients With Advanced Myeloid Malignancies - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00038051

Purpose

The goal of this clinical research study is to find the highest safe dose of the anti-CD33 immunotoxin HuM-195/rGel that can be given to patients with advanced myeloid malignancies. This treatment will be given to patients whose leukemia has not responded to prior chemotherapy.

Condition	Intervention	Phase
Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia Myeloproliferative Disorders Anemia, Refractory, With Excess of Blasts	Drug: Hum-195/rGel	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Evaluation of the Anti-CD-33 Immunotoxin Hum-195/rGel in Patients With Advanced Myeloid Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Anemia Cancer Leukemia

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) [ Time Frame: Continuous assessment of safety throughout entire study period and determination of dose-limiting toxicities at end of two week evaluation period (4 weeks from start of therapy). ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	36
Study Start Date:	June 1999
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: HuM195/rGel	Drug: Hum-195/rGel Starting Dose = 3 mg/m2 twice weekly x 2 weeks.

Detailed Description:

Before therapy, all patients will be asked about their medical history, and a physical exam (with measurement of vital signs) will be performed. A chest X-ray and an electrocardiogram (ECG - a test to measure the electrical activity of the heart) will be performed. Blood (about 4 teaspoons) will be drawn for routine tests and blood clotting tests. Women who are able to become pregnant will have a urine pregnancy test done. A test will be done to measure the amount of oxygen in your blood by placing a monitoring device on your finger. Blood (about 1 teaspoon) will be taken to measure the amount of a protein that is present on the diseased cells. During the study period, the study staff will draw blood samples for routine tests, pharmacokinetic (PK) tests, and anti-drug antibody tests. Blood (about 1 teaspoon) will be drawn to measure the amount of a protein that is present on the diseased cells. A bone marrow sample will also be obtained before treatment and on Study Day 28.

Patients will receive four injections of the immunotoxin. The immunotoxin is designed to selectively destroy myeloid leukemia cells. The injections will be given through a vein twice weekly for two weeks. Patients will then be evaluated twice weekly for the next two weeks. If there has been improvement in the leukemia, or if the leukemia has remained stable and there have been no serious side effects of treatment, patients will then receive a second course of immunotoxin injections. These will again be given twice weekly for two weeks. Depending on the effectiveness against leukemia and the side effects, patients may receive maintenance treatment. This would also consist of two weekly injections given for two weeks followed by two weeks of observation. Maintenance therapy may continue for up to four months for partial response and up to two months for complete response.

This is an investigational study. Up to 36 patients will take part in this study.

Eligibility

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

Criteria

Inclusion Criteria:

Patients with relapsed or refractory AML, RAEB-t, RAEB, or CMML who failed at least one previous chemotherapy course. Patients with accelerated CML Ph+ or myeloid blastic crisis are eligible. Patients in accelerated phase of non-Philadelphia chromosome + myeloproliferative disorders are also eligible:
- P. vera,
- myelofibrosis
- essential thrombocytopenia with >5% blasts in the blood or bone marrow.
Male or female 18 yrs of age or older who have provided written informed consent
Tumor cells must be = or > 80% CD33 positive by flow cytometry
For women of childbearing potential (i.e. exclude post-menopausal women, women who have been surgically sterilized), adequate birth control methods must be used. Acceptable birth control methods are limited to oral contraceptives, implants, diaphragm, IUD or spermicide used with a condom
WBC count <10,000/ml for AML, MDS, and myeloproliferative disorders and up to 30,000 for accelerated CML
No cytotoxic chemotherapy for the two weeks prior to entering the study
No evidence of residual toxic effects grade 2 or higher from prior chemotherapy
Patients with proven bacterial infection are not eligible until resolution of the infection (patient afebrile, not on steroids). Patients with active fungal infections are eligible only if evidence of response to antifungal medications is documented and they do not have fever exceeding 38°C
Creatinine - Patients should have values = or < 1.5 times the upper limit of laboratory normal values
Liver function - Patients should have serum bilirubin values = or < 2.0 times the upper limit of laboratory normal values. Patients should have SGOT and/or SGPT levels = or < 2.5 times the upper limit of laboratory normal values
Cardiac function - Patients with cardiovascular disease should be < NYHA classification III
Pulmonary function - O2 saturation should be = or > 92% without exogenous O2 administered.
Neurologic function - Patients should have normal central nervous system function as well as normal motor function consistent with = or < Grade 1 toxicity. Patients should have peripheral sensory function damage (neuropathy) not exceeding Grade 1 toxicity

Exclusion Criteria:

Women who are pregnant or lactating

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00038051

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Jorge Cortes, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

M.D. Anderson's Website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00038051 History of Changes
Other Study ID Numbers:	DM98-342
Study First Received:	May 24, 2002
Last Updated:	December 14, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

Acute Myeloid Leukemia
AML
Chronic Myelomonocytic Leukemia
CMML
Myeloproliferative Disorders

Refractory Anemia with Excess of Blasts
RAEB-t
RAEB
Hum-195/rGel

Additional relevant MeSH terms:

Anemia
Anemia, Refractory
Anemia, Refractory, with Excess of Blasts
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Acute
Myeloproliferative Disorders
Hematologic Diseases

Myelodysplastic Syndromes
Bone Marrow Diseases
Neoplasms by Histologic Type
Neoplasms
Myelodysplastic-Myeloproliferative Diseases
Immunotoxins
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012