Doxorubicin Hydrochloride Liposome, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

Sponsor

Oncotherapeutics (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00742404

Collaborator

(none)

Enrollment

Locations

2.9

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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 tumor. Giving bortezomib together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving doxorubicin hydrochloride liposome together with bortezomib and dexamethasone works in treating patients with newly diagnosed multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: bortezomib Drug: dexamethasone Drug: pegylated liposomal doxorubicin hydrochloride Genetic: protein analysis Other: immunologic technique	Phase 2

Detailed Description

OBJECTIVES:

Primary

To determine the response rate (i.e., complete response, very good partial response , partial response, and minimal response) in patients with newly diagnosed multiple myeloma treated with pegylated liposomal doxorubicin hydrochloride, bortezomib, and dexamethasone.

Secondary

To assess the safety and tolerability of this regimen in these patients.
To determine the time to disease progression, time to response, duration of response, progression-free survival, and overall survival of patients treated with this regimen.

OUTLINE: Patients receive pegylated liposomal doxorubicin hydrochloride IV over 30-90 minutes, dexamethasone IV, and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Blood and urine samples are collected at baseline and periodically during study for M-protein analysis by electrophoresis and immunofixation.

After completion of study therapy, patients are followed periodically.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Pegylated Liposomal Doxorubicin, Bortezomib and Dexamethasone (DVD) for Patients With Newly Diagnosed Multiple Myeloma (MM)

Study Start Date :

Jul 1, 2008

Anticipated Primary Completion Date :

Jul 1, 2010

Outcome Measures

Primary Outcome Measures

Response rate (complete response, very good partial response, partial response, and minimal response) as assessed by modified Bladé criteria at baseline, on day 1 of each course, and at end-of-study []

Secondary Outcome Measures

Safety and tolerability as assessed by NCI CTCAE v3.0 []
Time to progression []
Time to response []
Duration of response []
Progression-free survival []
Overall survival []
Changes in serum M-protein []
Changes in 24-hour urine M-protein []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of multiple myeloma based on the following criteria:
Major criteria
Plasmacytomas on tissue biopsy (1)
Bone marrow plasmacytosis (> 30% plasma cells) (2)
Monoclonal immunoglobulin spike on serum electrophoresis IgG > 3.5 g/dL or IgA > 2.0 g/dL and kappa or lambda light chain excretion > 1 g/day on 24-hour urine protein electrophoresis (3)
Minor criteria
Bone marrow plasmacytosis (10% to 30% plasma cells) (a)
Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria (b)
Lytic bone lesions (c)
Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL (d)
Meets 1 of the following sets of diagnostic criteria:
Any two of the major criteria
Major criteria 1 and minor criteria b, c, and d
Major criteria 3 and minor criteria a or c
Minor criteria a, b, c, OR a, b, d
Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike ≥ 200 mg/24 hours, or evidence of lytic bone disease
No nonmeasurable disease (i.e., non-secretory or oligosecretory multiple myeloma)
Symptomatic, newly diagnosed, and previously untreated multiple myeloma
No POEMS syndrome (i.e., plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes)
No plasma cell leukemia

PATIENT CHARACTERISTICS:

Karnofsky performance status 60-100%
Life expectancy > 3 months
ANC ≥ 1,500/mm^{³ (≥ 1,000/mm}³ if bone marrow is extensively infiltrated)
Platelet count ≥ 75,000/mm^{³ (≥ 50,000/mm}³ if bone marrow is extensively infiltrated)
Hemoglobin ≥ 8.0 g/dL
AST and ALT ≤ 3.0 times upper limit of normal (ULN)
Serum bilirubin ≤ 2.0 times ULN
Creatinine clearance ≥ 30 mL/min OR creatinine > 10 mL/min and < 30 mL/min for patients with significant myelomatous involvement of the kidneys
Serum potassium ≥ lower limit of normal (LLN)
Serum sodium ≥ LLN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No prior malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
No peripheral neuropathy ≥ grade 2 within past 14 days
No impaired cardiac function or clinically significant cardiac disease, including any one of the following:
Myocardial infarction within the past 6 months
New York Heart Association class II-IV heart failure
Uncontrolled angina
Clinically significant pericardial disease
Severe uncontrolled ventricular arrhythmias
LVEF below normal by ECHO or MUGA scan
ECG evidence of acute ischemia or active conduction system abnormalities
Screening ECG abnormality must be documented by the investigator as not medically relevant
No severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL [3.5 mmol/L])
No poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could preclude study treatment
No known HIV positivity or hepatitis B or C positivity
Baseline testing for HIV and hepatitis B or C is not required
No history of allergic reaction attributable to compounds of similar chemical or biological composition to doxorubicin, bortezomib, boron, or mannitol

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior or concurrent anti-myeloma therapy except steroids
Prior prednisone for ≤ 4 days at a total of 400 mg (or an equivalent potency of another steroid) allowed
No concurrent corticosteroids (≥ 10 mg prednisone/day or equivalent) other than dexamethasone
More than 4 weeks since prior major surgery and recovered
Prior kyphoplasty with oncotherapeutic drugs allowed at the investigator's discretion
More than 4 weeks since prior immunotherapy, antibody therapy, or radiotherapy
More than 14 days since other prior and no other concurrent investigational drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Clinical Research Center, Incorporated	Tucson	Arizona	United States	85712
2	Comprehensive Blood and Cancer Center	Bakersfield	California	United States	93309-0633
3	San Diego Pacific Oncology and Hematology Associates, Incorporated - Escondido	Escondido	California	United States	92025
4	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California	United States	92354
5	Oncology Care Medical Associates - San Gabriel	Los Angeles	California	United States	90057
6	Desert Cancer Care	Rancho Mirage	California	United States	92270
7	Sutter Cancer Center at Roseville Medical Center	Roseville	California	United States	95661
8	Santa Barbara Hematology Oncology Medical Group at Cancer Center of Santa Barbara	Santa Barbara	California	United States	93105
9	James R. Berenson MD, Incorporated	West Hollywood	California	United States	90069
10	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
11	New York Medical College	Valhalla	New York	United States	10595
12	Charleston Hematology Oncology Associates, PA	Charleston	South Carolina	United States	29403