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Sponsors and Collaborators: |
Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI) |
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Information provided by: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00006098 |
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 |
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Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes |
Drug: bortezomib |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | A Phase I Study of PS-341 in Patients With Hematologic Malignancies |
Study Start Date: | April 2000 |
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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
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
United States, New York | |
Memorial Sloan-Kettering Cancer Center | |
New York, New York, United States, 10021 |
Study Chair: | Steven Soignet, MD | Memorial Sloan-Kettering Cancer Center |
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 |
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 |
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 |
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 |