Multiple Myeloma and Plasma Cell NeoplasmPhase 1/2NCT00334932
Doxorubicin Hydrochloride Liposome, Melphalan, and Bortezomib in Treating Patients With Relapsed or Refractory Stage I, Stage II, or Stage III Multiple Myeloma
A Phase 1/2 study testing bortezomib, melphalan and pegylated liposomal doxorubicin hydrochloride in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Herbert Irving Comprehensive Cancer Center at 2 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- bortezomib, melphalan and pegylated liposomal doxorubicin hydrochloride
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2006to Jan 2010
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
DISEASE CHARACTERISTICS:
- Diagnosis of multiple myeloma
- Stage I, II, or III disease according to Durie-Salmon staging criteria
- Progressive disease, defined as one of the following:
- For secretory disease:
- A 25% increase in serum M-protein or Bence Jones protein (an absolute increase of 0.5 g/dL serum M-protein or ≥ 200 mg/24 hours of urine light chain excretion)
- For nonsecretory disease:
- Bone marrow biopsy with > 25% increase in plasma cells or an absolute increase of ≥ 10% over prior known level
- Development of new or worsening existing lytic bone lesions or soft tissue plasmacytomas
- Hypercalcemia (i.e., calcium > 11.5 mg/dL)
- Relapsed after complete response
- Must have received ≥ 2 of the following therapeutic regimens for multiple myeloma:
- Nonmyeloablative transplantation
- No significant graft-versus-host disease
- At least 30 days since prior immunosuppressive therapy (concurrent prednisone allowed provided dose is ≤ 10 mg daily)
- Mobilization with chemotherapy followed by either single or tandem autologous stem cell transplantation (considered 1 prior regimen)
- Mobilization with chemotherapy followed by autologous and subsequent nonmyeloablative allogeneic stem cell transplantation (considered 1 prior regimen)
- Any combination of drugs given concurrently (considered 1 prior regimen)
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy ≥ 3 months
- Absolute neutrophil count > 1,000/mm^3 (no colony-stimulating factors)
- Platelet count > 50,000/mm^3 (no transfusion support)
- Bilirubin ≤ 2.0 mg/dL
- AST ≤ 4 times upper limit of normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment
- No history of allergic reaction to compounds containing boron or mannitol
- No active uncontrolled viral (including HIV), bacterial, or fungal infection
- No motor or sensory neuropathy ≥ grade 2
- No myocardial infarction within the past 6 months
- No New York Heart Association class III or IV heart failure
- No uncontrolled angina
- No severe uncontrolled arrhythmia
- No acute ischemia by EKG
- LVEF ≥ 35% by MUGA (MUGA required in patients whose lifetime cumulative doxorubicin hydrochloride dose > 400 mg/m^2)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No grade III or IV toxicity due to previous antineoplastic therapy (except alopecia)
- At least 3 weeks since prior chemotherapy
- No prior doxorubicin HCl liposome, melphalan, and bortezomib as combination therapy (single or two-drug combinations of these are allowed)
- No concurrent corticosteroids (≤ 10 mg prednisone/day or equivalent allowed)
- No other concurrent chemotherapy
- No concurrent thalidomide
- No other concurrent investigational therapy
- No other concurrent antineoplastic treatment for multiple myeloma, including clarithromycin
- No concurrent radiation therapy
- No concurrent nonsteroidal anti-inflammatory agents
Trial locations and contacts
2 sites in 1 country.
United States2 sites, 2 recruiting
- Recruiting
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, 10032
Clinical Trials Office - Herbert Irving Comprehensive Cancer C, 212-305-8615
- Recruiting
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
Clinical Trials Office - UCSF Helen Diller Family Comprehensi, 877-827-3222
About this study
Official title: Phase I/II Study of Liposomal Doxorubicin (Doxil®)/ Melphalan/Bortezomib (Velcade®) in Relapsed/Refractory Multiple Myeloma
RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome and melphalan, 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. Giving doxorubicin hydrochloride liposome and melphalan together with bortezomib may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of doxorubicin hydrochloride liposome , melphalan, and bortezomib and to see how well they work in treating patients with relapsed or refractory stage I, stage II, or stage III multiple myeloma.
Read the detailed description
OBJECTIVES:
Primary
- Determine the safety and tolerability of doxorubicin HCl liposome, melphalan, and bortezomib in patients with relapsed or refractory stage I-III multiple myeloma.
- Determine the maximum tolerated dose (MTD) of this regimen in these patients.
Secondary
- Determine the overall response rate, including complete, near-complete, partial, and minimal response rate, in patients treated with this regimen.
- Determine the time to response, progression-free survival, and overall survival of patients treated with this regimen.
- Determine the toxic effects of this regimen at the MTD in these patients.
OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II study.
- Phase I: Patients receive doxorubicin HCl liposome IV over 30-60 minutes and melphalan IV over 30 minutes on day 1 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome, melphalan, and bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 4 of 6 patients experience dose-limiting toxicity after 2 courses of therapy.
- Phase II: Patients receive doxorubicin HCl liposome, melphalan, and bortezomib at the MTD as in phase I.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: Approximately 32 patients will be accrued for this study.
- Being tested
- bortezomib, melphalan, pegylated liposomal doxorubicin hydrochloride
- Keywords
- refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
melphalanDrug
pegylated liposomal doxorubicin hydrochlorideDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients experiencing treatment-related ≥ grade 3 hematologic or nonhematologic toxicity or treatment-related death (phase I)
Secondary outcomes (4)
Time to response (phase II)
Progression-free survival (phase II)
Overall survival (phase II)
Toxicities by NCI criteria (phase II)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2006 (estimated)
- Study startFeb 2006
- Primary completionJan 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple Myeloma and Plasma Cell NeoplasmStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Herbert Irving Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Ajai Chari, MD, Principal investigator, Herbert Irving Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00334932
- Sponsor's protocol ID
- CDR0000471769
- Other IDs
- CPMC-AAAB6443
- Status last verified
- Aug 2008
- First submitted
- 7 Jun 2006
- Last updated
- 10 Jan 2014
- Results posted
- No
Publications
Chari A, Kaplan L, Linker C, et al.: Phase I/II study of bortezomib in combination with liposomal doxorubicin and melphalan in relapsed or refractory multiple myeloma. [Abstract] Blood 106 (11): A-5182, 2005 .
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Liposomal Doxorubicin (Doxil®)/ Melphalan/Bortezomib (Velcade®) in Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00334932
- Acronym / sponsor ID
- CDR0000471769
- Keywords
- refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Herbert Irving Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2006
- Primary completion
- Jan 2010 (estimated)
- First posted
- 8 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome and melphalan, 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. Giving doxorubicin hydrochloride liposome and melphalan together with bortezomib may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of doxorubicin hydrochloride liposome , melphalan, and bortezomib and to see how well they work in treating patients with relapsed or refractory stage I, stage II, or stage III multiple myeloma.
Detailed description
OBJECTIVES:
Primary
- Determine the safety and tolerability of doxorubicin HCl liposome, melphalan, and bortezomib in patients with relapsed or refractory stage I-III multiple myeloma.
- Determine the maximum tolerated dose (MTD) of this regimen in these patients.
Secondary
- Determine the overall response rate, including complete, near-complete, partial, and minimal response rate, in patients treated with this regimen.
- Determine the time to response, progression-free survival, and overall survival of patients treated with this regimen.
- Determine the toxic effects of this regimen at the MTD in these patients.
OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II study.
- Phase I: Patients receive doxorubicin HCl liposome IV over 30-60 minutes and melphalan IV over 30 minutes on day 1 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome, melphalan, and bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 4 of 6 patients experience dose-limiting toxicity after 2 courses of therapy.
- Phase II: Patients receive doxorubicin HCl liposome, melphalan, and bortezomib at the MTD as in phase I.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: Approximately 32 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| bortezomib | Drug | – |
| melphalan | Drug | – |
| pegylated liposomal doxorubicin hydrochloride | Drug | – |
Primary outcome
Proportion of patients experiencing treatment-related ≥ grade 3 hematologic or nonhematologic toxicity or treatment-related death (phase I)
4 secondary outcomes
Time to response (phase II)
Progression-free survival (phase II)
Overall survival (phase II)
Toxicities by NCI criteria (phase II)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2014.
- Results publicationChari A, Kaplan L, Linker C, et al.: Phase I/II study of bortezomib in combination with liposomal doxorubicin and melphalan in relapsed or refractory multiple myeloma. [Abstract] Blood 106 (11): A-5182, 2005 .
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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.
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, United States
Ajai Chari, MD principal investigator
Herbert Irving Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing bortezomib, melphalan and pegylated liposomal doxorubicin hydrochloride in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Herbert Irving Comprehensive Cancer Center at 2 sites 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?
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: status not confirmed, as of the sponsor's last update on 10 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 2 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients experiencing treatment-related ≥ grade 3 hematologic or nonhematologic toxicity or treatment-related death (phase I). 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 NCT00334932, which also lists 1 linked publication.
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 10 Jan 2014.