Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction - Full Text View

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:

Genetics Home Reference related topics: PDGFRA-associated chronic eosinophilic leukemia PDGFRB-associated chronic eosinophilic leukemia Sézary syndrome Waldenström macroglobulinemia core binding factor acute myeloid leukemia cytogenetically normal acute myeloid leukemia essential thrombocythemia familial acute myeloid leukemia with mutated CEBPA gastrointestinal stromal tumor multiple myeloma mycosis fungoides polycythemia vera primary myelofibrosis

MedlinePlus related topics: Cancer Chronic Myeloid Leukemia Fungal Infections Leukemia Myelodysplastic Syndromes

Drug Information available for: Imatinib Imatinib mesylate

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

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

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 (Child, Adult, Senior)
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

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Ramesh Ramanathan	University of Pittsburgh

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 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:


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

ClinicalTrials.gov processed this record on September 23, 2016