Multiple MyelomaPhase 2NCT01548573
Tandem Auto Transplantation in Myeloma Patients With <12 Months of Prior Treatment
A Phase 2 study testing Dexamethasone, Tandem autologous stem cell transplant and Cisplatin in people with Multiple Myeloma, run by University of Iowa at 1 site in United States.
Trial summary
This study is designed to decrease toxicity associated with prior tandem transplant protocols by reducing the intensity of induction, consolidation and maintenance therapy, while increasing event-free survival by adding bortezomib (Velcade®), thalidomide, gemcitabine and carmustine to the transplant regimens to… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Dexamethasone, Tandem autologous stem cell transplant and Cisplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- May 2012to Aug 2014
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must have had a diagnosis of symptomatic MM, MM + amyloidosis, or POEMS (osteosclerotic myeloma: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) requiring treatment. Participants with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy. Note that study participants do not need to have active disease at the time of study entry, as participants may have received up to 12 months of prior chemotherapy, which might have induced a response.
- Protein criteria must be present (quantifiable M-component of IgG, IgA, IgD, or IgE and/or urinary kappa or lambda light chain, Bence-Jones protein, or Free Kappa Light Chain or Free Lambda Light Chain) in order to evaluate response. Non-secretory participants are eligible provided the participant has > 20% plasmacytosis OR multiple (>3) focal plasmacytomas or focal lesions on MRI.
- Participants must have received no more than 12 months of prior chemotherapy for this disease. Participants may have received prior radiotherapy provided approval has been obtained from the PI.
- Participants must not have had a prior transplant.
- Participants must be 18-80 years of age at the time of study entry.
- Ejection fraction by ECHO or MUGA of ≥ 40% performed.
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- Participants must have adequate pulmonary function studies, > 50% of predicted on mechanical aspects (FEV1, FVC) and diffusion capacity (DLCO) > 50% of predicted (adjusted for hemoglobin). If the participant is unable to complete pulmonary function tests due to disease related pain or condition, a participant may still be enrolled provided that the PI or enrolling investigator documents that the participant is a transplant candidate.
- Participants must have a creatinine < 3 mg/dl and a calculated creatinine clearance >30mL/min. The Cockroft-Gault equation may be used to obtain calculated creatinine clearance.
- Participants must have a performance status of 0-2 based on ECOG criteria. Participants with a poor performance status (3-4)based solely on bone pain will be eligible, provided there is documentation to verify this.
- Participants must sign the most current IRB-approved study ICF (Informed Consent Form).
Who cannot join
- Prior autologous or allogeneic transplant.
- Platelet count < 30 x 109/L, unless myeloma-related. If MM-related, the enrolling investigator must document this.
- > grade 3 neuropathy.
- Known hypersensitivity to bortezomib, boron, or mannitol.
- Uncontrolled diabetes.
- Recent (< 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias.
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- Participants must not have light chain deposition disease-related renal failure or creatinine >3 mg/dl.
- Participants must not have a concurrent malignancy unless it can be adequately treated by surgical, non-chemotherapeutic intervention. Participants may have a history of prior malignancy, provided that he/she has not had any treatment within 365 days of study entry AND that life expectancy exceeds 5 years at the time of study entry.
- Participants must not have life-threatening co-morbidities.
- Women of child-bearing potential must have a documented negative pregnancy test documented within one week of study entry. Women and men of reproductive potential may not participate unless they have agreed, by signing the study ICF, to use effective contraceptive method(s) as outlined in that form.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
About this study
Official title: Tandem Autotransplantation for Multiple Myeloma in Participants With Less Than 12 Months of Preceding Therapy, Incorporating Velcade (Bortezomib) With the Transplant Chemotherapy and During Maintenance
This study is designed to decrease toxicity associated with prior tandem transplant protocols by reducing the intensity of induction, consolidation and maintenance therapy, while increasing event-free survival by adding bortezomib (Velcade®), thalidomide, gemcitabine and carmustine to the transplant regimens to down-regulate the rescue of myeloma cells by the micro-environment and to prevent DNA repair post high-dose alkylating agent therapy. By reducing drug resistance, it is hoped that 3-year event-free survival will be increased significantly when compared to Total Therapy II. Additionally, participants will have the option of providing biospecimens for a sub-study evaluating gene expression profiling at specific timepoints to better understand drug-resistance in myeloma, and to determine whether there are genes or gene products in the resistant population that can be targeted by novel therapies.
Read the detailed description
This study is targeted towards patients who have been diagnosed with Multiple Myeloma, POEMS(Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), or myeloma plus amyloidosis and have had no more than 12 months of prior treatment. Furthermore, participants cannot have had a prior autologous or allogeneic transplant. The study schema consists of one round of induction chemotherapy, two transplants, one round of consolidation chemotherapy, and two years of maintenance treatment. This study design differs from its historical predecessors in the following manner:
- In contrast to Total Therapy II and III, which only allow enrollment of patients with one cycle or one month of treatment prior to enrollment, the proposed study allows enrollment of participants with up to 12 months of prior treatment.
- Induction therapy has been reduced to a single cycle.
- Bortezomib and thalidomide have been added to the transplant regimen.
- Carmustine is added to the second transplant.
- Gemcitabine is added to the second transplant regimen.
- Consolidation treatment has been reduced to a single cycle.
- The first year of maintenance consists of 12 28-day cycles of bortezomib,dexamethasone, and either thalidomide, lenalidomide, or cyclophoshamide. The second year of maintenance therapy consists of lenalidomide and dexamethasone.
- The novel agents thalidomide and bortezomib are not introduced upfront, but only with transplantation, consolidation, and maintenance.
- Conditions
- Multiple Myeloma
- Being tested
- Dexamethasone, Tandem autologous stem cell transplant, Cisplatin, Doxorubicin, Cyclophosphamide
- Keywords
- multiple myeloma, POEMS (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), amyloidosis, bone marrow transplant, autologous
- Medical subject headings
- Multiple Myeloma, Polyneuropathies, Endocrine System Diseases, Paraproteinemias, Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called Aeroseb-Dex, Decaderm, Decadron, DM
Given PO
Tandem autologous stem cell transplantProcedure or surgery
CisplatinDrug
Also called CACP, CDDP, CPDD, DDP
Given IV
DoxorubicinDrug
Also called ADM, ADR, Adria, Adriamycin PFS
Given IV
CyclophosphamideDrug
Also called CPM, CTX, Cytoxan, Endoxan
Given IV or PO
EtoposideDrug
Also called EPEG, VP-16, VP-16-213, Vepesid
Given IV
BortezomibDrug
Also called LDP 341, MLN341, VELCADE
Given IV
ThalidomideDrug
Also called Kevadon, Synovir, THAL, Thalomid
Given PO
MelphalanDrug
Also called Alkeran, CB-3025, L-PAM, L-phenylalanine mustard
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Tandem autologous stem cell transplant | Experimental | Induction: DPACE(dexamethasone,cisplatin,doxorubicin,cyclophosphamide,etoposide) chemotherapy plus stem cell collection. Additional stem cell collection and/or chemotherapy may be required.
After collection, participants will receive dexamethasone x 4 days every 14 days.
Transplant 1: The transplant preparative regimen will be bortezomib/thalidomide/dexamethasone/melphalan.
Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days.
Consolidation (if administered): VDT-PACE(bortezomib,dexamethasone,thalidomide,cisplatin,doxorubicin,cyclophosphamide, etoposide) Transplant 2: 8 weeks to 6 months after the first transplant, participants will have the second transplant Maintenance: Year 1- VTD (bortezomib, thalidomide, dexamethasone) cycles. Year 2 - VCD (bortezomib, cyclophosphamide, dexamethasone)cycles. Receives: Drug: Dexamethasone; Procedure: Tandem autologous stem cell transplant; Drug: Cisplatin; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Bortezomib; Drug: Thalidomide; Drug: Melphalan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-Free Survival (EFS)
To determine whether, in comparison to Total Therapy II, the median Event-Free Survival (EFS) can be increased from 4.8 years to 7.2 years, which represents an increase in median EFS of approximately 50%, based on an intent-to-treat analysis.
Measured: 8 years
Identification of Drug Resistant Genes
To determine whether repeated bone marrow samples analyzed for gene expression profiling (GEP) can identify genes related to drug resistance in myeloma. The drug resistant genes or the gene products might then be targeted specifically to eradicate myeloma cells surviving tandem transplantation.
Measured: 5 years
Secondary outcomes (2)
Number of Grade 3 Non-hematologic and Grade 4 Hematologic Serious Adverse Events Associated With the Addition of Bortezomib, Thalidomide, and Dexamethasone Into Autologous Transplant Regimens.
To determine whether bortezomib, thalidomide and dexamethasone with transplant 1 and velcade/gemcitabine with transplant 2 can be safely incorporated into well-tested pre-transplant regimens of high-dose melphalan and carmustine/melphalan in doses equivalent to the BEAM(BCNU, etoposide, arabinoside, melphalan)regimen. Treatment-related toxicities will be compared to those reported in the literature using similar intensive approaches.
Measured: 2 years
Overall Survival
To determine the median overall survival based on an intent-to-treat analysis, which should exceed 10 years, based on the projected 10-year survival of Total Therapy III, keeping in mind that participants are included in this protocol with up to 12 months of prior therapy.
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2012 (estimated)
- Study startMay 2012
- Primary completionJul 2013
- Study completionAug 2014
Why it stopped: Met study stopping rules
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 University of IowaThe 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Guido Tricot, University of Iowa
- Investigators
- Guido J Tricot, MD, PhD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01548573
- Sponsor's protocol ID
- 201202818
- Other IDs
- 7R01CA115399
- Status last verified
- May 2017
- First submitted
- 29 Feb 2012
- Last updated
- 14 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tandem Autotransplantation for Multiple Myeloma in Participants With Less Than 12 Months of Preceding Therapy, Incorporating Velcade (Bortezomib) With the Transplant Chemotherapy and During Maintenance
- ClinicalTrials.gov ID
- NCT01548573
- Acronym / sponsor ID
- 201202818
- Conditions
- Multiple Myeloma
- Keywords
- multiple myeloma, POEMS (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), amyloidosis, bone marrow transplant, autologous
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Met study stopping rules
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2012 (actual)
- Primary completion
- Jul 2013 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 8 Mar 2012 (estimated)
- Results
- Posted 14 Jun 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 is designed to decrease toxicity associated with prior tandem transplant protocols by reducing the intensity of induction, consolidation and maintenance therapy, while increasing event-free survival by adding bortezomib (Velcade®), thalidomide, gemcitabine and carmustine to the transplant regimens to down-regulate the rescue of myeloma cells by the micro-environment and to prevent DNA repair post high-dose alkylating agent therapy. By reducing drug resistance, it is hoped that 3-year event-free survival will be increased significantly when compared to Total Therapy II. Additionally, participants will have the option of providing biospecimens for a sub-study evaluating gene expression profiling at specific timepoints to better understand drug-resistance in myeloma, and to determine whether there are genes or gene products in the resistant population that can be targeted by novel therapies.
Detailed description
This study is targeted towards patients who have been diagnosed with Multiple Myeloma, POEMS(Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), or myeloma plus amyloidosis and have had no more than 12 months of prior treatment. Furthermore, participants cannot have had a prior autologous or allogeneic transplant. The study schema consists of one round of induction chemotherapy, two transplants, one round of consolidation chemotherapy, and two years of maintenance treatment. This study design differs from its historical predecessors in the following manner:
- In contrast to Total Therapy II and III, which only allow enrollment of patients with one cycle or one month of treatment prior to enrollment, the proposed study allows enrollment of participants with up to 12 months of prior treatment.
- Induction therapy has been reduced to a single cycle.
- Bortezomib and thalidomide have been added to the transplant regimen.
- Carmustine is added to the second transplant.
- Gemcitabine is added to the second transplant regimen.
- Consolidation treatment has been reduced to a single cycle.
- The first year of maintenance consists of 12 28-day cycles of bortezomib,dexamethasone, and either thalidomide, lenalidomide, or cyclophoshamide. The second year of maintenance therapy consists of lenalidomide and dexamethasone.
- The novel agents thalidomide and bortezomib are not introduced upfront, but only with transplantation, consolidation, and maintenance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tandem autologous stem cell transplant | Experimental | Drug: Dexamethasone, Procedure: Tandem autologous stem cell transplant, Drug: Cisplatin, Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: Etoposide, Drug: Bortezomib, Drug: Thalidomide, Drug: MelphalanInduction: DPACE(dexamethasone,cisplatin,doxorubicin,cyclophosphamide,etoposide) chemotherapy plus stem cell collection. Additional stem cell collection and/or chemotherapy may be required. After collection, participants will receive dexamethasone x 4 days every 14 days. Transplant 1: The transplant preparative regimen will be bortezomib/thalidomide/dexamethasone/melphalan. Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days. Consolidation (if administered): VDT-PACE(bortezomib,dexamethasone,thalidomide,cisplatin,doxorubicin,cyclophosphamide, etoposide) Transplant 2: 8 weeks to 6 months after the first transplant, participants will have the second transplant Maintenance: Year 1- VTD (bortezomib, thalidomide, dexamethasone) cycles. Year 2 - VCD (bortezomib, cyclophosphamide, dexamethasone)cycles. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Participants must have had a diagnosis of symptomatic MM, MM + amyloidosis, or POEMS (osteosclerotic myeloma: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) requiring treatment. Participants with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy. Note that study participants do not need to have active disease at the time of study entry, as participants may have received up to 12 months of prior chemotherapy, which might have induced a response.
- Protein criteria must be present (quantifiable M-component of IgG, IgA, IgD, or IgE and/or urinary kappa or lambda light chain, Bence-Jones protein, or Free Kappa Light Chain or Free Lambda Light Chain) in order to evaluate response. Non-secretory participants are eligible provided the participant has > 20% plasmacytosis OR multiple (>3) focal plasmacytomas or focal lesions on MRI.
- Participants must have received no more than 12 months of prior chemotherapy for this disease. Participants may have received prior radiotherapy provided approval has been obtained from the PI.
- Participants must not have had a prior transplant.
- Participants must be 18-80 years of age at the time of study entry.
Key exclusion criteria (10 listed)
- Prior autologous or allogeneic transplant.
- Platelet count < 30 x 109/L, unless myeloma-related. If MM-related, the enrolling investigator must document this.
- > grade 3 neuropathy.
- Known hypersensitivity to bortezomib, boron, or mannitol.
- Uncontrolled diabetes.
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 |
|---|---|---|
| DexamethasoneAlso: Aeroseb-Dex, Decaderm, Decadron, DMGiven PO | Drug | Tandem autologous stem cell transplant |
| Tandem autologous stem cell transplant | Procedure or surgery | Tandem autologous stem cell transplant |
| CisplatinAlso: CACP, CDDP, CPDD, DDPGiven IV | Drug | Tandem autologous stem cell transplant |
| DoxorubicinAlso: ADM, ADR, Adria, Adriamycin PFSGiven IV | Drug | Tandem autologous stem cell transplant |
| CyclophosphamideAlso: CPM, CTX, Cytoxan, EndoxanGiven IV or PO | Drug | Tandem autologous stem cell transplant |
| EtoposideAlso: EPEG, VP-16, VP-16-213, VepesidGiven IV | Drug | Tandem autologous stem cell transplant |
| BortezomibAlso: LDP 341, MLN341, VELCADEGiven IV | Drug | Tandem autologous stem cell transplant |
| ThalidomideAlso: Kevadon, Synovir, THAL, ThalomidGiven PO | Drug | Tandem autologous stem cell transplant |
| MelphalanAlso: Alkeran, CB-3025, L-PAM, L-phenylalanine mustardGiven IV | Drug | Tandem autologous stem cell transplant |
Primary outcome
Event-Free Survival (EFS)
Time frame: 8 years
To determine whether, in comparison to Total Therapy II, the median Event-Free Survival (EFS) can be increased from 4.8 years to 7.2 years, which represents an increase in median EFS of approximately 50%, based on an intent-to-treat analysis.
Identification of Drug Resistant Genes
Time frame: 5 years
To determine whether repeated bone marrow samples analyzed for gene expression profiling (GEP) can identify genes related to drug resistance in myeloma. The drug resistant genes or the gene products might then be targeted specifically to eradicate myeloma cells surviving tandem transplantation.
2 secondary outcomes
Number of Grade 3 Non-hematologic and Grade 4 Hematologic Serious Adverse Events Associated With the Addition of Bortezomib, Thalidomide, and Dexamethasone Into Autologous Transplant Regimens.
Time frame: 2 years
Overall Survival
Time frame: 10 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Guido J Tricot, MD, PhD principal investigator
University of Iowa
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 Dexamethasone, Tandem autologous stem cell transplant and Cisplatin in people with Multiple Myeloma, run by University of Iowa 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 10 inclusion and 10 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 14 Jun 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 14 Jun 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?
Event-Free Survival (EFS) (time frame: 8 years). The study lists 2 primary outcomes in all. 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 14 Jun 2017.