A Phase I and Pharmacologic Study of the Proteasome Inhibitor PS-341 in Patients With Advanced Solid Tumors and B-cell Lymphoproliferative Disorders
18 Years
N/A
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Precancerous Condition, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I and Pharmacologic Study of the Proteasome Inhibitor PS-341 in Patients With Advanced Solid Tumors and B-cell Lymphoproliferative Disorders
OBJECTIVES:
- Determine the maximum tolerated dose and toxicity of PS-341 in patients with advanced
malignancies.
- Determine, in a preliminary manner, the therapeutic activity of this regimen in these
patients.
OUTLINE: This is a dose-escalation, multicenter study.
- Regimen A: Patients receive PS-341 IV twice weekly for 4 weeks. Treatment repeats every
6 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of PS-341 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3-4 or 2 of
6 patients experience dose-limiting toxicity.
- Regimen B: Once the MTD has been determined in regimen A, patients receive PS-341 IV
twice weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease
progression or unacceptable toxicity.
Patients are followed for 3 months.
PROJECTED ACCRUAL: A maximum of 78 patients will be accrued for this study within 14 months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically proven advanced malignancy, including non-Hodgkin's lymphoma (NHL),
for which there is no known standard therapy that is potentially curative or
definitely capable of extending life expectancy
- Patients with B-cell lymphoproliferative disorders and a leukemic phase are
eligible once the maximum tolerated dose is established
- NHL patients must meet the following conditions:
- No greater than 25% of bone marrow involved
- No symptomatic brain metastases
- Prior brain metastases allowed if definitively treated (radiotherapy and/or
surgery) and stable for at least 8 weeks
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- ECOG 0-2
Life expectancy:
- At least 12 weeks
Hematopoietic:
- Absolute neutrophil count at least 1,500/mm3
- Platelet count at least 100,000/mm3
Hepatic:
- Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- AST or ALT no greater than 2.5 times ULN (5 times ULN if liver involvement)
Renal:
- Creatinine no greater than 1.5 times ULN
Cardiovascular:
- No New York Heart Association class III or IV heart disease
Other:
- No uncontrolled infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 4 weeks since prior biologic therapy or immunotherapy
- No concurrent immunotherapy
Chemotherapy:
- At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and
recovered
- No other concurrent chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- See Disease Characteristics
- No prior radiotherapy to greater than 30% of bone marrow
- At least 4 weeks since prior radiotherapy
- No concurrent radiotherapy
Surgery:
- See Disease Characteristics
Other:
- No concurrent antiretroviral therapy (HAART) for HIV positive patients
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Alex A. Adjei, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Federal Government
Study ID:
CDR0000068233
NCT ID:
NCT00006362
Start Date:
November 1999
Completion Date:
August 2003
Related Keywords:
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Precancerous Condition
- Unspecified Adult Solid Tumor, Protocol Specific
- monoclonal gammopathy of undetermined significance
- isolated plasmacytoma of bone
- extramedullary plasmacytoma
- refractory multiple myeloma
- Waldenstrom macroglobulinemia
- stage III multiple myeloma
- stage IV chronic lymphocytic leukemia
- refractory chronic lymphocytic leukemia
- unspecified adult solid tumor, protocol specific
- B-cell chronic lymphocytic leukemia
- untreated hairy cell leukemia
- progressive hairy cell leukemia, initial treatment
- refractory hairy cell leukemia
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV adult Burkitt lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent adult Burkitt lymphoma
- primary systemic amyloidosis
- stage IV mantle cell lymphoma
- recurrent mantle cell lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- stage IV small lymphocytic lymphoma
- stage IV marginal zone lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- Neoplasms
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Lymphoproliferative Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Precancerous Conditions
- Lymphoma, Large-Cell, Immunoblastic
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
| University of Wisconsin Comprehensive Cancer Center | Madison, Wisconsin 53792 |
