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A Phase I Pharmacokinetic Study of STI571 in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction


Phase 1
15 Years
N/A
Not Enrolling
Both
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

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Trial Information

A Phase I Pharmacokinetic Study of STI571 in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD defined based on the toxicities observed during the first cycle of treatment

Outcome Time Frame:

4 weeks

Safety Issue:

Yes

Principal Investigator

Ramesh Ramanathan

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02418

NCT ID:

NCT00025415

Start Date:

August 2001

Completion Date:

Related Keywords:

  • 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
  • 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, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Waldenstrom Macroglobulinemia
  • Monoclonal Gammopathy of Undetermined Significance
  • Paraproteinemias
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Mycoses
  • Mycosis Fungoides
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute
  • Myeloproliferative Disorders
  • Plasmacytoma
  • Polycythemia
  • Polycythemia Vera
  • Sezary Syndrome
  • Thrombocythemia, Essential
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Liver Diseases
  • Hypereosinophilic Syndrome
  • Lymphoma, Large-Cell, Anaplastic
  • Gastrointestinal Stromal Tumors
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Mantle-Cell
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
  • Thrombocytosis
  • Myelodysplastic-Myeloproliferative Diseases
  • Leukemia, Large Granular Lymphocytic

Name

Location

University of PittsburghPittsburgh, Pennsylvania  15261