Safety Study of CAT-8015 Immunooxin in Patients With HCL With Advance Disease

Sponsor

Cambridge Antibody Technology (Other)

Overall Status

Unknown status

CT.gov ID

NCT00462189

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: The CAT-8015 immunotoxin can bind tumor cells and kill them without harming normal cells. This may be an effective treatment for hairy cell leukemia(HCL) that has not responded to chemotherapy, surgery or radiation therapy.

PURPOSE: Phase I dose escalation study to determine the maximum tolerated dose of CAT-8015 immunotoxin in treating patients who have hairy cell leukemia (HCL) that has not responded to treatment.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Hairy Cell Leukemia HCL	Drug: Immunotoxin therapy Drug: CAT-8015 Immunotoxin Procedure: Biological therapy	Phase 1

Detailed Description

OUTLINE: Patients receive CAT-8015 IV over 30 minutes on days 1, 3, and 5 followed by rest. Treatment repeats every 4 weeks for up to a total of 10 courses in the absence of dose limiting toxicity, complete response or disease progression. Patients are followed at 1, 3, 6,12,15,18, 21, 24 months following the start of the last treatment cycle.

Cohorts of 3-6 patients each will receive escalating doses of recombinant CAT-8015 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose proceeding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, between16 to 25 new patients will be added to the MTD cohort depending on how well the CAT-8015 is tolerated.

Study Design

Study Type:

Interventional

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Multicenter, Dose Escalation Study of CAT-8015 in Patient With Relapsed or Refractory Hairy Cell Leukemia (HCL)

Study Start Date :

Apr 1, 2007

Outcome Measures

Primary Outcome Measures

Estimate the maximum dose that can be safely administered to a patient []
Characterize the toxicity profile of CAT-8015 []
Study the clinical pharmacology of CAT-8015 []
Observe anti-tumor activity, if any. []

Secondary Outcome Measures

To assess the immunogenic potential of CAT-8015 to induce antibodies []
To investigate the potential of biomarkers to predict any therapeutic or toxic response. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

DISEASE CHARACTERISTICS:

Confirmed diagnosis of hairy cell leukemia
Measurable disease

At least one of the following indications for treatment:

Neutropenia (ANC <1000 cells/µL)
Anemia (Hgb <10g/dL)
Thrombocytopenia (Plt <100,000/µL)
An absolute lymphocyte count of >20,000 cells/µL, or
Symptomatic splenomegaly
Patient's must have had at least 2 prior systemic therapies. There must have been at least 2 prior courses of purine analog, or 1 if the response to this course lasted <2 years, or if the patient had unacceptable toxicity to purine analog.

PATIENT CHARACTERISTICS:

Performance status • ECOG 0-2

Life expectancy

• Life expectancy of greater than 6 months, as assessed by the principal investigator

Other

Patients with other cancers who meet eligibility criteria and have had less than 5 years of disease free survival will be considered on a case-by-case basis
Ability to understand and sign informed consent
Female and male patients agree to use an approved method of contraception during the study

EXCLUSION CRITERIA:

Documented and ongoing central nervous system involvement with their malignant disease (history of CNS involvement is not an exclusion criterion)
History of bone marrow transplant
Pregnant or breast-feeding females
Patients whose plasma contains either a significant level of antibody to CAT-8015 as measured by ELISA, or antibody that neutralizes the binding of CAT-8015 to CD22 as measured by a competition ELISA.
HIV positive serology (due to increased risk of severe infection and unknown interaction of CAT-8015 with antiretroviral drugs)
Hepatitis B surface antigen positive
Uncontrolled, symptomatic, intercurrent illness including but not limited to: infections requiring systemic antibiotics, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements

Hepatic function: serum transaminases (either ALT or AST) or bilirubin:

• ≥ Grade 2, unless bilirubin is due to Gilbert's disease

Renal function: serum creatinine clearance ≤60mL/min as estimated by Cockroft-Gault formula

Hematologic function:

The ANC <1000/cmm, or platelet count <50,000/cmm, if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy)
Baseline coagulopathy > grade 3 unless due to anticoagulant therapy
A patient will not be excluded because of pancytopenia ≥ Grade 3, or erythropoietin dependence, if it is due to disease, based on the results of bone marrow studies

Pulmonary function:

• Patients with < 50% of predicted forced expiratory volume (FEV1) or <50% of predicted diffusing capacity for carbon monoxide (DLCO), corrected for hemoglobin concentration and alveolar volume. Note: Patients with no prior history of pulmonary illness are not required to have PFTs. FEV1 will be assessed following bronchodilator therapy.

Recent prior therapy:

Cytotoxic chemotherapy (except stable doses of prednisone), whole body electron beam radiation therapy, interferon, retinoids or other systemic therapy, or investigational therapy of the malignancy for 3 weeks prior to entry into the trial
Less than or equal to < 3 months prior monoclonal antibody therapy (i.e. rituximab)
Patients who have received or are receiving radiation therapy less than 3 weeks prior to study entry will be not be excluded providing the volume of bone marrow treated is less than 10% and also the patient has measurable disease outside the radiation port
Any history of pseudomonas-exotoxin (PE) immunotoxin administration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305
2	Cancer Center of Northwestern University	Chicago	Illinois	United States	60611
3	Warren Grant Megnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland	United States	20892
4	Klinika Hamtologii Uniwersytetu Medycznego (Medical University of Lodz)	Lodz		Poland
5	Royal Marsden Hospital and Institute of Cancer Research	Surrey		United Kingdom