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TerminatedNCT00849251Updated Sep 8, 2017Results posted

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

A Phase 1/2 interventional study of cyclophosphamide and pegylated liposomal doxorubicin hydrochloride in Refractory Multiple Myeloma, Stage I Multiple Myeloma and Stage II Multiple Myeloma, sponsored by University of Washington. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-09-08.

Sponsored by University of Washington · Phase 1/2, Interventional, and Treatment

Why this study was terminated
One of the study drugs is not available.
Phase
Phase 1/2
Study type
Interventional
Enrollment
31
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

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

Read the 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.

02

Conditions studied

  • Refractory Multiple Myeloma
  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma

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03

In context

Multiple Myeloma

3,712 studies on the registry are indexed under Multiple Myeloma; 752 are open to participants now.

This study's enrollment of 31 is below the median of 41 across 2,965 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

University of Washington is the lead sponsor of 1,431 studies on the registry; 226 are open to participants now.

Of its 158 completed or terminated interventional studies of FDA-regulated products, 136 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
31 participants (actual)

Study arms

  • 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 · Drug: pegylated liposomal doxorubicin hydrochloride · Drug: bortezomib · Drug: dexamethasone

Interventions

06

What researchers measure

Primary outcomes

  1. 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]

    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.

    Time frame: Up to 90 days after initiation of study treatment

  2. Disease Response Rate (Cohort II)

    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.

    Time frame: up to 28 days after last cycle of treatment

  3. 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]

    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.

    Time frame: Up to 90 days after initiation of study treatment

07

Results

Posted Sep 8, 2017

Participant flow

Participant flow — Overall Study
MilestoneRelapsed Disease (Cohort I)Newly Diagnosed Disease (Cohort II)
Started625
Completed524
Not completed11

Outcome measures

PrimaryMaximum 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]

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.

Time frame:
Up to 90 days after initiation of study treatment
Reported as:
Number · mg/m2
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]
mg/m2Relapsed Disease
MTD cyclophosphamide300
MTD bortezomib1.6
MTD liposomal doxorubicin30
PrimaryDisease Response Rate (Cohort II)

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.

Time frame:
up to 28 days after last cycle of treatment
Reported as:
Count of participants · Participants
Disease Response Rate (Cohort II)
ParticipantsNewly Diagnosed Patients
Complete response (CR)2
Near complete response (nCR)2
Very good partial response (VGPR)3
Partial response (PR)11
Stable disease (SD)6
PrimaryMaximum 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]

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.

Time frame:
Up to 90 days after initiation of study treatment
Reported as:
Number · mg
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]
mgRelapsed Disease (Cohort I)
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]40

Adverse events

Collected over Through 45 days after the last dose of study drug.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Chemotherapy and Enzyme Inhibitor)—1/31 (3.2%)31/31 (100%)
Most frequent serious events
Most frequent serious events
EventTreatment (Chemotherapy and Enzyme Inhibitor)
Thromboembolic eventVascular disorders1/31
Most frequent other events
Showing 10 of 52
Most frequent other events
EventTreatment (Chemotherapy and Enzyme Inhibitor)
FatigueGeneral disorders18/31
NauseaGastrointestinal disorders10/31
ConstipationGastrointestinal disorders10/31
AnemiaBlood and lymphatic system disorders8/31
Peripheral neuropathyNervous system disorders7/31
HypoalbuminemiaInvestigations5/31
NeutropeniaInvestigations5/31
Hand foot and mouth diseaseInfections and infestations4/31
LeukopeniaInvestigations4/31
InsomniaPsychiatric disorders3/31

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Treatment (Chemotherapy and Enzyme Inhibitor)
<=18 years0
Between 18 and 65 years25
>=65 years6
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Chemotherapy and Enzyme Inhibitor)
Female17
Male14
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Treatment (Chemotherapy and Enzyme Inhibitor)
Hispanic or Latino2
Not Hispanic or Latino24
Unknown or Not Reported5
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (Chemotherapy and Enzyme Inhibitor)
American Indian or Alaska Native0
Asian1
Native Hawaiian or Other Pacific Islander0
Black or African American1
White29
More than one race0
Unknown or Not Reported0
08

Study locations

1 site
  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    Seattle, Washington 98109, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 8, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00849251
Responsible party
Pamela S Becker (Principal Investigator, University of Washington) — Principal investigator
First posted
Feb 23, 2009
Start date
Nov 2008
Primary completion
Dec 2011
Completion
Jun 2015
Results posted
Sep 8, 2017
Last update
Sep 8, 2017

Study contacts

Pamela Becker
principal investigator · Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in Aug 2017. You cannot join it, but the record below documents what was studied.

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Studies of the drugs tested here: Cyclophosphamide · Liposomal doxorubicin · Bortezomib · Dexamethasone

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