Multiple MyelomaPhase 2NCT00148317

Phase II Study of Velcade, Decadron, and Doxil Followed by Cyclophosphamide in Multiple Myeloma

A Phase 2 study testing Bortezomib, dexamethasone and liposomal doxorubicin in people with Multiple Myeloma, run by Weill Medical College of Cornell University 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

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Trial summary

PRIMARY STUDY OBJECTIVES To evaluate the efficacy of the combination of bortezomib, dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide as a therapy for two different subsets of multiple myeloma patients: 1. Patients post first line therapy 2. 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?: Bortezomib, dexamethasone and liposomal doxorubicin
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 38 participants
Where: 1 siteUnited States
Study dates: Jun 2005to Nov 2012
Phase: Phase 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

Subject must voluntarily sign and understand written informed consent.
Confirmed diagnosis of multiple myeloma as specified by the SWOG criteria and is detailed in Appendix I.
Measurable disease as defined the following:
For patients post induction therapy, any measurable paraprotein in the serum or urine and/or any plasmacytoma present on physical exam or imaging.
For patients with relapsed/refractory disease, > 0.5 g/dL serum monoclonal protein, > 0.1 g/dL serum free light chains, > 0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s).
Age > or = than 18 years at the time of signing the informed consent form.

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Karnofsky performance status> or =70% (>60% if due to bony involvement of myeloma).
Group A (post-induction therapy)- patients who have received only one prior treatment regimen (eg VAD, Thal/Dex, BLT-D, MP, BiRD, or DVd) with at least 20 patients having received a Revlimid based regimen or Group B(>1st line of therapy)- patients with relapsed/refractory multiple myeloma who have received two or more prior treatment regimens .
If the patient is a woman of childbearing age, she must have a negative serum or urine pregnancy test within 7 days of starting study and must use effective contraception throughout the course of the study.
Life expectancy > 12 weeks.
Absolute neutrophil count (ANC)> or = 1500 cells/mm3 (> or = 1000 for patients with bone marrow biopsy displaying > 50% involvement by myeloma)
Platelets count > or = 50,000/mm3 (> or = 30,000 for patients with bone marrow biopsy displaying > 50% involvement by myeloma)
Hemoglobin > 9.0 g/dL
Serum SGOT/AST <3.0 x upper limits of normal (ULN)
Serum SGPT/ALT <3.0 x upper limits of normal (ULN)
Serum creatinine < 2.5 mg/dL or creatinine clearance > 40ml/min
Serum total bilirubin < 1.5 x ULN
Patients must have a MUGA scan with LVEF >50%

Who cannot join

Patients with non-secretory MM (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine) unless measurable disease is available with imaging techniques such as MRI and PET scan.
Prior treatment with bortezomib.
Peripheral neuropathy of > Grade 2 as defined by CTCAE Version 3.0 (see Appendix II)
History of allergic reactions to compounds containing mannitol, bortezomib, conventional formulation of doxorubicin HCL or the components of DOXIL.
Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ³ 5 years.
NYHA Class III or IV heart disease. History of active unstable angina, congestive heart disease, serious uncontrolled cardiac arrhythmia or myocardial infarction within 6 months.

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Female patients who are pregnant or breastfeeding. Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
Known HIV or hepatitis A, B, or C positivity
Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
Any concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk, including, but not limited to, uncontrolled hypertension, uncontrolled diabetes, active uncontrolled infection, and/or acute chronic liver disease (i.e., hepatitis, cirrhosis).
No prior anti-myeloma therapy within 2 weeks of treatment initiation.

Trial locations and contacts

1 site in 1 country.

United States1 site

Weill Medical College of Cornell University
New York, New York, 10021

Other trials in United States

About this study

Official title: A Sequential Phase II Trial of the Combination of Bortezomib (VELCADE), Dexamethasone (DECADRON) and Pegylated Liposomal Doxorubicin (DOXIL) Followed by High Dose Cyclophosphamide in Multiple Myeloma Patients

PRIMARY STUDY OBJECTIVES

To evaluate the efficacy of the combination of bortezomib, dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide as a therapy for two different subsets of multiple myeloma patients:

Patients post first line therapy
Patients with relapsed/refractory disease who are bortezomib-naïve

To evaluate the safety of the combination of bortezomib and dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide as therapy for patients with multiple myeloma.

SECONDARY STUDY OBJECTIVES

To evaluate the role of the combination of bortezomib dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide on the ability to collect > 10 x 106 CD34+ cells/kg in < 7 collections (for both subsets of multiple myeloma patients).
To evaluate the survival of patients who receive the combination of bortezomib dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide (for both subsets of patients).

Conditions: Multiple Myeloma
Being tested: Bortezomib, dexamethasone, liposomal doxorubicin, cyclophoshamide, filgrastim
Medical subject headings: Multiple Myeloma

What participants receive

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

BortezomibDrug
Also called velcade
During Induction Phase (6 cycles): Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 During 21-day mobilization cycle (1 cycle): Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11
dexamethasoneDrug
Also called decadron
During Induction Phase (6 cycles): dexamethasone 40 mg on days 1-4, 8-11, and 15-18
liposomal doxorubicinDrug
If patients achieve less then a PR during the induction phase after 2 cycles, or less then a CR after 4 cycles: Liposomal doxorubicin was added at 30 mg/m2 on day 4 for the remaining cycles
cyclophoshamideDrug
Also called cytoxan
During the 21 day mobilization phase (1 cycle): cyclophosphamide at 3 g/m2 on day 8
filgrastimDrug
Also called neupogen
During the 21 day mobilization phase (1 cycle): 10 μg/kg/day for 10 consecutive days starting 24 hours after cyclophosphamide administration on day 9

Study groups in NCT00148317
Study group	Role	What they receive
Treatment Arm	Experimental	Not described Receives: Drug: Bortezomib; Drug: dexamethasone; Drug: liposomal doxorubicin; Drug: cyclophoshamide; Drug: filgrastim

What is being measured

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

Efficacy of Drug Combination as Therapy for Myeloma (Overall Response Rate)
Myeloma response criteria developed by Bladé et al. was used to categorize response.
Measured: Best response at any point during each respective study phase was collected - once after consolidation/prior to mobilization (approximately 6 cycles after start of treatment), and once after mobilization

Secondary outcomes (2)

Yield of CD34+ Stem Cells
This is the yield of CD34+ stem cells collection after high dose cyclophosphamide.
Measured: Occurred after mobilization, and prior to Stem cell transplant; a 7 day limit was imposed on stem cell collection
Progression Free Survival
Response was assessed using IMWG guidelines, which for progressive disease are as follows:
Increase of > 25% from lowest response value in any one or more of the following:
- 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)
- Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL
- Bone marrow plasma cell percentage; the absolute percentage must be > 10%
- Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
- Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder IF starting M protein component is > 5g/dL, then absolute increase of 1g is sufficient for progression.
Measured: Date of progression, assessed from start of trial to Final data cut off date (15 April 2011)

Timeline

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

Jun 2005Nov 2012

First posted7 Sep 2005 (estimated)
Study startJun 2005
Primary completionFeb 2011
Study completionNov 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Multiple MyelomaStudies of the same condition, open and under way.
More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Consolidation: All patients will receive 2 cycles of bortezomib (VEL) and dexamethasone (DEX). Patients who achieve a complete response after 2 cycles will receive 4 additional cycles of VEL/DEX before mobilization. Patients who do not achieve at least a partial response after 2 cycles will receive 4 more cycles of VEL/DEX plus DOXIL. Patients who achieve a partial response after 2 cycles on VEL/DEX, will continue this combination for 2 more cycles. Patients who achieve a complete response after 4 cycles will receive 2 additional cycles of VEL/DEX before mobilization. Patients who remain with a partial response after 4 cycles of VEL/DEX will receive 2 additional cycles of the combination of VEL/DEX plus DOXIL. Mobilization: Patients who complete 6 cycles of consolidation will proceed to mobilization. Patients will receive one cycle of VEL plus high dose CYTOXAN followed by G-CSF beginning 24 hours after CYTOXAN given for a total of 10 daily doses.
Masking: None (open label)
Enrolment: 38 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00148317
Sponsor's protocol ID: 0504007841
Status last verified: Jun 2017
First submitted: 2 Sep 2005
Last updated: 18 Jul 2017
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Multiple Myeloma trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Sequential Phase II Trial of the Combination of Bortezomib (VELCADE), Dexamethasone (DECADRON) and Pegylated Liposomal Doxorubicin (DOXIL) Followed by High Dose Cyclophosphamide in Multiple Myeloma Patients
ClinicalTrials.gov ID: NCT00148317
Acronym / sponsor ID: 0504007841
Conditions: Multiple Myeloma
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 38 participants (actual)
Lead sponsor: Weill Medical College of Cornell UniversityUniversity, hospital or other
Collaborators: Millennium Pharmaceuticals, Inc.
Study start: Jun 2005
Primary completion: Feb 2011 (actual)
Study completion: Nov 2012 (actual)
First posted: 7 Sep 2005 (estimated)
Results: Posted 18 Jul 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

PRIMARY STUDY OBJECTIVES

To evaluate the efficacy of the combination of bortezomib, dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide as a therapy for two different subsets of multiple myeloma patients:

Patients post first line therapy
Patients with relapsed/refractory disease who are bortezomib-naïve

To evaluate the safety of the combination of bortezomib and dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide as therapy for patients with multiple myeloma.

SECONDARY STUDY OBJECTIVES

To evaluate the role of the combination of bortezomib dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide on the ability to collect > 10 x 106 CD34+ cells/kg in < 7 collections (for both subsets of multiple myeloma patients).
To evaluate the survival of patients who receive the combination of bortezomib dexamethasone, with and without DOXIL, followed by high-dose cyclophosphamide (for both subsets of patients).

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Consolidation: All patients will receive 2 cycles of bortezomib (VEL) and dexamethasone (DEX). Patients who achieve a complete response after 2 cycles will receive 4 additional cycles of VEL/DEX before mobilization. Patients who do not achieve at least a partial response after 2 cycles will receive 4 more cycles of VEL/DEX plus DOXIL. Patients who achieve a partial response after 2 cycles on VEL/DEX, will continue this combination for 2 more cycles. Patients who achieve a complete response after 4 cycles will receive 2 additional cycles of VEL/DEX before mobilization. Patients who remain with a partial response after 4 cycles of VEL/DEX will receive 2 additional cycles of the combination of VEL/DEX plus DOXIL. Mobilization: Patients who complete 6 cycles of consolidation will proceed to mobilization. Patients will receive one cycle of VEL plus high dose CYTOXAN followed by G-CSF beginning 24 hours after CYTOXAN given for a total of 10 daily doses.

Arm	Type	Receives
Treatment Arm	Experimental	Drug: Bortezomib, Drug: dexamethasone, Drug: liposomal doxorubicin, Drug: cyclophoshamide, Drug: filgrastim

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (18 listed)

Subject must voluntarily sign and understand written informed consent.
Confirmed diagnosis of multiple myeloma as specified by the SWOG criteria and is detailed in Appendix I.
Measurable disease as defined the following:
Age > or = than 18 years at the time of signing the informed consent form.
Karnofsky performance status> or =70% (>60% if due to bony involvement of myeloma).

Key exclusion criteria (11 listed)

Patients with non-secretory MM (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine) unless measurable disease is available with imaging techniques such as MRI and PET scan.
Prior treatment with bortezomib.
Peripheral neuropathy of > Grade 2 as defined by CTCAE Version 3.0 (see Appendix II)
History of allergic reactions to compounds containing mannitol, bortezomib, conventional formulation of doxorubicin HCL or the components of DOXIL.
Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ³ 5 years.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BortezomibAlso: velcadeDuring Induction Phase (6 cycles): Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 During 21-day mobilization cycle (1 cycle): Bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11	Drug	Treatment Arm
dexamethasoneAlso: decadronDuring Induction Phase (6 cycles): dexamethasone 40 mg on days 1-4, 8-11, and 15-18	Drug	Treatment Arm
liposomal doxorubicinIf patients achieve less then a PR during the induction phase after 2 cycles, or less then a CR after 4 cycles: Liposomal doxorubicin was added at 30 mg/m2 on day 4 for the remaining cycles	Drug	Treatment Arm
cyclophoshamideAlso: cytoxanDuring the 21 day mobilization phase (1 cycle): cyclophosphamide at 3 g/m2 on day 8	Drug	Treatment Arm
filgrastimAlso: neupogenDuring the 21 day mobilization phase (1 cycle): 10 μg/kg/day for 10 consecutive days starting 24 hours after cyclophosphamide administration on day 9	Drug	Treatment Arm

Primary outcome

Efficacy of Drug Combination as Therapy for Myeloma (Overall Response Rate)
Time frame: Best response at any point during each respective study phase was collected - once after consolidation/prior to mobilization (approximately 6 cycles after start of treatment), and once after mobilization
Myeloma response criteria developed by Bladé et al. was used to categorize response.

2 secondary outcomes

Yield of CD34+ Stem Cells
Time frame: Occurred after mobilization, and prior to Stem cell transplant; a 7 day limit was imposed on stem cell collection
Progression Free Survival
Time frame: Date of progression, assessed from start of trial to Final data cut off date (15 April 2011)

Results and safety

Results posted to the registry on 18 Jul 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Overall Study	38	38

Primary outcome: Efficacy of Drug Combination as Therapy for Myeloma (Overall Response Rate)

Time frame: Best response at any point during each respective study phase was collected - once after consolidation/prior to mobilization (approximately 6 cycles after start of treatment), and once after mobilization. Number. Unit: participants

Measure	Treatment Arm - Post Mobilization n = 27	Treatment Arm - Responses Prior to Mobilization n = 38
Stringent Complete Response (sCR)	4	0
Complete Response (CR)	3	1
Very Good Partial response (VGPR)	6	1
Partial Response (PR)	13	2
Other Response (progression, stable disease, etc)	1	6

Population analysed: All 38 patients were treated with DoVeD consolidation therapy (Vel + DEX with or without DOXIL). Of the 38 patients enrolled, 27 proceeded to mobilization (11 did not undergo mobilization). Responses were assessed prior to mobilization (post DoVED), and again after mobilization, to see if mobilization improved patient response.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Safety was monitored throughout the study, from start of study until when patients were removed (for either progression, toxicity, or to get a HD-SCT, which occurred up to 1 year after start of treatment).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Arm (All Patients)	1 of 38 (2.6%)	38 of 38 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ruben Niesvizky, MD principal investigator

Weill Medical College of Cornell University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bortezomib, dexamethasone and liposomal doxorubicin in people with Multiple Myeloma, run by Weill Medical College of Cornell University 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 18 inclusion and 11 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 18 Jul 2017. 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 phase mean?

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 18 Jul 2017). 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?

Efficacy of Drug Combination as Therapy for Myeloma (Overall Response Rate) (time frame: Best response at any point during each respective study phase was collected - once after consolidation/prior to mobilization (approximately 6 cycles after start of treatment), and once after mobilization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00148317.

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 18 Jul 2017.