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Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction

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ClinicalTrials.gov Identifier: NCT00025415
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : February 7, 2013
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
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Brief Summary:
Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of imatinib mesylate in treating patients who have advanced cancer and liver dysfunction

Condition or disease Intervention/treatment Phase
Accelerated Phase Chronic Myelogenous Leukemia Acute Undifferentiated Leukemia AIDS-related Peripheral/Systemic Lymphoma AIDS-related Primary CNS Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Blastic Phase Chronic Myelogenous Leukemia Childhood Myelodysplastic Syndromes Chronic Eosinophilic Leukemia Chronic Myelogenous Leukemia, BCR-ABL1 Positive Chronic Myelomonocytic Leukemia Chronic Neutrophilic Leukemia Chronic Phase Chronic Myelogenous Leukemia de Novo Myelodysplastic Syndromes Essential Thrombocythemia Extramedullary Plasmacytoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Gastrointestinal Stromal Tumor Intraocular Lymphoma Isolated Plasmacytoma of Bone Meningeal Chronic Myelogenous Leukemia Monoclonal Gammopathy of Undetermined Significance Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Nodal Marginal Zone B-cell Lymphoma Polycythemia Vera Previously Treated Myelodysplastic Syndromes Primary Central Nervous System Non-Hodgkin Lymphoma Primary Myelofibrosis Primary Systemic Amyloidosis Progressive Hairy Cell Leukemia, Initial Treatment Prolymphocytic Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia 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 Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Hairy Cell Leukemia Refractory Multiple Myeloma Relapsing Chronic Myelogenous Leukemia Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Small Intestine Lymphoma Splenic Marginal Zone Lymphoma 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 Immunoblastic Large Cell Lymphoma Stage IV Adult Lymphoblastic Lymphoma Stage IV Adult T-cell Leukemia/Lymphoma Stage IV Chronic Lymphocytic Leukemia 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 T-cell Large Granular Lymphocyte Leukemia Unspecified Adult Solid Tumor, Protocol Specific Untreated Adult Acute Lymphoblastic Leukemia Untreated Adult Acute Myeloid Leukemia Untreated Hairy Cell Leukemia Waldenström Macroglobulinemia Drug: imatinib mesylate Other: pharmacological study Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Pharmacokinetic Study of STI571 in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction
Study Start Date : August 2001
Actual Primary Completion Date : January 2005

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Burkitt Lymphoma Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic Syndromes Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Lymphosarcoma Multiple Myeloma Hairy Cell Leukemia Follicular Lymphoma B-cell Lymphoma Mantle Cell Lymphoma Diffuse Large B-Cell Lymphoma Hodgkin Lymphoma AL Amyloidosis Marginal Zone Lymphoma Waldenstrom Macroglobulinemia Primary Central Nervous System Lymphoma Chronic Myelomonocytic Leukemia Juvenile Myelomonocytic Leukemia Gastrointestinal Stromal Tumors Cutaneous T-cell Lymphoma Chronic Myeloid Leukemia Myelofibrosis Chronic Myeloproliferative Disorders Mycosis Fungoides Lymphoma, Large-cell Anaplastic Large Cell Lymphoma Polycythemia Vera Essential Thrombocythemia Myelodysplastic/myeloproliferative Disease Sezary Syndrome Lymphoblastic Lymphoma Monoclonal Gammopathy of Undetermined Significance Plasmacytoma Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Leukemia, T-cell, Chronic Adult T-cell Leukemia/lymphoma Large Granular Lymphocyte Leukemia Aggressive NK Cell Leukemia Plasmablastic Lymphoma Lymphoma, Large-cell, Immunoblastic Chronic Neutrophilic Leukemia Hypereosinophilic Syndrome
U.S. FDA Resources

Arms and Interventions
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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
 Drug: imatinib mesylate
Given orally
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies


Outcome Measures
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Primary Outcome Measures :
  1. MTD defined based on the toxicities observed during the first cycle of treatment [ Time Frame: 4 weeks ]
  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. Responses [ Time Frame: Up to 4 years ]
    Will be tabulated by liver dysfunction group, and by dose if appropriate.

  3. Child-Pugh Classification [ Time Frame: Baseline ]
    Will be correlated to the toxicities, pharmacokinetic and pharmacodynamic data seen with STI571.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00025415


Locations
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ramesh Ramanathan University of Pittsburgh
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00025415     History of Changes
Obsolete Identifiers: NCT00025948
Other Study ID Numbers: NCI-2012-02418
01-028
U01CA099168 ( U.S. NIH Grant/Contract )
U01CA062505 ( U.S. NIH Grant/Contract )
U01CA062491 ( U.S. NIH Grant/Contract )
U01CA062502 ( U.S. NIH Grant/Contract )
U01CA062487 ( U.S. NIH Grant/Contract )
CDR0000068959 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: February 7, 2013
Last Verified: February 2013

Additional relevant MeSH terms:
Lymphoma
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Multiple Myeloma
Lymphoma, Follicular
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Neoplasm Metastasis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
 Hodgkin Disease
Lymphoma, Mantle-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Burkitt Lymphoma
Lymphoma, T-Cell
Lymphoma, Large-Cell, Immunoblastic
Plasmablastic Lymphoma
Mycoses
Primary Myelofibrosis
Mycosis Fungoides
Sezary Syndrome
Lymphoma, T-Cell, Cutaneous
Leukemia, T-Cell