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PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome
This study has been completed.
First Received: April 6, 2000   Last Updated: July 23, 2008   History of Changes
Sponsors and Collaborators: M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005064
  Purpose

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

PURPOSE: Phase I trial to study the effectiveness of PS-341 in treating patients who have refractory or relapsed acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia in blast phase, or myelodysplastic syndrome.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Drug: bortezomib
Phase I

Study Type: Interventional
Study Design: Treatment
Official Title: Phase I Study of PS-341 in Acute Myeloid Leukemias, Myelodysplastic Syndromes and Chronic Myeloid Leukemia in Blast Phase

Resource links provided by NLM:


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

Study Start Date: February 2000
Detailed Description:

OBJECTIVES: I. Determine the maximum tolerated dose of PS-341 in patients with refractory or relapsed acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia in blast phase. II. Assess the plasma pharmacology of this drug, its ability to inhibit proteasome function and to accelerate apoptosis in circulating blasts in this patient population. III. Assess the antileukemic effects of this drug in these patients.

OUTLINE: This is a dose-escalation study. Patients receive PS-341 IV bolus twice weekly for 4 weeks followed by 2 weeks of rest. Treatment continues for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression. Cohorts of 2 patients receive escalating doses of PS-341 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose level associated with toxicity probability closest to 0.2 after 30 patients are treated.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 10 months.

  Eligibility

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

DISEASE CHARACTERISTICS: Acute myeloid leukemia, acute lymphoblastic leukemia, or high-risk myelodysplastic syndrome (i.e., refractory anemia with excess blasts (RAEB) or RAEB in transformation) that has: Not responded (no complete remission (CR)) to initial induction chemotherapy OR Recurred after an initial CR of less than 1 year OR Recurred after an initial CR of greater than 1 year and failed to respond to an initial reinduction attempt OR Recurred more than once OR Chronic myeloid leukemia in blast phase previously untreated for blast phase or that has failed other treatments for blast phase Refractory or relapsed acute promyelocytic leukemia eligible provided failed a prior tretinoin containing regimen Not likely to benefit from allogeneic bone marrow transplantation (i.e., less than 60 years of physiological age with histocompatible donor) No known brain metastases or CNS disease

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 OR Karnofsky 50-100% Life expectancy:

Not specified Hematopoietic: Not specified Hepatic: Bilirubin less than 1.6 mg/dL ALT or AST no greater than 2.5 times upper limit of normal Renal: Creatinine less than 1.6 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia Other: Not pregnant or nursing Fertile patients must use effective contraception No other concurrent uncontrolled illness (e.g., ongoing or active infection)

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 2 weeks since prior chemotherapy and recovered At least 24 hours since prior hydroxyurea for rapidly proliferative disease (i.e., absolute peripheral blood blast count at least 5,000/mm3 and increasing by at least 1,000/mm3/24 hours) Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: No other concurrent investigational agents No concurrent antiretroviral therapy (HAART) for HIV positive patients

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005064

Locations
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Jorge Cortes, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000067668, MDA-DM-99245, NCI-94
Study First Received: April 6, 2000
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00005064     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
adult acute promyelocytic leukemia (M3)
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
previously treated myelodysplastic syndromes

Study placed in the following topic categories:
Blast Crisis
Leukemia, Lymphoid
Precancerous Conditions
Leukemia, Myeloid, Acute
Refractory Anemia
Leukemia
Acute Myelocytic Leukemia
Preleukemia
Anemia, Refractory
Acute Myeloid Leukemia, Adult
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Promyelocytic, Acute
Lymphoma
Acute Lymphoblastic Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Bortezomib
Myelodysplastic Syndromes
Anemia
Myeloproliferative Disorders
Leukemia, Myeloid
Recurrence
Protease Inhibitors
Lymphatic Diseases
Chronic Lymphocytic Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Anemia, Refractory, with Excess of Blasts
Chronic Myelogenous Leukemia
Bone Marrow Diseases

Additional relevant MeSH terms:
Blast Crisis
Leukemia, Lymphoid
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Antineoplastic Agents
Leukemia, Myeloid, Acute
Leukemia
Preleukemia
Neoplastic Processes
Pathologic Processes
Leukemia, Lymphocytic, Chronic, B-Cell
Therapeutic Uses
Syndrome
Disease
Neoplasms by Histologic Type
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases
Bortezomib
Myelodysplastic Syndromes
Myeloproliferative Disorders
Enzyme Inhibitors
Leukemia, Myeloid
Pharmacologic Actions
Protease Inhibitors
Lymphatic Diseases
Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Bone Marrow Diseases

ClinicalTrials.gov processed this record on September 03, 2009