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PS-341 in Treating Patients With Refractory or Progressive Multiple Myeloma
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: Millennium Pharmaceuticals, Inc.
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00049478
  Purpose

RATIONALE: PS-341 may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. It is not yet known if PS-341 is effective in treating patients who have multiple myeloma.

PURPOSE: Randomized phase III trial to study the effectiveness of PS-341 in treating patients who have refractory or progressive multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: bortezomib
Drug: dexamethasone
Phase III

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Cancer Multiple Myeloma
Drug Information available for: Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Bortezomib
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: An International, Non-Comparative, Open-Label Study of PS-341 Administered to Patients With Multiple Myeloma Who Experienced Relapsed or Progressive Disease After Receiving at Least Four Previous Treatment Regimens or Experienced Progressive Disease After Receiving Dexamethasone in FHCRC Protocol 1746.00

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

Study Start Date: July 2002
Detailed Description:

OBJECTIVES:

  • Determine the time to progressive disease in patients with refractory or progressive multiple myeloma treated with PS-341.
  • Determine the safety and tolerability of this drug in these patients.
  • Determine survival of patients treated with this drug.
  • Determine the rate and duration of response (complete and partial) in patients treated with this drug.
  • Assess the relationship between selected genetic disease markers and response in patients treated with this drug.

OUTLINE: This is an open-label, multicenter study.

  • Induction therapy: Patients receive PS-341 IV on days 1, 4, 8, and 11. Treatment repeats every 3 weeks for up to 8 courses.
  • Maintenance therapy: Patients receive PS-341 IV on days 1, 8, 15, and 22. Treatment repeats every 5 weeks for up to 3 courses.

Patients who experience progressive disease (PD) after at least 2 courses or no change after at least 4 courses may also receive oral dexamethasone on the day of and the day after PS-341 administration. Patients who experience PD after at least 2 courses of this combined therapy go off study.

Patients are followed at 30 days, every 6 weeks until disease progression, and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study within 1 year.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma (MM) and meeting 1 of the following criteria:

    • Progressive disease during or after treatment with high-dose dexamethasone on MPI Study M34101-039 (FHCRC-1746.00), with no other antineoplastic treatment for MM initiated
    • Relapsed or progressive disease after receiving at least 4 prior treatment regimens for MM (non-MPI patients)

PATIENT CHARACTERISTICS:

Age

  • Adult

Performance status

  • Karnofsky 60-100% (non-MPI patients)

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count at least 500/mm^3 (no growth factor support)
  • Platelet count at least 20,000/mm^3 (transfusions allowed)
  • Hemoglobin at least 7.0 g/dL (transfusions allowed)

Hepatic

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • AST and ALT no greater than 2.5 times ULN
  • Hepatitis B surface antigen negative
  • No known active hepatitis C infection

Renal

  • Calcium less than 14 mg/dL
  • Creatinine clearance at least 20 mL/min

Cardiovascular

  • Non-MPI patients:

    • No myocardial infarction within the past 6 months
    • No New York Heart Association class III or IV heart failure
    • No uncontrolled angina
    • No severe uncontrolled ventricular arrhythmias
    • No acute ischemia or active conduction system abnormalities by EKG
    • No cardiac amyloidosis
    • No poorly controlled hypertension

Other

  • All patients:

    • Not pregnant or nursing
    • Negative pregnancy test
    • Fertile patients must use effective contraception
    • HIV negative
  • Non-MPI patients:

    • No other serious medical or psychiatric illness that would preclude study
    • No prior allergic reaction attributable to compounds containing boron or mannitol
    • No peripheral neuropathy grade 2 or greater
    • No diabetes mellitus
    • No active systemic infection requiring treatment
  • MPI patients:

    • Recovered from dexamethasone-related toxicity
    • No other new or worsening existing illness that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • At least 4 weeks since prior immunotherapy or antibody therapy (non-MPI patients)
  • No concurrent thalidomide

Chemotherapy

  • At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) (non-MPI patients)

Endocrine therapy

  • See Disease Characteristics
  • At least 3 weeks since prior corticosteroids (greater than 10 mg/day of prednisone or equivalent) (non-MPI patients)
  • No other concurrent corticosteroids (e.g., greater than 10 mg/day of prednisone or equivalent)

Radiotherapy

  • Concurrent local short-duration radiotherapy allowed

Surgery

  • At least 4 weeks since prior major surgery (except kyphoplasty) (non-MPI patients)
  • Concurrent kyphoplasty allowed
  • Concurrent emergency orthopedic procedures allowed

Other

  • No other concurrent antineoplastic treatment for MM
  • No other concurrent investigational agents, including commercial agents approved for other indications but investigational for MM
  • No concurrent clarithromycin
  • Concurrent bisphosphonates allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00049478

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Chair: Denise Collins Millennium Pharmaceuticals, Inc.
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000258110, MILLENNIUM-M34101-040, FHCRC-1747.00, NCI-G02-2128
Study First Received: November 12, 2002
Last Updated: November 16, 2008
ClinicalTrials.gov Identifier: NCT00049478  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
refractory multiple myeloma

Study placed in the following topic categories:
Dexamethasone
Immunoproliferative Disorders
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Bortezomib
Vascular Diseases
Paraproteinemias
Hemostatic Disorders
Multiple Myeloma
Hemorrhagic Disorders
Multiple myeloma
Lymphoproliferative Disorders
Dexamethasone acetate
Neoplasms, Plasma Cell

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Immune System Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Antiemetics
Enzyme Inhibitors
Hormones
Glucocorticoids
Pharmacologic Actions
Protease Inhibitors
Neoplasms
Autonomic Agents
Therapeutic Uses
Cardiovascular Diseases
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 15, 2009