Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00025415
First received: October 11, 2001
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD defined based on the toxicities observed during the first cycle of treatment [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • Toxicity evaluation graded according to the NCI common toxicity criteria and relationship to the study drug [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Results will be tabulated by liver dysfunction group.


Secondary Outcome Measures:
  • Pharmacokinetic data [ Time Frame: Day 1, 2, 3, 4, 15, 16 ] [ Designated as safety issue: No ]
    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.

  • Responses [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Will be tabulated by liver dysfunction group, and by dose if appropriate.

  • Child-Pugh Classification [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Will be correlated to the toxicities, pharmacokinetic and pharmacodynamic data seen with STI571.


Enrollment: 60
Study Start Date: August 2001
Primary Completion Date: January 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00025415

Locations
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Investigators
Principal Investigator: Ramesh Ramanathan University of Pittsburgh
  More Information

No publications provided

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, U01CA062505, U01CA062491, U01CA062502, U01CA062487, CDR0000068959
Study First Received: October 11, 2001
Last Updated: February 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Primary Myelofibrosis
Amyloidosis
Blast Crisis
Burkitt Lymphoma
Neoplasms
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Hairy Cell
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myelomonocytic, Chronic
Leukemia, Neutrophilic, Chronic
Leukemia, Prolymphocytic
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Waldenstrom Macroglobulinemia
Monoclonal Gammopathy of Undetermined Significance
Paraproteinemias
Multiple Myeloma

ClinicalTrials.gov processed this record on July 20, 2014