Multiple MyelomaPhase 2NCT00349778
High-Dose Sequential Therapy and Single Autologous Transplantation for Multiple Myeloma
A Phase 2 study testing Cyclophosphamide, Etoposide and Melphalan in people with Multiple Myeloma, run by Stanford University at 1 site in United States.
Trial summary
This study uses a sequence of high-dose chemotherapy drugs and a stem cell transplant to treat multiple myeloma. The study is being performed to evaluate the efficacy and side effects of treatment. Specifically, the study is designed to reduce the risk of interstitial pneumonitis. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Cyclophosphamide, Etoposide and Melphalan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2006to Apr 2010
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Stage II to III multiple myeloma, or progression after initial treatment of Stage I disease; early or relapsed
- Age 18 to 75 years.
- Pathology reviewed and the diagnosis confirmed at Stanford University Medical Center.
- Patients with amyloidosis may be eligible for this trial, with approval by the Principle Investigator.
- Patients must have a Karnofsky performance status > 70%.
- Aspartate aminotransferase (AST) must be < 2 x upper limit of normal (ULN)
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- Alanine aminotransferase (ALT) must be < 2 x ULN
- Total bilirubin < 2 mg/dL.
- Serum creatinine < 2.0 or 24-hour creatinine clearance ≥ 60 mL/min.
- Patients must be HIV-negative.
- Patients must provide signed, informed consent.
Who cannot join
- Severe psychological or medical illness
- Prior autologous hematopoietic cell transplantation
- Pregnant
- Lactating women
- Smoldering multiple myeloma,
- Monoclonal gammopathy of unknown significance or primary amyloidosis will be excluded from this study
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
This study uses a sequence of high-dose chemotherapy drugs and a stem cell transplant to treat multiple myeloma. The study is being performed to evaluate the efficacy and side effects of treatment. Specifically, the study is designed to reduce the risk of interstitial pneumonitis.
Read the detailed description
Analysis of 196 previously treated patients demonstrated a median event-free survival (EFS) of 36 months with a median overall survival of more than 6 years. The main toxicity of this therapy is related to carmustine-induced pneumonitis or interstitial pneumonitis (IP). This complication is related to the dose of carmustine. Institutional experience in myeloma patients using this dose of carmustine indicates an incidence of IP of34%.
There have been recent studies evaluating the role of tandem autologous transplants for patients with multiple myeloma. These trials were based upon the hypothesis that performing tandem high-dose therapy regimens would lead to increased tumor cell kill, decreased tumor burden and an improvement in overall survival. Our results with high-dose sequential therapy including the dose-intense carmustine/melphalan transplant demonstrates similar median EFS and overall survival (OS) when compared with the results of tandem transplant approaches.The proposed trial will continue to use a high-dose sequential transplant approach, however, we will use a reduced dose of carmustine which we expect to be associated with a lower incidence of IP.
- Conditions
- Multiple Myeloma
- Being tested
- Cyclophosphamide, Etoposide, Melphalan, Carmustine, 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.
CyclophosphamideDrug
Also called Cytoxan, Neosar
Cyclophosphamide as a white powder in 100 mg, 200 mg and 500 mg vials, to be dissolved in ~250 mL of saline or D5W and infused IV over 2 hours
EtoposideDrug
Also called Etopophos, VePesid, Toposar, VP-16
100 mg etoposide as 5 mL solution in clear ampules for injection.
MelphalanDrug
Also called Alkeran, L-PAM, L-Sarcolysin, Phenylalanine mustard
Melphalan as single-use glass vials of freeze-dried melphalan hydrochloride (equivalent to 50 mg of melphalan), to be reconstituted in 0.9% sodium chloride solution to not greater than 0.45 mg/mL, and administered within 1 hour of constitution.
CarmustineDrug
Also called BiCNU, BCNU
Carmustine as a powder for reconstitution in 100 mg vials, to be reconstituted with 3 mL sterile dehydrated ethanol and D5W. Carmustine should be dissolved in 500 mL of 5% dextrose in water (D5W) and infused IV over 2 hours.
FilgrastimDrug
Also called Neupogen, Granulocyte-colony stimulating factor (G-CSF)
Filgrastim in vials of 300 µg or 480 µg at a concentration of 300 µg/mL, to be given as a daily subcutaneous injection.
| Study group | Role | What they receive |
|---|---|---|
| High-Dose Sequential Therapy | Experimental | Cyclophosphamide + Etoposide + Melphalan + Carmustine with Filgrastim Receives: Drug: Cyclophosphamide; Drug: Etoposide; Drug: Melphalan; Drug: Carmustine; Drug: Filgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Pulmonary Toxicity
Pulmonary toxicity was assessed as the incidence of interstitial pneumonitis.
Measured: 2 years
Secondary outcomes (2)
Overall Participant Survival (OS)
Survival status was assessed 5 years after transplant.
Measured: 5 years
Number of Participants That Relapse After Autologous Transplantation
Relapse was measured as the number of patients who relapse after high-dose sequential therapy then autologous transplantation
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2006 (estimated)
- Study startAug 2006
- Primary completionApr 2009
- Study completionApr 2010
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Stanford 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
- Masking
- None (open label)
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sally Arai, Stanford University
- Investigators
- Sally Arai, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00349778
- Sponsor's protocol ID
- IRB-05704
- Other IDs
- 97115, BMT183
- Status last verified
- Nov 2017
- First submitted
- 5 Jul 2006
- Last updated
- 12 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chen AI, Negrin RS, McMillan A, Shizuru JA, Johnston LJ, Lowsky R, Miklos DB, Arai S, Weng WK, Laport GG, Stockerl-Goldstein K. Tandem chemo-mobilization followed by high-dose melphalan and carmustine with single autologous hematopoietic cell transplantation for multiple myeloma. Bone Marrow Transplant. 2012 Apr;47(4):516-21. doi: 10.1038/bmt.2011.106. Epub 2011 May 23.
PubMed 21602899
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-Dose Sequential Therapy and Single Autologous Transplantation for Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00349778
- Acronym / sponsor ID
- IRB-05704
- Conditions
- Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Aug 2006
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 10 Jul 2006 (estimated)
- Results
- Posted 12 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study uses a sequence of high-dose chemotherapy drugs and a stem cell transplant to treat multiple myeloma. The study is being performed to evaluate the efficacy and side effects of treatment. Specifically, the study is designed to reduce the risk of interstitial pneumonitis.
Detailed description
Analysis of 196 previously treated patients demonstrated a median event-free survival (EFS) of 36 months with a median overall survival of more than 6 years. The main toxicity of this therapy is related to carmustine-induced pneumonitis or interstitial pneumonitis (IP). This complication is related to the dose of carmustine. Institutional experience in myeloma patients using this dose of carmustine indicates an incidence of IP of34%.
There have been recent studies evaluating the role of tandem autologous transplants for patients with multiple myeloma. These trials were based upon the hypothesis that performing tandem high-dose therapy regimens would lead to increased tumor cell kill, decreased tumor burden and an improvement in overall survival. Our results with high-dose sequential therapy including the dose-intense carmustine/melphalan transplant demonstrates similar median EFS and overall survival (OS) when compared with the results of tandem transplant approaches.The proposed trial will continue to use a high-dose sequential transplant approach, however, we will use a reduced dose of carmustine which we expect to be associated with a lower incidence of IP.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| High-Dose Sequential Therapy | Experimental | Drug: Cyclophosphamide, Drug: Etoposide, Drug: Melphalan, Drug: Carmustine, Drug: FilgrastimCyclophosphamide + Etoposide + Melphalan + Carmustine with Filgrastim |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Stage II to III multiple myeloma, or progression after initial treatment of Stage I disease; early or relapsed
- Age 18 to 75 years.
- Pathology reviewed and the diagnosis confirmed at Stanford University Medical Center.
- Patients with amyloidosis may be eligible for this trial, with approval by the Principle Investigator.
- Patients must have a Karnofsky performance status > 70%.
Key exclusion criteria (6 listed)
- Severe psychological or medical illness
- Prior autologous hematopoietic cell transplantation
- Pregnant
- Lactating women
- Smoldering multiple myeloma,
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 |
|---|---|---|
| CyclophosphamideAlso: Cytoxan, NeosarCyclophosphamide as a white powder in 100 mg, 200 mg and 500 mg vials, to be dissolved in ~250 mL of saline or D5W and infused IV over 2 hours | Drug | High-Dose Sequential Therapy |
| EtoposideAlso: Etopophos, VePesid, Toposar, VP-16100 mg etoposide as 5 mL solution in clear ampules for injection. | Drug | High-Dose Sequential Therapy |
| MelphalanAlso: Alkeran, L-PAM, L-Sarcolysin, Phenylalanine mustardMelphalan as single-use glass vials of freeze-dried melphalan hydrochloride (equivalent to 50 mg of melphalan), to be reconstituted in 0.9% sodium chloride solution to not greater than 0.45 mg/mL, and administered within 1 hour of constitution. | Drug | High-Dose Sequential Therapy |
| CarmustineAlso: BiCNU, BCNUCarmustine as a powder for reconstitution in 100 mg vials, to be reconstituted with 3 mL sterile dehydrated ethanol and D5W. Carmustine should be dissolved in 500 mL of 5% dextrose in water (D5W) and infused IV over 2 hours. | Drug | High-Dose Sequential Therapy |
| FilgrastimAlso: Neupogen, Granulocyte-colony stimulating factor (G-CSF)Filgrastim in vials of 300 µg or 480 µg at a concentration of 300 µg/mL, to be given as a daily subcutaneous injection. | Drug | High-Dose Sequential Therapy |
Primary outcome
Number of Participants With Pulmonary Toxicity
Time frame: 2 years
Pulmonary toxicity was assessed as the incidence of interstitial pneumonitis.
2 secondary outcomes
Overall Participant Survival (OS)
Time frame: 5 years
Number of Participants That Relapse After Autologous Transplantation
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21602899Chen AI, Negrin RS, McMillan A, Shizuru JA, Johnston LJ, Lowsky R, Miklos DB, Arai S, Weng WK, Laport GG, Stockerl-Goldstein K. Tandem chemo-mobilization followed by high-dose melphalan and carmustine with single autologous hematopoietic cell transplantation for multiple myeloma. Bone Marrow Transplant. 2012 Apr;47(4):516-21. doi: 10.1038/bmt.2011.106. Epub 2011 May 23.
- Individual participant dataSharing planned: No
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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.
Sally Arai principal investigator
Stanford 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 Cyclophosphamide, Etoposide and Melphalan in people with Multiple Myeloma, run by Stanford 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 11 inclusion and 6 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 12 Dec 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 12 Dec 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?
Number of Participants With Pulmonary Toxicity (time frame: 2 years). 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 NCT00349778, 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 12 Dec 2017.