Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

AIDS-related Peripheral/Systemic Lymphoma

Stage IV Small Lymphocytic Lymphoma

Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Polycythemia Vera

Stage IV Marginal Zone Lymphoma

Chronic Neutrophilic Leukemia

T-cell Large Granular Lymphocyte Leukemia

Stage IV Adult Diffuse Small Cleaved Cell Lymphoma

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue

Chronic Eosinophilic Leukemia

Splenic Marginal Zone Lymphoma

Recurrent Adult Diffuse Small Cleaved Cell Lymphoma

Recurrent Grade 3 Follicular Lymphoma

Recurrent Marginal Zone Lymphoma

Childhood Myelodysplastic Syndromes

Monoclonal Gammopathy of Undetermined Significance

Progressive Hairy Cell Leukemia, Initial Treatment

Small Intestine Lymphoma

Recurrent Grade 1 Follicular Lymphoma

Stage IV Adult Lymphoblastic Lymphoma

Recurrent Mantle Cell Lymphoma

Blastic Phase Chronic Myelogenous Leukemia

Angioimmunoblastic T-cell Lymphoma

Essential Thrombocythemia

Primary Systemic Amyloidosis

Chronic Myelomonocytic Leukemia

Waldenström Macroglobulinemia

Recurrent Small Lymphocytic Lymphoma

Untreated Adult Acute Lymphoblastic Leukemia

Recurrent Grade 2 Follicular Lymphoma

AIDS-related Primary CNS Lymphoma

Accelerated Phase Chronic Myelogenous Leukemia

Nodal Marginal Zone B-cell Lymphoma

Recurrent Adult Burkitt Lymphoma

Recurrent Mycosis Fungoides/Sezary Syndrome

Chronic Phase Chronic Myelogenous Leukemia

Refractory Hairy Cell Leukemia

Untreated Hairy Cell Leukemia

Recurrent Adult Hodgkin Lymphoma

Untreated Adult Acute Myeloid Leukemia

Stage IV Grade 2 Follicular Lymphoma

Refractory Multiple Myeloma

Stage IV Adult Diffuse Mixed Cell Lymphoma

Stage IV Adult T-cell Leukemia/Lymphoma

Previously Treated Myelodysplastic Syndromes

Gastrointestinal Stromal Tumor

Anaplastic Large Cell Lymphoma

Isolated Plasmacytoma of Bone

Relapsing Chronic Myelogenous Leukemia

Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma

Recurrent Adult Diffuse Mixed Cell Lymphoma

Stage IV Adult Hodgkin Lymphoma

Refractory Chronic Lymphocytic Leukemia

Recurrent Adult Immunoblastic Large Cell Lymphoma

Recurrent Adult Acute Lymphoblastic Leukemia

Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative

Stage IV Grade 3 Follicular Lymphoma

Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma

Recurrent Adult Lymphoblastic Lymphoma

Stage IV Mycosis Fungoides/Sezary Syndrome

Prolymphocytic Leukemia

Intraocular Lymphoma

Stage IV Adult Diffuse Large Cell Lymphoma

Unspecified Adult Solid Tumor, Protocol Specific

de Novo Myelodysplastic Syndromes

Meningeal Chronic Myelogenous Leukemia

Stage IV Adult Immunoblastic Large Cell Lymphoma

Recurrent Adult Diffuse Large Cell Lymphoma

Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

Secondary Myelodysplastic Syndromes

Stage IV Adult Burkitt Lymphoma

Stage IV Mantle Cell Lymphoma

Extramedullary Plasmacytoma

Stage IV Chronic Lymphocytic Leukemia

Primary Myelofibrosis

Secondary Acute Myeloid Leukemia

Recurrent Adult Acute Myeloid Leukemia

Acute Undifferentiated Leukemia

Primary Central Nervous System Non-Hodgkin Lymphoma

Recurrent Adult T-cell Leukemia/Lymphoma

Stage IV Grade 1 Follicular Lymphoma

Treatments

Drug: imatinib mesylate

Other: pharmacological study

Study type

Interventional

Funder types

NIH

Identifiers

NCT00025415

01-028

U01CA062502 (U.S. NIH Grant/Contract)

U01CA062505 (U.S. NIH Grant/Contract)

NCI-2012-02418

U01CA062487 (U.S. NIH Grant/Contract)

U01CA099168 (U.S. NIH Grant/Contract)

U01CA062491 (U.S. NIH Grant/Contract)

CDR0000068959 (Registry Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment

60 patients

Sex

All

Ages

15+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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