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Bortezomib, Doxorubicin Hydrochloride Liposome, and Dexamethasone Followed by Thalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Multiple Myeloma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00458705
First received: April 9, 2007
Last updated: March 8, 2013
Last verified: March 2013
  Purpose

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 and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Thalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving bortezomib together with doxorubicin hydrochloride liposome and dexamethasone followed by thalidomide, dexamethasone, and bortezomib may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects and how well giving bortezomib together with doxorubicin hydrochloride liposome and dexamethasone followed by thalidomide and dexamethasone with or without bortezomib works in treating patients with multiple myeloma.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: bortezomib
Drug: dexamethasone
Drug: pegylated liposomal doxorubicin hydrochloride
Drug: thalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Bortezomib + Pegylated Liposomal Doxorubicin (Doxil) + Dexamethasone Followed by Thalidomide + Dexamethasone or Bortezomib + Thalidomide + Dexamethasone for Patients With Symptomatic Untreated High-Risk or Primary Resistant Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Disease response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 45
Study Start Date: November 2006
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination therapy
Combination therapy with bortezomib, pegylated liposomal doxorubicin and dexamethasone (BDD) followed by either thalidomide and dexamethasone (TD) or bortezomib, thalidomide and dexamethasone in patients with symptomatic untreated high-risk or primary resistant multiple myeloma. Three cycles of BDD will be administered. Patients who respond after three cycles will receive two cycles of TD. Patients with stable or progressive disease after three cycles of BDD receive two cycles of bortezomib, thalidomide and dexamethasone. If at any point during the study a patient achieves a complete response (CR), the patient will be given the option to discontinue treatment on-study.
Drug: bortezomib Drug: dexamethasone Drug: pegylated liposomal doxorubicin hydrochloride Drug: thalidomide

Detailed Description:

OBJECTIVES:

  • Determine the efficacy and safety of bortezomib, pegylated doxorubicin hydrochloride liposome, and dexamethasone followed by thalidomide and dexamethasone with or without bortezomib in patients with symptomatic high-risk or primary resistant multiple myeloma.

OUTLINE: Patients receive BDD comprising bortezomib IV on days 1, 4, 8, and 11; pegylated doxorubicin hydrochloride liposome IV over 60-90 minutes on day 4; and oral dexamethasone on day 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Patients achieving response to BDD receive oral thalidomide on days 1-28 and oral dexamethasone on days 1-4, 9-12, and 17-20. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Patients experiencing stable or progressive disease on BDD receive oral thalidomide on days 1-28; oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, 12, and 17-21; and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically and serologically confirmed multiple myeloma meeting one of the following criteria:

    • High-risk myeloma, defined as symptomatic International Staging System (ISS) stage 2 or 3 multiple myeloma
    • Soft-tissue involvement with myeloma in the form of a soft-tissue plasmacytoma
    • Extension of a plasmacytoma into soft tissues
    • Primary resistant myeloma, defined as unchanged or progressive myeloma despite two courses of standard treatment
  • No ISS stage 1 multiple myeloma without soft-tissue involvement
  • No smoldering myeloma

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-3
  • Life expectancy > 16 weeks
  • Absolute granulocyte count ≥ 1,500/mm³ (unless low granulocyte counts are due to multiple myeloma)
  • Platelet count ≥ 100,000/mm³ (unless low platelet counts are due to multiple myeloma)
  • Bilirubin ≤ 2.0 mg/dL
  • AST and ALT < 3 times upper limit of normal (ULN)
  • Alkaline phosphatase < 3 times ULN
  • LVEF ≥ 50% by MUGA or ECHO
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception 4 months prior to, during, and for 4 weeks after completion of study treatment
  • No active thromboembolic disease on anticoagulation
  • No active angina or myocardial infarction within the past 6 months
  • No pre-existing neuropathy or sensory or neuropathic pain ≥ grade 2
  • No concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix

    • Prior malignancies that have not required antitumor treatment within the past 24 months allowed
    • Patients with a history of stage I or II (T1a/b) prostate cancer (detected incidentally at transurethral resection of prostate [TURP] and comprising < 5% of resected tissue) allowed if the prostate-specific antigen has remained normal since TURP
  • No known HIV positivity or AIDS-related illness
  • No other medical condition or reason that, in the opinion of the investigator, would preclude study compliance
  • No history of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride or to components of pegylated doxorubicin hydrochloride liposome, bortezomib, boron, or mannitol

PRIOR CONCURRENT THERAPY:

  • Prior radiotherapy allowed
  • No more than 2 courses of prior initial chemotherapy for multiple myeloma
  • No prior bortezomib
  • No prior high-dose steroids (not including taper) for more than 1 month in duration for emergent indications, such as hypercalcemia or life-threatening lesions (e.g., spinal cord compromise) (in high-risk patients)
  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: NCT00458705

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Heather Landau, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00458705     History of Changes
Other Study ID Numbers: 06-067, P30CA008748, MSKCC-06067
Study First Received: April 9, 2007
Last Updated: March 8, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Doxorubicin
Liposomal doxorubicin
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics

ClinicalTrials.gov processed this record on November 23, 2014