Multiple MyelomaPhase 2NCT00307086
Bortezomib Followed by High-Dose Melphalan and Bortezomib as Conditioning Regimen for Tandem Stem Cell Transplants
A Phase 2 study testing Bortezomib, Melphalan and PBSCT in people with Multiple Myeloma and Plasma Cell Leukemia, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The primary objectives of this study are to: To determine the maximum tolerated dose (MTD) of bortezomib in combination with high-dose melphalan as a conditioning regimen. To determine the safety, tolerability, and response rates of bortezomib given in combination with high-dose melphalan, as a conditioning regimen… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, Plasma Cell Leukemia
- What is being tested?
- Bortezomib, Melphalan and PBSCT
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to Mar 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
- 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Female is either post-menopausal or 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.
- Male agrees to use an acceptable method for contraception for the duration of the study.
- Multiple Myeloma Criteria:
- Patients with primary refractory disease (those failing to achieve at least a partial response, as defined by the Bladé multiple myeloma response criteria, after first-line (induction) therapy). A partial response will be defined as the following: ≥50% reduction in the level of the serum monoclonal paraprotein, maintained for a minimum of 6 weeks, Reduction in 24-hour urinary light chain excretion either by ≥ 90% or to < 200 mg, maintained for a minimum of 6 weeks. For patients with non-secretory myeloma only, ≥ 50% reduction in plasma cells in a bone marrow aspirate and biopsy, maintained for a minimum of 6 weeks, ≥ 50% reduction in the size of soft tissue plasmacytomas (by radiography or physical examination). No increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response).
- Patients with plasma cell leukemia, either newly diagnosed or previously treated.
Show all 9Show fewer
- Patients greater than or equal to 18 years of age are eligible.
- Patients must have a histologically confirmed diagnosis by a pathologic review at the H. Lee Moffitt Cancer Center and Research Institute.
- Patients must have undergone a complete psychosocial evaluation and have been considered capable of compliance.
Who cannot join
- Patient has a platelet count of <30× 10^9/L within 14 days before enrollment.
- Patient has an absolute neutrophil count of <1.0 × 10^9/L within 14 days before enrollment.
- Patient has a serum creatinine of greater than 2.0 mg/dL OR a creatinine clearance of less than 40 ml/minute within 14 days before enrollment. Creatinine clearance can be measured or calculated.
- Has >Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
- Patient has hypersensitivity to bortezomib, boron or mannitol.
Show all 18Show fewer
- Female is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for postmenopausal or surgically sterilized women.
- Patient has received other investigational drugs with 14 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Patients with a DLCO less than 50% (adjusted) of normal or with symptomatic obstructive or restrictive lung disease are ineligible.
- Patients with renal dysfunction secondary to multiple myeloma may be enrolled at the discretion of the principal investigator. However, patients on hemodialysis or peritoneal dialysis are ineligible.
- Patients with a total bilirubin greater than 2.0 mg/dL and SGOT or SGPT greater than two and a half times normal (unless due to primary malignancy), or a history of severe hepatic dysfunction are ineligible.
- Patients with active infections are ineligible.
- Patients who are HIV positive are ineligible.
- Patients with active leptomeningeal involvement are ineligible. Patients with a history of previous CSF tumor involvement without symptoms or signs are eligible provided the CSF is now free of disease on lumbar puncture, and MRI of the brain shows no tumor involvement. Patients with severe symptomatic central nervous system (CNS) disease of any etiology are ineligible.
- Patients with uncontrolled insulin-dependent diabetes mellitus or uncompensated major thyroid or adrenal dysfunction are ineligible.
- Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2 are ineligible.
- Patients with an ECOG performance status of 2 to 3, secondary to bone pain, may be enrolled at the discretion of the institutional investigator(s).
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
About this study
Official title: An Evaluation of Bortezomib (VelcadeR ) Followed by High-Dose Melphalan and Bortezomib (VelcadeR) as Conditioning Regimen for Tandem Peripheral Blood Stem Cell Transplants in Patients With Primary Refractory Multiple Myeloma and Plasma Cell Leukemia
The primary objectives of this study are to:
- To determine the maximum tolerated dose (MTD) of bortezomib in combination with high-dose melphalan as a conditioning regimen.
- To determine the safety, tolerability, and response rates of bortezomib given in combination with high-dose melphalan, as a conditioning regimen, for tandem transplants in patients with primary refractory multiple myeloma or plasma cell leukemia.
Read more
The secondary objectives of this study are to:
- To determine gene expression profiles (pharmacogenomics) and perform RTPCR for Fanconi anemia pathway genes, prior to and after treatment with bortezomib, in patients with primary refractory multiple myeloma and plasma cell leukemia and correlate profiles with responses to treatment.
- To determine the time to disease progression and overall survival in patients with primary refractory multiple myeloma and plasma cell leukemia treated with bortezomib followed by tandem autologous transplantation
- To determine the response rates of 2 cycles of bortezomib in patients with primary refractory multiple myeloma or plasma cell leukemia
Read the detailed description
Patients with primary refractory multiple myeloma or plasma cell leukemia either newly diagnosed or previously treated will receive 2-cycles of standard dose bortezomib followed by high-dose melphalan and bortezomib as a conditioning regimen prior to a tandem autologous peripheral blood stem cell transplantation (PBSCT). Following treatment with two cycles of standard dose bortezomib, sequential cohorts of patients will be given escalating bortezomib doses combined with standard and constant conditioning regimen doses of melphalan. Once the MTD of bortezomib is reached, that dose will be administered in combination with melphalan as conditioning prior to PBSCT.
- Conditions
- Multiple Myeloma, Plasma Cell Leukemia
- Being tested
- Bortezomib, Melphalan, PBSCT
- Medical subject headings
- Multiple Myeloma, Leukemia, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
the maximum tolerated dose (MTD) of bortezomib in combination with high-dose melphalan as a conditioning regimen for autologous stem cell transplant
MelphalanDrug
Also called Alkeran(R)
Day -4 melphalan 100 mg/m2 intravenously over 30 minutes, Day -3 melphalan 100 mg/m2 intravenously over 30 minutes
PBSCTProcedure or surgery
Also called peripheral blood stem cell transplant (PBSCT)
PBSCT #1 Day 0 PBSCT #2 Day 0 (approx 90 days =/- 15 days after PBSCT #1)
| Study group | Role | What they receive |
|---|---|---|
| Autologous PBSCT | Other | bortezomib in combination with high-dose melphalan as a conditioning regimen for autologous peripheral blood stem cell transplant (PBSCT) Receives: Drug: Bortezomib; Drug: Melphalan; Procedure: PBSCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Median overall survival after first peripheral blood stem cell transplant (PBSCT).
Measured: 40 months post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2006 (estimated)
- Study startJun 2005
- Primary completionMar 2012
- Study completionMar 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 H. Lee Moffitt Cancer Center and Research InstituteThe 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
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Melissa Alsina, MD, Principal investigator, H. Lee Moffitt Cancer Center and Research InstituteTodd Alekshun, MD, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00307086
- Sponsor's protocol ID
- MCC-14184
- Other IDs
- X05174
- Status last verified
- Aug 2013
- First submitted
- 23 Mar 2006
- Last updated
- 6 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Evaluation of Bortezomib (VelcadeR ) Followed by High-Dose Melphalan and Bortezomib (VelcadeR) as Conditioning Regimen for Tandem Peripheral Blood Stem Cell Transplants in Patients With Primary Refractory Multiple Myeloma and Plasma Cell Leukemia
- ClinicalTrials.gov ID
- NCT00307086
- Acronym / sponsor ID
- MCC-14184
- Conditions
- Multiple Myeloma, Plasma Cell Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Jun 2005
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 27 Mar 2006 (estimated)
- Results
- Posted 24 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objectives of this study are to:
- To determine the maximum tolerated dose (MTD) of bortezomib in combination with high-dose melphalan as a conditioning regimen.
- To determine the safety, tolerability, and response rates of bortezomib given in combination with high-dose melphalan, as a conditioning regimen, for tandem transplants in patients with primary refractory multiple myeloma or plasma cell leukemia.
The secondary objectives of this study are to:
- To determine gene expression profiles (pharmacogenomics) and perform RTPCR for Fanconi anemia pathway genes, prior to and after treatment with bortezomib, in patients with primary refractory multiple myeloma and plasma cell leukemia and correlate profiles with responses to treatment.
- To determine the time to disease progression and overall survival in patients with primary refractory multiple myeloma and plasma cell leukemia treated with bortezomib followed by tandem autologous transplantation
- To determine the response rates of 2 cycles of bortezomib in patients with primary refractory multiple myeloma or plasma cell leukemia
Detailed description
Patients with primary refractory multiple myeloma or plasma cell leukemia either newly diagnosed or previously treated will receive 2-cycles of standard dose bortezomib followed by high-dose melphalan and bortezomib as a conditioning regimen prior to a tandem autologous peripheral blood stem cell transplantation (PBSCT). Following treatment with two cycles of standard dose bortezomib, sequential cohorts of patients will be given escalating bortezomib doses combined with standard and constant conditioning regimen doses of melphalan. Once the MTD of bortezomib is reached, that dose will be administered in combination with melphalan as conditioning prior to PBSCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Autologous PBSCT | Other | Drug: Bortezomib, Drug: Melphalan, Procedure: PBSCTbortezomib in combination with high-dose melphalan as a conditioning regimen for autologous peripheral blood stem cell transplant (PBSCT) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
- Female is either post-menopausal or 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.
- Male agrees to use an acceptable method for contraception for the duration of the study.
- Multiple Myeloma Criteria:
- Patients with primary refractory disease (those failing to achieve at least a partial response, as defined by the Bladé multiple myeloma response criteria, after first-line (induction) therapy). A partial response will be defined as the following: ≥50% reduction in the level of the serum monoclonal paraprotein, maintained for a minimum of 6 weeks, Reduction in 24-hour urinary light chain excretion either by ≥ 90% or to < 200 mg, maintained for a minimum of 6 weeks. For patients with non-secretory myeloma only, ≥ 50% reduction in plasma cells in a bone marrow aspirate and biopsy, maintained for a minimum of 6 weeks, ≥ 50% reduction in the size of soft tissue plasmacytomas (by radiography or physical examination). No increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response).
Key exclusion criteria (18 listed)
- Patient has a platelet count of <30× 10^9/L within 14 days before enrollment.
- Patient has an absolute neutrophil count of <1.0 × 10^9/L within 14 days before enrollment.
- Patient has a serum creatinine of greater than 2.0 mg/dL OR a creatinine clearance of less than 40 ml/minute within 14 days before enrollment. Creatinine clearance can be measured or calculated.
- Has >Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
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: Velcadethe maximum tolerated dose (MTD) of bortezomib in combination with high-dose melphalan as a conditioning regimen for autologous stem cell transplant | Drug | Autologous PBSCT |
| MelphalanAlso: Alkeran(R)Day -4 melphalan 100 mg/m2 intravenously over 30 minutes, Day -3 melphalan 100 mg/m2 intravenously over 30 minutes | Drug | Autologous PBSCT |
| PBSCTAlso: peripheral blood stem cell transplant (PBSCT)PBSCT #1 Day 0 PBSCT #2 Day 0 (approx 90 days =/- 15 days after PBSCT #1) | Procedure or surgery | Autologous PBSCT |
Primary outcome
Overall Survival (OS)
Time frame: 40 months post transplant
Median overall survival after first peripheral blood stem cell transplant (PBSCT).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- H Lee Moffitt Cancer Center \& Research Institute websiteLink provided by the sponsor.
Related trials for Multiple Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
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.
Melissa Alsina, MD principal investigator
H. Lee Moffitt Cancer Center and Research Institute
Todd Alekshun, MD principal investigator
H. Lee Moffitt Cancer Center and Research Institute
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, Melphalan and PBSCT in people with Multiple Myeloma and Plasma Cell Leukemia, 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 9 inclusion and 18 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 6 Mar 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 24 Oct 2013). 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?
Overall Survival (OS) (time frame: 40 months post transplant). 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 6 Mar 2017.