Clinical trial NCT00523848: Bortezomib, Doxorubicin Hydrochloride Liposome, and Thalidomide as First-line Therapy in Treating Patients With Previously Untreated Stage I, II, or III Multiple Myeloma
Official title: Phase II Study of VDT (VELCADE, Doxil® and Thalidomide) as Frontline Therapy for Patients With Previously Untreated Multiple Myeloma (MM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma and Plasma Cell Neoplasm
Keywords: stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
First posted: 2007-09-03
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
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. Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Thalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Giving bortezomib together with doxorubicin hydrochloride liposome and thalidomide may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib together with doxorubicin hydrochloride liposome and thalidomide works as first-line therapy in treating patients with previously untreated multiple myeloma.

Detailed description: OBJECTIVES:

Primary

* To determine the overall response rate (complete response and partial response) in patients previously untreated stage I, II, or III multiple myeloma.

Secondary

* To evaluate the complete response rate in patients treated with this regimen.
* To determine the time to disease progression from the start of this therapy in patients treated with this regimen.

OUTLINE: Patients receive low-dose oral thalidomide once a day on days 1-28, bortezomib IV on days 1, 4, 15, and 18, and doxorubicin hydrochloride liposome IV over 60-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with residual disease who continue to show response after completion of 6 courses may receive 2 additional courses for a total of 8 courses.

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

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of stage I, II, or III multiple myeloma requiring therapy
* No prior systemic therapy for multiple myeloma

  * Patients who have received steroids or radiotherapy for cord compression or spinal cord disease are eligible for this study
  * Patients who have received 1 prior course of antimyeloma therapy may be enrolled at the investigator's discretion provided disease progression is not noted

PATIENT CHARACTERISTICS:

Inclusion criteria:

* Karnofsky performance status 60-100%
* Platelet count ≥ 75,000 cells/mm\^3 (\< 75,000 cells/mm\^3 secondary to extensive bone marrow disease allowed at the PI's discretion with appropriate transfusion support)
* ANC ≥ 1,000 cells/mm\^3
* Hemoglobin ≥ 8.0 g/dL (\< 8 g/dL secondary to extensive bone marrow disease allowed at the PI's discretion with appropriate transfusion support)
* Creatinine clearance \> 20 mL/min
* AST and ALT ≤ 2 times upper limit of normal (ULN) OR ≤ 3 times ULN (in the presence of liver metastases)
* Alkaline phosphatase ≤ 2 times ULN OR ≤ 3 times ULN (in the presence of liver metastases)
* Total bilirubin ≤ 2 times ULN OR ≤ 3 times ULN (in the presence of liver metastases)
* Ejection fraction ≥ 50% by MUGA or 2-D echocardiogram
* Negative pregnancy test
* Fertile patients must use at least 1 highly effective and 1 additional effective contraception method 4 weeks prior to, during, and 3 months after completion of study therapy
* HIV-negative
* Must have sufficient mental capacity to understand the explanation of the study and to provide informed consent
* Willingness and ability to comply with the FDA-mandated S.T.E.P.S. program

Exclusion criteria:

* Pregnant or lactating
* Active, serious infections uncontrolled by antibiotics
* Any medical condition or reason that, in the investigator's opinion, makes the patient unsuitable to participate in this clinical trial
* History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride or the components of doxorubicin hydrochloride liposome or bortezomib, boron, or mannitol
* Any of the following conditions:

  * History of uncontrolled New York Heart Association class II-IV heart disease or clinical evidence of congestive heart failure
  * Myocardial infarction within the past 6 months
  * Uncontrolled angina
  * Severe uncontrolled ventricular arrhythmias, ECG evidence of acute ischemia, or active conduction system abnormalities
* Peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: Overall Response Rate (Complete and Partial)
timeFrame: Every 3 months
Secondary outcomes:
measure: Complete Response Rate
timeFrame: Every 3 months
measure: Time to Disease Progression
timeFrame: Every 3 monthsntil the date of first documented progression or date of death from any cause, whichever came first
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Kelvin Lee, MD
role: PRINCIPAL_INVESTIGATOR
References: