Clinical trial NCT00389701: Bortezomib and Dexamethasone in Treating Patients With Multiple Myeloma That Has Relapsed or Has Not Responded to Treatment
Official title: Phase II Trial of Twice Weekly Induction Followed by Once Weekly IV Velcade (Bortezomib) With Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma Following at Least 1 Prior Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-10-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with dexamethasone may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with dexamethasone works in treating patients with multiple myeloma that has relapsed or has not responded to treatment.

Detailed description: OBJECTIVES:

Primary

* Determine the overall response rate (complete response and partial response) in patients with relapsed or refractory multiple myeloma treated with induction therapy and maintenance therapy comprising bortezomib and dexamethasone.

Secondary

* Determine the toxicity of this regimen in these patients
* Determine the tolerability of this regimen in these patients.
* Determine the duration of response in patients treated with this regimen.
* Determine time to progression in patients treated with this regimen.
* Determine overall and progression-free survival of patients treated with this regimen.

OUTLINE: This is an open-label study.

* Induction therapy: Patients receive bortezomib IV on days 1, 4, 8, and 11. Patients also receive oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 4 courses. Patients who achieve complete response (CR) receive an additional 2 courses of induction therapy and proceed to maintenance therapy.
* Maintenance therapy: Patients receive bortezomib IV on days 1, 8, 15, and 22. Patients also receive oral dexamethasone on days 1, 2, 8, 9, 15, 16, 22, and 23. Treatment repeats every 36 days in the absence of disease progression or unacceptable toxicity. Patients who achieve CR receive an additional 2 courses of maintenance therapy beyond documentation of CR.

After completion of study treatment, patients are followed every 3 months.

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

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of multiple myeloma

  * Refractory or relapsed disease meeting the following criteria:

    * Primary refractory disease and first-line relapsing disease
    * Progressive disease after last therapy

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy \> 3 months
* Platelet count ≥ 50,000/mm³ (≥ 30,000/mm³ for patients with significant bone marrow involvement)

  * Transfusions allowed
* Hemoglobin ≥ 7.5 g/dL
* Absolute neutrophil count ≥ 750/mm³
* Serum calcium \< 14 mg/dL
* AST and ALT \< 2.5 times upper limit of normal
* Creatinine clearance ≥ 30 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No peripheral neuropathy ≥ grade 2 within the past 14 days
* No hypersensitivity to boron or mannitol
* No cardiovascular complications, including any of the following:

  * Myocardial infarction within the past 6 months
  * New York Heart Association class III-IV heart failure
  * Uncontrolled angina
  * Ventricular arrhythmias
  * Electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  * Cardiac amyloidosis
* No other cancer or treatment for cancer other than basal cell cancer of the skin within the past 5 years
* No poorly controlled chronic diseases (e.g., diabetes mellitus or hypertension)
* No HIV positivity
* No hepatitis B surface antigen or active hepatitis C infection
* No active systemic infection requiring therapy
* No serious medical or psychiatric illness that would interfere with study participation

PRIOR CONCURRENT THERAPY:

* No plasmapheresis within the past 4 weeks
* No major surgery within the past 4 weeks
* No prior bortezomib
* No chemotherapy (e.g., clarithromycin) within the past 4 weeks
* No radiotherapy within the past 3 weeks
* No corticosteroids (\> 10 mg/day of prednisone or equivalent) within the past 3 weeks
* No other immunotherapy within the past 8 weeks
* No other investigational drugs within the past 14 days
* No concurrent participation in other clinical research studies

Primary outcomes:
measure: Overall response rate
Secondary outcomes:
measure: Toxicity
measure: Tolerability
measure: Duration of response after completion of treatment
measure: Time to progression
measure: Overall and progression-free survival
Other outcomes:
Locations:
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
Study officials:
affiliation: Sparrow Regional Cancer Center
name: Gordan Srkalovic, MD, PhD
role: STUDY_CHAIR
References: