Clinical trial NCT00288028: Bortezomib in Treating Patients With Multiple Myeloma Who Have Undergone an Autologous Peripheral Blood Stem Cell Transplant
Official title: A Phase I Study of Bortezomib During Maintenance Phase After High Dose Melphalan and Autologous Stem Cell Transplantation in Patients With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-02-07
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib after an autologous peripheral blood stem cell transplant may stop the growth of any cancer cells that remain after transplant.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib in treating patients with multiple myeloma who have undergone an autologous peripheral blood stem cell transplant.

Detailed description: OBJECTIVES:

Primary

* Determine the maximum tolerated dose (MTD) of bortezomib during maintenance phase after high-dose melphalan and autologous peripheral blood stem cell transplantation in patients with multiple myeloma.
* Determine the safety and tolerability of bortezomib in these patients.

Secondary

* Determine the overall response rate, complete response rate, and response duration in patients treated with bortezomib at the MTD.

OUTLINE: This is an open-label, dose-finding study.

Patients receive bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 21 or 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive de-escalating doses of bortezomib (at varying dosing schedules) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

After completion of study treatment, patients are followed at 1 year.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of multiple myeloma
* Must have completed high-dose melphalan and autologous peripheral blood stem cell transplantation

  * Transplant must have been completed 30-120 days ago
  * Must not be receiving maintenance therapy
  * Patients must have received 200 mg/m² of melphalan intravenously as a conditioning regimen (no dose reduction allowed)
* No evidence of amyloidosis
* No available donor

PATIENT CHARACTERISTICS:

* ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
* Absolute neutrophil count \> 1,500/mm\^3
* Platelet count \> 75,000/mm\^3
* Bilirubin ≤ 1.5 times upper limit of normal
* Transaminase ≤ 3 times upper limit of normal
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Must have a negative HIV test
* No baseline neurological disease \> grade I
* No cranial nerve palsy
* No demonstrated resistance to bortezomib
* No history of allergic reactions attributed to bortezomib, boron, or mannitol
* No cardiac arrhythmia
* No unstable angina pectoris
* No symptomatic congestive heart failure
* No ongoing or active infection
* No other uncontrolled illness
* No psychiatric illness or social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No other concurrent anticancer therapies or agents
* No other concurrent investigational agents
* Not receiving maintenance therapy after prior stem cell transplantation on another clinical trial

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: At course 8
measure: Safety and tolerability
timeFrame: At course 8
Secondary outcomes:
measure: Overall response rate by Southwest Oncology Group (SWOG) criteria
timeFrame: At day 30 following stem cell transplant and following course 4, course 8, and 1 year of study treatment
measure: Complete response rate by SWOG criteria
timeFrame: At day 30 following stem cell transplant and following course 4, course 8, and 1 year of study treatment
measure: Response duration by SWOG criteria
timeFrame: At day 30 following stem cell transplant and following course 4, course 8, and 1 year of study treatment
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Muneer H. Abidi, MD
role: STUDY_CHAIR
References: