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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

Primary Purpose

Multiple Myeloma and Plasma Cell Neoplasm

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bortezomib
dexamethasone
pegylated liposomal doxorubicin hydrochloride
thalidomide
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma and Plasma Cell Neoplasm focused on measuring stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Combination therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

Disease Response
The response of myeloma to BDDTD will be assessed by standard electrophoretic and immunofixation tests of blood and urine for a monoclonal protein (M protein), and bone marrow aspirate and biopsy. These tests will be performed at enrollment and at the conclusion of therapy.

Secondary Outcome Measures

Full Information

First Posted
April 9, 2007
Last Updated
December 16, 2015
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00458705
Brief Title
Bortezomib, Doxorubicin Hydrochloride Liposome, and Dexamethasone Followed by Thalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Multiple Myeloma
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
November 2006 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma and Plasma Cell Neoplasm
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Combination therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
bortezomib
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Type
Drug
Intervention Name(s)
pegylated liposomal doxorubicin hydrochloride
Intervention Type
Drug
Intervention Name(s)
thalidomide
Primary Outcome Measure Information:
Title
Disease Response
Description
The response of myeloma to BDDTD will be assessed by standard electrophoretic and immunofixation tests of blood and urine for a monoclonal protein (M protein), and bone marrow aspirate and biopsy. These tests will be performed at enrollment and at the conclusion of therapy.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heather Landau, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21824051
Citation
Landau H, Pandit-Taskar N, Hassoun H, Cohen A, Lesokhin A, Lendvai N, Drullinsky P, Schulman P, Jhanwar S, Hoover E, Bello C, Riedel E, Nimer SD, Comenzo RL. Bortezomib, liposomal doxorubicin and dexamethasone followed by thalidomide and dexamethasone is an effective treatment for patients with newly diagnosed multiple myeloma with Internatinal Staging System stage II or III, or extramedullary disease. Leuk Lymphoma. 2012 Feb;53(2):275-81. doi: 10.3109/10428194.2011.606943. Epub 2011 Sep 23.
Results Reference
result

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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

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