Clinical trial NCT00025415: Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction
Official title: A Phase I Pharmacokinetic Study of STI571 in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 60
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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 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

Primary outcomes:
measure: MTD defined based on the toxicities observed during the first cycle of treatment
timeFrame: 4 weeks
measure: Toxicity evaluation graded according to the NCI common toxicity criteria and relationship to the study drug
timeFrame: Up to 4 years
Secondary outcomes:
measure: Pharmacokinetic data
timeFrame: Day 1, 2, 3, 4, 15, 16
measure: Responses
timeFrame: Up to 4 years
measure: Child-Pugh Classification
timeFrame: Baseline
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Ramesh Ramanathan
role: PRINCIPAL_INVESTIGATOR
References: