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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2008 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00334932
First received: June 7, 2006
Last updated: January 9, 2014
Last verified: August 2008
  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 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I/II Study of Liposomal Doxorubicin (Doxil®)/ Melphalan/Bortezomib (Velcade®) in Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 .

ClinicalTrials.gov Identifier: NCT00334932     History of Changes
Other Study ID Numbers: CDR0000471769, CPMC-AAAB6443
Study First Received: June 7, 2006
Last Updated: January 9, 2014
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

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

ClinicalTrials.gov processed this record on September 16, 2014