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Pegylated Liposomal Doxorubicin Hydrochloride, Bortezomib, Cyclophosphamide, and Dexamethasone in Treating Patients With Multiple Myeloma

This study has been terminated.
(One of the study drugs is not available.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00849251
First Posted: February 23, 2009
Last Update Posted: September 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Pamela S Becker, University of Washington
  Purpose

RATIONALE: Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride and cyclophosphamide, 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 and by blocking blood flow to the cancer. Giving pegylated liposomal doxorubicin hydrochloride together with bortezomib, cyclophosphamide, and dexamethasone may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects of giving pegylated liposomal doxorubicin hydrochloride together with bortezomib, cyclophosphamide, and dexamethasone and to see how well it works in treating patients with multiple myeloma


Condition Intervention Phase
Refractory Multiple Myeloma Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma Drug: cyclophosphamide Drug: pegylated liposomal doxorubicin hydrochloride Drug: bortezomib Drug: dexamethasone Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Combination Pegylated Liposomal Doxorubicin, Bortezomib, Cyclophosphamide, and Dexamethasone for Multiple Myeloma (PLD-BCD)

Resource links provided by NLM:


Further study details as provided by Pamela S Becker, University of Washington:

Primary Outcome Measures:
  • Maximum Tolerated Dose of This Combination of Drugs as Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Cohort 1) [MTD Cyclophosphamide, MTD Bortezmib, MTD Docxorubicin] [ Time Frame: Up to 90 days after initiation of study treatment ]
    If 3 patients of cohort 1 require dose reduction of one or more of the medications for toxicity attributed to the drug or drugs, then the starting dose level will be reduced for that drug or drugs for future patients. The initial dosing of drugs for cohort 2 will be permitted to be one dose level above the maximal tolerated doses of cohort 1. Note that this Outcome Measure shows MTD for cyclophosphamide, bortezomib and doxorubicin. MTD for dexamethasone is include in a separate table due to the different Unit of Measure.

  • Disease Response Rate (Cohort II) [ Time Frame: up to 28 days after last cycle of treatment ]
    Disease response using Blade Multiple Myeloma Response Criteria in newly diagnosed (Cohort II) patients who completed at least one cycle of treatment. There were 24 evaluable patients in Cohort II.

  • Maximum Tolerated Dose of This Combination of Drugs as Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Cohort 1). [Dexamethasone MTD] [ Time Frame: Up to 90 days after initiation of study treatment ]
    If 3 patients of cohort 1 require dose reduction of one or more of the medications for toxicity attributed to the drug or drugs, then the starting dose level will be reduced for that drug or drugs for future patients. The initial dosing of drugs for cohort 2 will be permitted to be one dose level above the maximal tolerated doses of cohort 1. Note that this Outcome Measure will only describe the MTD for dexamethasone. Dexamethasone could not be reported with the MTD for the other three drugs due to a different Unit of Measure.


Enrollment: 31
Study Start Date: November 2008
Study Completion Date: June 2015
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy and enzyme inhibitor)
Patients receive cyclophosphamide IV or PO over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Drug: cyclophosphamide
Given IV or PO
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Other Names:
  • CAELYX
  • Dox-SL
  • DOXIL
  • doxorubicin hydrochloride liposome
  • LipoDox
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine efficacy of this novel combination in newly diagnosed patients with multiple myeloma.

SECONDARY OBJECTIVES:

I. To determine the toxicity of this novel combination regimen in previously treated patients and newly diagnosed patients with multiple myeloma.

OUTLINE:

Patients receive cyclophosphamide intravenously (IV) or orally (PO) over 1 hour, bortezomib IV over 3 minutes, and dexamethasone IV or PO on days 1, 8, and 15. Patients also receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of treatment, patients are followed up every 3 months for 2 years, then annually up to 5 years.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cohort 1: Relapsed, refractory patients with multiple myeloma who have failed at least one prior regimen not including dexamethasone alone
  • Cohort 2: Newly diagnosed patients with previously untreated multiple myeloma; prior dexamethasone permitted; not to exceed 320 mg
  • Diagnosis of multiple myeloma with quantifiable monoclonal protein or light chain identified by serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), or serum free light chain assay
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count >= 1.5
  • Platelet count >= 75,000 unless slightly lower due to disease with the approval of the principal investigator (PI)
  • Serum creatinine =< 2.0 mg/dL
  • Serum bilirubin =< 1.2
  • Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Alkaline phosphatase =< 2.5 x ULN
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Left ventricular ejection fraction greater than or equal to 50% by multi gated acquisition scan (MUGA)
  • Female subjects must be post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study; female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment
  • Male patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment

Exclusion Criteria:

  • Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol
  • Use of other anticancer therapy within 15 days or before study entry; the patient must have recovered from all acute non-hematological toxicities from any previous therapy
  • Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment, despite appropriate antibiotics or other treatment; for cardiac dysfunction, myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection) on antiviral, antibiotic and antifungal treatment
  • Patient has >= Grade 2 peripheral neuropathy within 14 days before enrollment
  • Patient has hypersensitivity to bortezomib, boron or mannitol
  • Pregnant or lactating patients
  • Cumulative dose of doxorubicin of 400 mg/m^2 or greater, or if this level would be exceeded during the current study
  • Any significant concurrent illness, condition, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
  • Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy including the following:
  • Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed;
  • Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed;
  • Prior autologous stem cell transplant (Cohort 2 only);
  • Prior allogeneic stem cell transplant;
  • Patient has received other investigational drugs within 14 days before enrollment
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00849251


Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
Principal Investigator: Pamela Becker Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

Responsible Party: Pamela S Becker, Principal Investigator, University of Washington
ClinicalTrials.gov Identifier: NCT00849251     History of Changes
Other Study ID Numbers: 6817
NCI-2009-01665 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: February 20, 2009
First Posted: February 23, 2009
Results First Submitted: March 4, 2017
Results First Posted: September 8, 2017
Last Update Posted: September 8, 2017
Last Verified: August 2017

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
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
Dexamethasone acetate
Dexamethasone
Liposomal doxorubicin
Cyclophosphamide
Doxorubicin
Bortezomib
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists