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PS-341 in Treating Patients With Hematologic Cancer
This study has been completed.
First Received: August 3, 2000   Last Updated: November 16, 2008   History of Changes
Sponsors and Collaborators: Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00006098
  Purpose

RATIONALE: PS-341 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: Phase I trial to study the effectiveness of PS-341 in treating patients who have hematologic cancer.


Condition Intervention Phase
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Drug: bortezomib
Phase I

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma Multiple Myeloma
Drug Information available for: Bortezomib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Phase I Study of PS-341 in Patients With Hematologic Malignancies

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: April 2000
Detailed Description:

OBJECTIVES: I. Determine the maximum tolerated dose and dose-limiting toxicity of PS-341 in patients with hematologic malignancies. II. Determine the pharmacodynamics of this drug in these patients. III. Determine response to this drug in these patients. IV. Determine the correlation between response of malignancies and proteasome inhibition and apoptosis in peripheral blood mononuclear cells (PBMC) of these patients. V. Determine the correlation between therapy toxicity and proteasome inhibition and apoptosis in PBMC of these patients. VI. Determine the effect of this drug on other molecular markers (i.e., BCL-2 in follicular lymphoma patients and t9;22/BCR/ABL in chronic lymphocytic leukemia patients). VII. Determine the correlation between interleukin-6 serum levels in multiple myeloma patients and drug dosing, toxicity of therapy, extent of protease inhibition, response to therapy, and apoptosis in PBMC of these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients receive PS-341 IV over 30 minutes on days 1, 4, 8, 11, 15, 18, 22, and 25 followed by a 2-week rest. 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 at which 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Histologically confirmed hematologic malignancy including: Acute myeloid leukemia Chronic myelogenous leukemia Acute lymphoblastic leukemia Chronic lymphocytic leukemia Hodgkin's disease Non-Hodgkin's lymphoma Multiple myeloma Myelodysplastic syndrome subtypes: Refractory anemia with excess blasts (RAEB) RAEB in transformation Refractory to standard treatment or no curative therapy available Measurable disease Not eligible for higher priority study

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 6 weeks Hematopoietic: WBC at least 3,000/mm3 Absolute neutrophil count at least 1,000/mm3 Platelet count at least 50,000/mm3 Hematocrit at least 25% Hepatic: SGOT and SGPT less than 2.5 times upper limit of normal (ULN) Bilirubin less than 1.5 times ULN Renal: Creatinine clearance greater than 50 mL/min Cardiovascular: No acute ischemia or new conduction system abnormalities by EKG No prior myocardial infarction within past 6 months No New York Heart Association class III or IV congestive heart failure Other: Febrile episodes up to 38.5 degrees C due to tumor fever allowed No concurrent active infection No grade 1 or greater National Cancer Institute common toxicity criteria No serious medical or psychiatric condition that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior immunotherapy No concurrent immunotherapy Chemotherapy: At least 4 weeks since prior chemotherapy No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy No concurrent radiotherapy Surgery: At least 2 weeks since prior major surgery

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006098

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Steven Soignet, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000068105, MSKCC-00031, NCI-G00-1827
Study First Received: August 3, 2000
Last Updated: November 16, 2008
ClinicalTrials.gov Identifier: NCT00006098     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent adult Hodgkin lymphoma
refractory multiple myeloma
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
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
previously treated myelodysplastic syndromes
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma

Study placed in the following topic categories:
Lymphoma, Mantle-Cell
Mantle Cell Lymphoma
Follicular Lymphoma
Refractory Anemia
Preleukemia
Acute Myelocytic Leukemia
Anemia, Refractory
Hemorrhagic Disorders
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Blood Coagulation Disorders
Leukemia, Myeloid
Protease Inhibitors
Multiple Myeloma
B-cell Lymphomas
Chronic Myelogenous Leukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Hematologic Neoplasms
Precancerous Conditions
Blood Protein Disorders
Lymphoma, Follicular
Lymphoma, B-Cell, Marginal Zone
Paraproteinemias
Leukemia, Myeloid, Acute

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Antineoplastic Agents
Blood Protein Disorders
Paraproteinemias
Hemostatic Disorders
Leukemia
Preleukemia
Hemorrhagic Disorders
Pathologic Processes
Therapeutic Uses
Syndrome
Cardiovascular Diseases
Lymphoma
Immunoproliferative Disorders
Neoplasms by Histologic Type
Disease
Immune System Diseases
Hematologic Diseases
Myelodysplastic Syndromes
Bortezomib
Vascular Diseases
Enzyme Inhibitors
Pharmacologic Actions
Protease Inhibitors
Multiple Myeloma
Lymphatic Diseases
Neoplasms
Lymphoproliferative Disorders
Bone Marrow Diseases

ClinicalTrials.gov processed this record on May 06, 2009