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Multiple MyelomaPhase 1/2NCT00750815

Cyclophosphamide, VELCADE, DOXIL, and Dexamethasone, (CVDD) in Newly Diagnosed Patients With Multiple Myeloma (MM)

A Phase 1/2 study testing Cyclophosphamide and Bortezomib; Pegylated Liposomal Doxorubicin; Dexamethasone (VDD) in people with Multiple Myeloma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Cyclophosphamide is a chemotherapy agent with known activity in myeloma. The new regimen that we will test in this study is called CVDD and contains Cyclophosphamide with Bortezomib (VELCADE), Pegylated Liposomal Doxorubicin (DOXIL®, PLD), and Dexamethasone (VDD). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Cyclophosphamide and Bortezomib; Pegylated Liposomal Doxorubicin; Dexamethasone (VDD)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
1 siteUnited States
Study dates
Sep 2008to May 2013
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Understand and voluntarily sign informed consent form; equal to or greater than 18 years of age at time of consent
  • Able to adhere to the study visit schedule and other protocol requirements
  • Diagnosed active multiple myeloma
  • Measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL) or urine (≥ 0.2 g excreted in a 24-hour urine collection sample), or serum involved free light chains ( >10mg/dl) provided that the k/l ratio is abnormal
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Performance status of 3 allowed if related to bony disease.
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  • Bilirubin ≤ 1.5x upper limits of normal (ULN)
  • Liver enzymes: alanine transaminase (ALT)or aspartic transaminase (AST) ≤ 2.5 x ULN. In the presence of liver metastases, AST / ALT, alkaline phosphatase and total bilirubin must not exceed 3x upper limit of normal (i.e.: must be ≤ 3x ULN).
  • Adequate bone marrow function:
  • Absolute neutrophil count (ANC) ≥ 1,000 cells/mm³ (1.0 x 10^9/L). Patients with bone marrow >50% plasma cells are permitted to have a neutrophil count of < 1,000 cells/mm³.
  • Platelets ≥ 100,000 cells/mm³. Patients with bone marrow >50% plasma cells are permitted to have a Platelet count ≤ 100, 000 cells/mm³
  • Hemoglobin > 8 g/dL (transfusion allowed to increase the Hgb)
  • Adequate renal function: Creatinine ≤ 2.5 mg/dL
  • Must have 2-d echocardiogram or multigated acquisition (MUGA) scan indicating left ventricular ejection fraction (LVEF) ≥ 50% within 42 days prior to first dose of study drug. A MUGA scan or 2- d Echocardiogram may be used, but the same test must be used throughout study) to evaluate LVEF.
  • Women of childbearing potential(WCBP)† must have negative serum or urine pregnancy test 10 to 14 days prior to starting therapy. Patients with reproductive potential must use an adequate contraceptive method during treatment and for 3 months after completing treatment. In addition, sexually active WCBP must agree to use adequate contraceptive methods per the requirements outlined in protocol document.
  • Patients treated with local radiotherapy with or without concomitant exposure to steroids, for pain control or management of cord/nerve root compression, are eligible. 4 weeks must have lapsed since last date of radiotherapy. Patients who require concurrent radiotherapy should have entry to the protocol deferred until radiotherapy is completed and 4 weeks have passed since last date of therapy.

Who cannot join

  • Ongoing severe infection requiring intravenous antibiotic treatment
  • Life expectancy < 3 months
  • Prior malignancy, except; adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the participant has been disease-free for at least 5 years. Concurrent prostate cancer for which patient is receiving therapy will not be considered an exclusion if prostatic specific antigen (PSA) has been stable for 3 years.
  • Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
  • Patients receiving therapeutic dosages of steroids for multiple myeloma
  • Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
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  • Uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias, pulmonary, hepatic and renal diseases unless renal insufficiency is felt to be secondary to multiple myeloma
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form
  • Pregnant or breast-feeding females. Lactating females must agree not to breast-feed.
  • Any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Prior chemotherapy for multiple myeloma, except for radiation to symptomatic bony disease, plasmapheresis for hyperviscosity, kyphoplasty and/or vertebroplasty
  • History of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride (HC1) or the components of DOXIL®
  • Prior anthracycline dose exceeding 360 mg/m² for doxorubicin (including DOXIL) or 720 mg/m² for epirubicin
  • Grade 2 or higher peripheral neuropathy on clinical examination within 14 days before enrollment
  • Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome or plasma cell leukemia
  • Hypersensitivity to bortezomib, boron or mannitol
  • Has received other investigational drugs within 14 days before enrollment

Trial locations and contacts

1 site in 1 country.

United States1 site
  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: An Open Label Phase I/II Study of the Safety and Efficacy of Cyclophosphamide, Bortezomib (VELCADE), Pegylated Liposomal Doxorubicin (DOXIL), and Dexamethasone, (CVDD) in Newly Diagnosed Patients With Multiple Myeloma

Cyclophosphamide is a chemotherapy agent with known activity in myeloma. The new regimen that we will test in this study is called CVDD and contains Cyclophosphamide with Bortezomib (VELCADE), Pegylated Liposomal Doxorubicin (DOXIL®, PLD), and Dexamethasone (VDD).

The purpose of this study is to determine if the addition of another type of chemotherapy agent, Cyclophosphamide, to the regimen VDD (CVDD) is well tolerated and improves response rates in myeloma. We will also find the highest safe dose of the study drugs taken together that a patient can tolerate, and how long it takes for multiple myeloma patients to respond after they have taken the study drugs and how long the response lasts.

Read the detailed description

The first cohort of 3 participants enrolled into Phase I of the study will receive dose level 1. A full safety evaluation will be conducted when these participants have completed one cycle (21 days) of combination therapy. Further patient accrual will be suspended while the safety data is evaluated at each dose level.

Dose escalation for subsequent patients will proceed through dose levels 2, 3 and 4 as follows:

  • If no dose limiting toxicity (DLT) is reported in the first 3 participants at a dose level, that dose level will be considered safe and 3 participants will be enrolled at the next dose level. If 1/3 participants in a cohort at a dose level has a DLT, the dose level will be expanded to obtain 6 evaluable participants.
  • If > 1 of 3 participants in a cohort experience DLT, that dose level will not be considered safe. No further dose escalation will take place, and the immediate lower dose level will be considered the maximum planned dose (MPD) if 6 patients had been enrolled at that dose level. Otherwise, expand the immediate lower dose level to 6 evaluable patients*.
  • If there are < 2 participants with a DLT among the expanded cohort of 6 evaluable participants, a cohort of 3 participants will be enrolled in the next higher dose level.
  • If there are 2 or more participants with a DLT among the expanded cohort of 6 evaluable participants, that dose level will not be considered safe. No further dose escalation will take place, and the immediate lower dose level will be considered the MPD if 6 patients had been enrolled at that dose level. Otherwise, expand the immediate lower dose level to 6 evaluable patients*.
  • * If DLT occurs in no more than 1 patient in the expanded dose cohort, then that dose level will be considered MPD. Otherwise, the dose will be further de-escalated in a similar fashion until the MPD is reached.
Being tested
Cyclophosphamide, Bortezomib; Pegylated Liposomal Doxorubicin; Dexamethasone (VDD)
Keywords
B Cell, hematologic malignancy, plasma, bone marrow
Medical subject headings
Multiple Myeloma, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called Cytoxan

    Enroll patients into 4 different dose levels. The dose of Cyclophosphamide they receive will depend on how many patients have been treated.

  • Bortezomib; Pegylated Liposomal Doxorubicin; Dexamethasone (VDD)Drug

    Also called VELCADE, DOXIL®, PLD, CVDD

    Patients will receive Bortezomib, Pegylated Liposomal Doxorubicin and Dexamethasone at standard doses.

Study groups in NCT00750815
Study groupRoleWhat they receive
A. Phase I - Dose EscalationExperimentalDose of Cyclophosphamide to depend on how many patients we treated: * Dose Level 1: Cyclophosphamide 250 mg /m^2 IV Day 1; VELCADE, 1.0 mg/m^2 IV days 1,4,8, and 11; DOXIL 30 mg/m^2 Day 4; Dexamethasone 20 mg orally daily on days 1-2,4-5,8-9,11-12 * Dose Level 2: Cyclophosphamide 500 mg /m^2 IV Day 1; VELCADE, 1.0 mg/m^2 IV days 1,4,8, and 11; DOXIL 30 mg/m^2 Day 4; Dexamethasone 20 mg orally daily on days 1-2,4-5,8-9,11-12 * Dose Level 3: Cyclophosphamide 750 mg /m^2 IV Day 1; VELCADE, 1.0 mg/m^2 IV days 1,4,8, and 11; DOXIL 30 mg/m^2 Day 4; Dexamethasone 20 mg orally daily on days 1-2,4-5,8-9,11-12 * Dose Level 4: Cyclophosphamide 750 mg /m^2 IV Day 1; VELCADE, 1.3 mg/m^2 IV days 1,4,8, and 11; DOXIL 30 mg/m^2 Day 4; Dexamethasone 20 mg orally daily on days 1-2,4-5,8-9,11-12
Receives: Drug: Cyclophosphamide; Drug: Bortezomib; Pegylated Liposomal Doxorubicin; Dexamethasone (VDD)
B. Phase II - Maximum Planned Dose (MPD)ExperimentalParticipants received Cyclophosphamide and VELCADE at Level 4 (the MPD) at the same schedule of the Phase I study. Pegylated doxorubicin and Dexamethasone were given at the same doses and schedule as the Phase I part of study.
Receives: Drug: Cyclophosphamide; Drug: Bortezomib; Pegylated Liposomal Doxorubicin; Dexamethasone (VDD)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I - Maximum Planned Dose (MPD) Level

    Maximum Phase II planned dose of cyclophosphamide when given in combination with bortezomib, pegylated liposomal doxorubicin and Dexamethasone (CVDD) in participants with newly diagnosed active multiple myeloma. Dose levels 1, 2, 3, 4 as outlined in Treatment Arm A.

    If no dose limiting toxicity (DLT) was reported in the first 3 participants at a dose level, that dose level was to be considered safe and 3 participants would be enrolled at the next dose level. If 1/3 participants in a cohort at a dose level had dose limiting toxicity (DLT), the dose level would be expanded to obtain 6 evaluable participants. MPD reflects the highest dose of drug that did not cause a DLT in 33% of participants.

    Measured: 9 months

  2. Phase II: Overall Response Rate (ORR)

    Best response to CVDD chemotherapy. Overall Response: Partial Response (PR) + Very Good Partial Response (VGPR) + Complete Response (CR). PR: ≥ 50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein with urine M-protein level < 100 mg per 24 hours; CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow.

    Measured: Up to 6 months

Secondary outcomes (2)
  1. Phase II: Progression-Free Survival (PFS)

    Progression-free survival after CVDD in participants with newly diagnosed active multiple myeloma. PFS: time from the initiation of therapy to progression, relapse or death from any causes.

    Progressive Disease (PD): Progressive Disease requires any one or more of the following:

    Increase of ≥ 25% from baseline in:

    • serum M-component and /or (the absolute increase must be ≥ 0.5 g/dL)
    • urine M-component and/or (the absolute increase must be ≥ 200 mg/24 h)

    Measured: Up to 50.9 months

  2. Phase II: Two Year Overall Survival (OS)

    Overall survival by disease risk stratification after CVDD. OS: time from initiation of therapy until death from any cause.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Sep 2008 (estimated)
  2. Study startSep 2008
  3. Primary completionDec 2012
  4. Study completionMay 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00750815
Sponsor's protocol ID
MCC-15399
Other IDs
106692, Millennium X05248, DOXILMMY2008
Status last verified
Sep 2013
First submitted
10 Sep 2008
Last updated
20 Jan 2014
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cyclophosphamide and Bortezomib; Pegylated Liposomal Doxorubicin; Dexamethasone (VDD) in people with Multiple Myeloma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I - Maximum Planned Dose (MPD) Level (time frame: 9 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2014.

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