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Doxorubicin Hydrochloride Liposome, Melphalan, and Bortezomib in Treating Patients With Relapsed or Refractory Stage I, Stage II, or Stage III Multiple Myeloma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), August 2008
First Received: June 7, 2006   Last Updated: November 13, 2008   History of Changes
Sponsors and Collaborators: Herbert Irving Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00334932
  Purpose

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 Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: bortezomib
Drug: melphalan
Drug: pegylated liposomal doxorubicin hydrochloride
Phase I
Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Cancer Multiple Myeloma
Drug Information available for: Doxorubicin Doxorubicin hydrochloride Myocet Bortezomib Melphalan Sarcolysin Melphalan hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: Phase I/II Study of Liposomal Doxorubicin (Doxil®)/ Melphalan/Bortezomib (Velcade®) in Relapsed/Refractory Multiple Myeloma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of patients experiencing treatment-related ≥ grade 3 hematologic or nonhematologic toxicity or treatment-related death (phase I) [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to response (phase II) [ Designated as safety issue: No ]
  • Progression-free survival (phase II) [ Designated as safety issue: No ]
  • Overall survival (phase II) [ Designated as safety issue: No ]
  • Toxicities by NCI criteria (phase II) [ Designated as safety issue: Yes ]

Estimated Enrollment: 32
Study Start Date: February 2006
Estimated Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00334932

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi     877-827-3222        
United States, New York
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Clinical Trials Office - Herbert Irving Comprehensive Cancer C     212-305-8615        
Sponsors and Collaborators
Herbert Irving Comprehensive Cancer Center
Investigators
Principal Investigator: Ajai Chari, MD Herbert Irving Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Chari A, Kaplan L, Linker C, et al.: Phase I/II study of bortezomib in combination with liposomal doxorubicin and melphalan in relapsed or refractory multiple myeloma. [Abstract] Blood 106 (11): A-5182, 2005 .

Study ID Numbers: CDR0000471769, CPMC-AAAB6443
Study First Received: June 7, 2006
Last Updated: November 13, 2008
ClinicalTrials.gov Identifier: NCT00334932     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Study placed in the following topic categories:
Melphalan
Immunoproliferative Disorders
Immunologic Factors
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Bortezomib
Vascular Diseases
Paraproteinemias
Hemostatic Disorders
Immunosuppressive Agents
Doxorubicin
Protease Inhibitors
Multiple Myeloma
Anti-Bacterial Agents
Hemorrhagic Disorders
Antineoplastic Agents, Alkylating
Lymphoproliferative Disorders
Alkylating Agents
Neoplasms, Plasma Cell

Additional relevant MeSH terms:
Melphalan
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Blood Protein Disorders
Antineoplastic Agents
Physiological Effects of Drugs
Paraproteinemias
Hemostatic Disorders
Antibiotics, Antineoplastic
Hemorrhagic Disorders
Therapeutic Uses
Cardiovascular Diseases
Alkylating Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Hematologic Diseases
Bortezomib
Vascular Diseases
Enzyme Inhibitors
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Protease Inhibitors
Multiple Myeloma
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Lymphoproliferative Disorders
Neoplasms, Plasma Cell

ClinicalTrials.gov processed this record on May 06, 2009