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A Phase I and Pharmacologic Study of the Proteasome Inhibitor PS-341 in Patients With Advanced Solid Tumors and B-cell Lymphoproliferative Disorders


Phase 1
18 Years
N/A
Not Enrolling
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Precancerous Condition, Unspecified Adult Solid Tumor, Protocol Specific

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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 ClinicRochester, Minnesota  55905
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792