- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00025415
Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction
A Phase I Pharmacokinetic Study of STI571 in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction
Study Overview
Status
Conditions
- Primary Myelofibrosis
- Polycythemia Vera
- Essential Thrombocythemia
- Chronic Myelomonocytic Leukemia
- Recurrent Adult Acute Myeloid Leukemia
- Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
- Nodal Marginal Zone B-cell Lymphoma
- Recurrent Adult Burkitt Lymphoma
- Recurrent Adult Diffuse Large Cell Lymphoma
- Recurrent Adult Diffuse Mixed Cell Lymphoma
- Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
- Recurrent Adult Immunoblastic Large Cell Lymphoma
- Recurrent Adult Lymphoblastic Lymphoma
- Recurrent Grade 1 Follicular Lymphoma
- Recurrent Grade 2 Follicular Lymphoma
- Recurrent Grade 3 Follicular Lymphoma
- Recurrent Mantle Cell Lymphoma
- Recurrent Marginal Zone Lymphoma
- Splenic Marginal Zone Lymphoma
- Waldenström Macroglobulinemia
- Unspecified Adult Solid Tumor, Protocol Specific
- Secondary Acute Myeloid Leukemia
- Untreated Adult Acute Myeloid Leukemia
- Anaplastic Large Cell Lymphoma
- Angioimmunoblastic T-cell Lymphoma
- Monoclonal Gammopathy of Undetermined Significance
- Accelerated Phase Chronic Myelogenous Leukemia
- Childhood Myelodysplastic Syndromes
- Chronic Phase Chronic Myelogenous Leukemia
- Intraocular Lymphoma
- Previously Treated Myelodysplastic Syndromes
- Recurrent Adult Acute Lymphoblastic Leukemia
- Recurrent Adult Hodgkin Lymphoma
- Recurrent Adult T-cell Leukemia/Lymphoma
- Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
- Recurrent Mycosis Fungoides/Sezary Syndrome
- Recurrent Small Lymphocytic Lymphoma
- Refractory Multiple Myeloma
- Relapsing Chronic Myelogenous Leukemia
- Secondary Myelodysplastic Syndromes
- Small Intestine Lymphoma
- Prolymphocytic Leukemia
- Refractory Chronic Lymphocytic Leukemia
- Stage IV Adult Burkitt Lymphoma
- Stage IV Adult Diffuse Large Cell Lymphoma
- Stage IV Adult Diffuse Mixed Cell Lymphoma
- Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
- Stage IV Adult Hodgkin Lymphoma
- Stage IV Adult T-cell Leukemia/Lymphoma
- Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
- Stage IV Grade 1 Follicular Lymphoma
- Stage IV Grade 2 Follicular Lymphoma
- Stage IV Grade 3 Follicular Lymphoma
- Stage IV Mantle Cell Lymphoma
- Stage IV Marginal Zone Lymphoma
- Stage IV Mycosis Fungoides/Sezary Syndrome
- Stage IV Small Lymphocytic Lymphoma
- Chronic Neutrophilic Leukemia
- Gastrointestinal Stromal Tumor
- Refractory Hairy Cell Leukemia
- T-cell Large Granular Lymphocyte Leukemia
- Acute Undifferentiated Leukemia
- Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
- Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
- Primary Systemic Amyloidosis
- Primary Central Nervous System Non-Hodgkin Lymphoma
- Stage IV Adult Immunoblastic Large Cell Lymphoma
- Stage IV Adult Lymphoblastic Lymphoma
- Untreated Adult Acute Lymphoblastic Leukemia
- Progressive Hairy Cell Leukemia, Initial Treatment
- Stage IV Chronic Lymphocytic Leukemia
- Untreated Hairy Cell Leukemia
- de Novo Myelodysplastic Syndromes
- Blastic Phase Chronic Myelogenous Leukemia
- Meningeal Chronic Myelogenous Leukemia
- Chronic Eosinophilic Leukemia
- AIDS-related Peripheral/Systemic Lymphoma
- AIDS-related Primary CNS Lymphoma
- Extramedullary Plasmacytoma
- Isolated Plasmacytoma of Bone
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and dose-limiting toxicity of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction.
II. Determine the effects of hepatic dysfunction on the pharmacodynamics and pharmacokinetics of this drug in these patients.
III. Determine the non-dose-limiting toxic effects of this drug in these patients.
IV. Determine the response rate of these patients treated with this drug. V. Correlate the Childs-Pugh classification of hepatic dysfunction with observed toxic effects, pharmacodynamics, and pharmacokinetics of this drug in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to liver dysfunction (normal vs mild vs moderate vs severe).
Patients receive oral imatinib mesylate daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients within each stratum (except normal stratum) receive escalating doses of imatinib mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 1 year.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15232
- University of Pittsburgh
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Histologically or cytologically confirmed surgically incurable solid tumor orhematologic malignancy for which no standard or palliative therapy exists oris no longer effective
All tumor types are eligible, including:
- Chronic myelogenous leukemia or other Philadelphia chromosome-positive leukemia OR
- Gastrointestinal stromal tumors
- Patients with gliomas that require corticosteroids or anticonvulsants must beon a stable dose and seizure-free for 1 month
- No unstable or untreated (non-irradiated) brain metastases
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
- More than 3 months
- WBC at least 3,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- No active hemolysis
- See Surgery
- No evidence of biliary sepsis
- Creatinine normal
- Creatinine clearance at least 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Able to swallow pills
- No other uncontrolled concurrent illness that would preclude study participation
- No ongoing or active infection
- No uncontrolled diarrhea
- No psychiatric illness or social situation that would preclude study compliance
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for 6 months after study completion
- At least 24 hours since prior colony-stimulating factors
- No concurrent colony-stimulating factors
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- See Disease Characteristics
- See Disease Characteristics
- At least 4 weeks since prior radiotherapy and recovered
- See Disease Characteristics
- At least 10 days since prior placement of shunt for treatment of biliary obstruction
- At least 14 days since prior major surgery
- No prior solid organ transplantation
- No other concurrent investigational agents
- No concurrent therapeutic doses of warfarin for anticoagulation
- No other concurrent investigational or commercial agents or therapies for treatment of this disease
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent acetaminophen of more than 4,000 mg/day
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (imatinib mesylate)
Patients receive oral imatinib mesylate daily.
Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients within each stratum (except normal stratum) receive escalating doses of imatinib mesylate until the maximum tolerated dose (MTD) is determined.
The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity
|
Correlative studies
Other Names:
Given orally
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MTD defined based on the toxicities observed during the first cycle of treatment
Time Frame: 4 weeks
|
4 weeks
|
|
Toxicity evaluation graded according to the NCI common toxicity criteria and relationship to the study drug
Time Frame: Up to 4 years
|
Results will be tabulated by liver dysfunction group.
|
Up to 4 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetic data
Time Frame: Day 1, 2, 3, 4, 15, 16
|
Will be analyzed with ADAPT II, and results will be summarized separately for the four study groups.
Additionally, results for pharmacokinetic parameters will be related to the measured level of liver dysfunction in exploratory analyses.
|
Day 1, 2, 3, 4, 15, 16
|
Responses
Time Frame: Up to 4 years
|
Will be tabulated by liver dysfunction group, and by dose if appropriate.
|
Up to 4 years
|
Child-Pugh Classification
Time Frame: Baseline
|
Will be correlated to the toxicities, pharmacokinetic and pharmacodynamic data seen with STI571.
|
Baseline
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ramesh Ramanathan, University of Pittsburgh
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Metabolic Diseases
- Virus Diseases
- Infections
- Immune System Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Disease Attributes
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Blood Protein Disorders
- DNA Virus Infections
- Bacterial Infections and Mycoses
- Neoplastic Processes
- Proteostasis Deficiencies
- Tumor Virus Infections
- Neoplasms, Plasma Cell
- Blood Coagulation Disorders
- Blood Platelet Disorders
- Precancerous Conditions
- Leukocyte Disorders
- Epstein-Barr Virus Infections
- Herpesviridae Infections
- Leukemia, B-Cell
- Neoplasms, Connective Tissue
- Eosinophilia
- Cell Transformation, Neoplastic
- Carcinogenesis
- Hypergammaglobulinemia
- Eye Neoplasms
- Lymphadenopathy
- Bone Marrow Neoplasms
- Hematologic Neoplasms
- Liver Diseases
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Syndrome
- Myelodysplastic Syndromes
- Primary Myelofibrosis
- Multiple Myeloma
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Neoplasm Metastasis
- Hodgkin Disease
- Recurrence
- Lymphoma, Non-Hodgkin
- Immunoglobulin Light-chain Amyloidosis
- Amyloidosis
- Preleukemia
- Leukemia, Myelomonocytic, Chronic
- Leukemia, Myelomonocytic, Juvenile
- Mycoses
- Thrombocytosis
- Thrombocythemia, Essential
- Burkitt Lymphoma
- Lymphoma, Mantle-Cell
- Lymphoma, B-Cell, Marginal Zone
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Lymphoma, Large-Cell, Immunoblastic
- Plasmablastic Lymphoma
- Waldenstrom Macroglobulinemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Gastrointestinal Stromal Tumors
- Leukemia, Lymphoid
- Hypereosinophilic Syndrome
- Lymphoma, T-Cell
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Leukemia, Myeloid, Chronic-Phase
- Blast Crisis
- Lymphoma, T-Cell, Cutaneous
- Leukemia, T-Cell
- Leukemia-Lymphoma, Adult T-Cell
- Plasmacytoma
- Mycosis Fungoides
- Sezary Syndrome
- Lymphoma, Large-Cell, Anaplastic
- Leukemia, Myeloid, Accelerated Phase
- Intraocular Lymphoma
- Immunoblastic Lymphadenopathy
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia, Prolymphocytic
- Polycythemia Vera
- Polycythemia
- Paraproteinemias
- Monoclonal Gammopathy of Undetermined Significance
- Leukemia, Hairy Cell
- Leukemia, Large Granular Lymphocytic
- Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
- Leukemia, Neutrophilic, Chronic
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Imatinib Mesylate
Other Study ID Numbers
- NCI-2012-02418
- U01CA099168 (U.S. NIH Grant/Contract)
- U01CA062502 (U.S. NIH Grant/Contract)
- U01CA062505 (U.S. NIH Grant/Contract)
- U01CA062491 (U.S. NIH Grant/Contract)
- U01CA062487 (U.S. NIH Grant/Contract)
- 01-028
- CDR0000068959 (Registry Identifier: PDQ (Physician Data Query))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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