Doxorubicin Hydrochloride Liposome, Melphalan, and Bortezomib in Treating Patients With Relapsed or Refractory Stage I, Stage II, or Stage III Multiple Myeloma

Sponsor

Herbert Irving Comprehensive Cancer Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT00334932

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome and melphalan, 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. Giving doxorubicin hydrochloride liposome and melphalan together with bortezomib may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of doxorubicin hydrochloride liposome , melphalan, and bortezomib and to see how well they work in treating patients with relapsed or refractory stage I, stage II, or stage III multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: bortezomib Drug: melphalan Drug: pegylated liposomal doxorubicin hydrochloride	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the safety and tolerability of doxorubicin HCl liposome, melphalan, and bortezomib in patients with relapsed or refractory stage I-III multiple myeloma.
Determine the maximum tolerated dose (MTD) of this regimen in these patients.

Secondary

Determine the overall response rate, including complete, near-complete, partial, and minimal response rate, in patients treated with this regimen.
Determine the time to response, progression-free survival, and overall survival of patients treated with this regimen.
Determine the toxic effects of this regimen at the MTD in these patients.

OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II study.

Phase I: Patients receive doxorubicin HCl liposome IV over 30-60 minutes and melphalan IV over 30 minutes on day 1 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome, melphalan, and bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 4 of 6 patients experience dose-limiting toxicity after 2 courses of therapy.

Phase II: Patients receive doxorubicin HCl liposome, melphalan, and bortezomib at the MTD as in phase I.

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

PROJECTED ACCRUAL: Approximately 32 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Primary Purpose:

Treatment

Official Title:

Phase I/II Study of Liposomal Doxorubicin (Doxil®)/ Melphalan/Bortezomib (Velcade®) in Relapsed/Refractory Multiple Myeloma

Study Start Date :

Feb 1, 2006

Anticipated Primary Completion Date :

Jan 1, 2010

Outcome Measures

Primary Outcome Measures

Proportion of patients experiencing treatment-related ≥ grade 3 hematologic or nonhematologic toxicity or treatment-related death (phase I) []

Secondary Outcome Measures

Time to response (phase II) []
Progression-free survival (phase II) []
Overall survival (phase II) []
Toxicities by NCI criteria (phase II) []

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
Stage I, II, or III disease according to Durie-Salmon staging criteria
Progressive disease, defined as one of the following:
For secretory disease:
A 25% increase in serum M-protein or Bence Jones protein (an absolute increase of 0.5 g/dL serum M-protein or ≥ 200 mg/24 hours of urine light chain excretion)
For nonsecretory disease:
Bone marrow biopsy with > 25% increase in plasma cells or an absolute increase of ≥ 10% over prior known level
Development of new or worsening existing lytic bone lesions or soft tissue plasmacytomas
Hypercalcemia (i.e., calcium > 11.5 mg/dL)
Relapsed after complete response
Must have received ≥ 2 of the following therapeutic regimens for multiple myeloma:
Nonmyeloablative transplantation
No significant graft-versus-host disease
At least 30 days since prior immunosuppressive therapy (concurrent prednisone allowed provided dose is ≤ 10 mg daily)
Mobilization with chemotherapy followed by either single or tandem autologous stem cell transplantation (considered 1 prior regimen)
Mobilization with chemotherapy followed by autologous and subsequent nonmyeloablative allogeneic stem cell transplantation (considered 1 prior regimen)
Any combination of drugs given concurrently (considered 1 prior regimen)

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 3 months
Absolute neutrophil count > 1,000/mm^3 (no colony-stimulating factors)
Platelet count > 50,000/mm^3 (no transfusion support)
Bilirubin ≤ 2.0 mg/dL
AST ≤ 4 times upper limit of normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment
No history of allergic reaction to compounds containing boron or mannitol
No active uncontrolled viral (including HIV), bacterial, or fungal infection
No motor or sensory neuropathy ≥ grade 2
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 arrhythmia
No acute ischemia by EKG
LVEF ≥ 35% by MUGA (MUGA required in patients whose lifetime cumulative doxorubicin hydrochloride dose > 400 mg/m^2)

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No grade III or IV toxicity due to previous antineoplastic therapy (except alopecia)
At least 3 weeks since prior chemotherapy
No prior doxorubicin HCl liposome, melphalan, and bortezomib as combination therapy (single or two-drug combinations of these are allowed)
No concurrent corticosteroids (≤ 10 mg prednisone/day or equivalent allowed)
No other concurrent chemotherapy
No concurrent thalidomide
No other concurrent investigational therapy
No other concurrent antineoplastic treatment for multiple myeloma, including clarithromycin
No concurrent radiation therapy
No concurrent nonsteroidal anti-inflammatory agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
2	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York	United States	10032