Multiple MyelomaEarly Phase 1NCT01537861
Filgrastim in Treating Patients With Bortezomib-, Carfilzomib-, or IMID-Refractory Multiple Myeloma
A Early Phase 1 study testing Filgrastim, Bortezomib and Carfilzomib in people with Multiple Myeloma, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Based on the pre-clinical data the investigators hypothesize that G-CSF treatment in patients with multiple myeloma will generate a 'hostile' bone marrow microenvironment for myeloma cells, depriving them of key support signals and rendering them more sensitive to chemotherapy. 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?
- Filgrastim, Bortezomib and Carfilzomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to Dec 2014
- Phase
- Early Phase 1
- 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
Who may be able to join
- Patient must have a confirmed diagnosis of multiple myeloma. The patient may be any stage of multiple myeloma. The patient may have received one or more lines of prior therapy (there is no limit to number of prior lines of therapy permissible).
- Patient must be ≥18 years of age
- Patient must be in active treatment with one of the following:
- twice-weekly bortezomib (on Days 1, 4, 8, and 11 of a 21-day cycle) with or without dexamethasone
- carfilzomib (on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle) with or without dexamethasone
- an IMID with or without dexamethasone daily on Days 1 to 21.
Show all 18Show fewer
- Patients being treated with bortezomib or carfilzomb may also be receiving an IMID or PO cyclophosphamide with the regimen.
- Patient must have shown stable or progressive disease on the current bortezomib-, carfilzomib-, or IMID-containing regimen with a measurable monoclonal protein component in the serum (at least 0.5 g/dl on electrophoresis or 0.05 g/dl [50mg/dl] on serum-free-light-chain). Patients who had an initial response on the current bortezomib-, carfilzomib-, or IMID-containing regimen but now have stable (plateaued) disease are eligible.
- Patient must have an ECOG performance status of 0 - 2
- Patient must be receiving concurrent treatment with bisphosphonates, with one dose occurring within 30 days prior to first day (Day -3) of protocol treatment
- Patient must have acceptable hematologic parameters, defined as:
- Absolute neutrophil count > 1000 cells/mm3
- Platelets ≥ 50,000 cells/mm3
- Hemoglobin ≥ 8 g/dl
- Patient must have adequate liver function, defined as:
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x upper limit of normal
- Total bilirubin < 2 x upper limit of normal
- Patient must be able to understand and willing to sign a written informed consent document
Who cannot join
- Patient must not be receiving any agents with known or suspected anti-myeloma activity (other than bortezomib, carfilzomib, dexamethasone, an IMID or PO cyclophosphamide, and bisphosphonates with the current regimen)
- Patient must not be actively using myeloid growth factors
- Patient must not have had any prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years
- Patient must not have any uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias, pulmonary disease, and symptomatic heart failure
- Patient must not have neuropathy ≥ grade 3 or painful neuropathy ≥ grade 2 (NCI CTCAE v 4.0)
- Patient must not have any known active infections requiring IV antibiotic, antiviral, or antifungal therapy
- Patient must not be pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Pilot Study of G-CSF to Disrupt the Bone Marrow Microenvironment in Bortezomib-, Carfilzomib-, or IMID-Refractory Multiple Myeloma
Based on the pre-clinical data the investigators hypothesize that G-CSF treatment in patients with multiple myeloma will generate a 'hostile' bone marrow microenvironment for myeloma cells, depriving them of key support signals and rendering them more sensitive to chemotherapy. The investigators therefore propose to do an initial pilot study 1) to explore the safety of the combination of G-CSF and bortezomib-, carfilzomib-, or IMID-based treatment regimens in patients with bortezomib-, carfilzomib-, or IMID-refractory myeloma and 2) to generate correlative data for a subsequent larger study looking at the combination.
- Conditions
- Multiple Myeloma
- Being tested
- Filgrastim, Bortezomib, Carfilzomib, Dexamethasone, Cyclophosphamide
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FilgrastimDrug
Also called G-CSF, Neupogen®, Granulocyte Colony-Stimulating Factor
BortezomibDrug
Also called Velcade®
CarfilzomibDrug
Also called Kyprolis®
DexamethasoneDrug
CyclophosphamideDrug
Also called Cytoxan
ThalidomideDrug
Also called Thalomid
LenalidomideDrug
Also called Revlimid
PomalidomideDrug
Also called Pomalyst
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Filgrastim 5 ug/kg from Day -3 to Day 10 of a single cycle.
Bortezomib will be given at the patient's current dose on Days 1, 4, 8, and 11 OR Carfilzomib will be given at the patient's current dose on Days 1, 2, 8, 9, 15, and 16 OR IMID will be given at the patient's current dose once daily on Days 1-21. Patients receiving an IMID (thalidomide, lenalidomide, or pomalidomide) as part of a bortezomib or carfilzomb regimen should continue the same scheduled as the current regimen.
Dexamethasone should be continued at the same dose and schedule as the patient's current regimen.
PO cyclophosphamide should be continued at the same dose and schedule as the patient's current regimen. Receives: Drug: Filgrastim; Drug: Bortezomib; Drug: Carfilzomib; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Thalidomide; Drug: Lenalidomide; Drug: Pomalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of the combination of G-CSF and bortezomib-, carfilzomib-, or IMID-based treatment regimens in patients with refractory multiple myeloma.
Number and grade of adverse events based on NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Measured: Up to 30 days after last treatment
Secondary outcomes (5)
Effects of G-CSF on bone marrow and bone marrow cytokine and chemokine levels. Including: Quantification of marrow osteoblasts and CAR cells, measurement of SDF-1 (CXCL12), IL-6, BAFF, assessment of myeloma cell proliferation and survival in bone marrow
Measured: 14 days after last drug treatment
Response rate as defined by the International Myeloma Working Group (IMWG) criteria
Measured: 14 days after last drug treatment
Overall survival duration of patients treated on study
Defined as the date of first dose of study drug to the date of death from any cause.
Measured: 1 year
Progression-free survival of patients treated on study
Defined as the interval from the date of first treatment to date of first documentation of disease progression.
Measured: 1 year
Duration of response of patients treated on study
Defined as the interval from the date of first documentation of response to the first documentation of disease progression.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2012 (estimated)
- Study startJun 2012
- Primary completionFeb 2014
- Study completionDec 2014
Why it stopped: Unexpected toxicity (2 early deaths)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ravi Vij, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01537861
- Sponsor's protocol ID
- 201204086
- Status last verified
- Jan 2015
- First submitted
- 15 Feb 2012
- Last updated
- 26 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of G-CSF to Disrupt the Bone Marrow Microenvironment in Bortezomib-, Carfilzomib-, or IMID-Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01537861
- Acronym / sponsor ID
- 201204086
- Conditions
- Multiple Myeloma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unexpected toxicity (2 early deaths)
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Jun 2012
- Primary completion
- Feb 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 23 Feb 2012 (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.
Based on the pre-clinical data the investigators hypothesize that G-CSF treatment in patients with multiple myeloma will generate a 'hostile' bone marrow microenvironment for myeloma cells, depriving them of key support signals and rendering them more sensitive to chemotherapy. The investigators therefore propose to do an initial pilot study 1) to explore the safety of the combination of G-CSF and bortezomib-, carfilzomib-, or IMID-based treatment regimens in patients with bortezomib-, carfilzomib-, or IMID-refractory myeloma and 2) to generate correlative data for a subsequent larger study looking at the combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Filgrastim, Drug: Bortezomib, Drug: Carfilzomib, Drug: Dexamethasone, Drug: Cyclophosphamide, Drug: Thalidomide, Drug: Lenalidomide, Drug: PomalidomideFilgrastim 5 ug/kg from Day -3 to Day 10 of a single cycle. Bortezomib will be given at the patient's current dose on Days 1, 4, 8, and 11 OR Carfilzomib will be given at the patient's current dose on Days 1, 2, 8, 9, 15, and 16 OR IMID will be given at the patient's current dose once daily on Days 1-21. Patients receiving an IMID (thalidomide, lenalidomide, or pomalidomide) as part of a bortezomib or carfilzomb regimen should continue the same scheduled as the current regimen. Dexamethasone should be continued at the same dose and schedule as the patient's current regimen. PO cyclophosphamide should be continued at the same dose and schedule as the patient's current regimen. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patient must have a confirmed diagnosis of multiple myeloma. The patient may be any stage of multiple myeloma. The patient may have received one or more lines of prior therapy (there is no limit to number of prior lines of therapy permissible).
- Patient must be ≥18 years of age
- Patient must be in active treatment with one of the following:
- Patient must have shown stable or progressive disease on the current bortezomib-, carfilzomib-, or IMID-containing regimen with a measurable monoclonal protein component in the serum (at least 0.5 g/dl on electrophoresis or 0.05 g/dl [50mg/dl] on serum-free-light-chain). Patients who had an initial response on the current bortezomib-, carfilzomib-, or IMID-containing regimen but now have stable (plateaued) disease are eligible.
- Patient must have an ECOG performance status of 0 - 2
Key exclusion criteria (7 listed)
- Patient must not be receiving any agents with known or suspected anti-myeloma activity (other than bortezomib, carfilzomib, dexamethasone, an IMID or PO cyclophosphamide, and bisphosphonates with the current regimen)
- Patient must not be actively using myeloid growth factors
- Patient must not have had any prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years
- Patient must not have any uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias, pulmonary disease, and symptomatic heart failure
- Patient must not have neuropathy ≥ grade 3 or painful neuropathy ≥ grade 2 (NCI CTCAE v 4.0)
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 |
|---|---|---|
| FilgrastimAlso: G-CSF, Neupogen®, Granulocyte Colony-Stimulating Factor | Drug | Arm 1 |
| BortezomibAlso: Velcade® | Drug | Arm 1 |
| CarfilzomibAlso: Kyprolis® | Drug | Arm 1 |
| Dexamethasone | Drug | Arm 1 |
| CyclophosphamideAlso: Cytoxan | Drug | Arm 1 |
| ThalidomideAlso: Thalomid | Drug | Arm 1 |
| LenalidomideAlso: Revlimid | Drug | Arm 1 |
| PomalidomideAlso: Pomalyst | Drug | Arm 1 |
Primary outcome
Safety of the combination of G-CSF and bortezomib-, carfilzomib-, or IMID-based treatment regimens in patients with refractory multiple myeloma.
Time frame: Up to 30 days after last treatment
Number and grade of adverse events based on NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
5 secondary outcomes
Effects of G-CSF on bone marrow and bone marrow cytokine and chemokine levels. Including: Quantification of marrow osteoblasts and CAR cells, measurement of SDF-1 (CXCL12), IL-6, BAFF, assessment of myeloma cell proliferation and survival in bone marrow
Time frame: 14 days after last drug treatment
Response rate as defined by the International Myeloma Working Group (IMWG) criteria
Time frame: 14 days after last drug treatment
Overall survival duration of patients treated on study
Time frame: 1 year
Progression-free survival of patients treated on study
Time frame: 1 year
Duration of response of patients treated on study
Time frame: 1 year
Results and safety
The study was stopped early (reason given: Unexpected toxicity (2 early deaths)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2015.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
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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.
Ravi Vij, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Filgrastim, Bortezomib and Carfilzomib in people with Multiple Myeloma, run by Washington University School of Medicine 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 7 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: stopped early, as of the sponsor's last update on 26 Jan 2015. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Unexpected toxicity (2 early deaths)). Results are not available in the source record.
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?
Safety of the combination of G-CSF and bortezomib-, carfilzomib-, or IMID-based treatment regimens in patients with refractory multiple myeloma. (time frame: Up to 30 days after last treatment). 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 26 Jan 2015.