Tandem Transplantation in Multiple Myeloma (MM) Patients With <12 Months of Prior Treatment

A Phase 2 study testing tandem autologous transplantation in people with Multiple Myeloma, run by Guido Tricot.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The two objectives of this study are: To increase the 2-year event-free survival from 55%, established with Total Therapy II (UARK 98-026), to 75% in myeloma patients with cytogenetic abnormalities, and from 80%, established with the Total Therapy II regimen, to 95% in myeloma patients without cytogenetic… 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?: tandem autologous transplantation
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 46 participants
Where: No sites listed yet
Study dates: Feb 2008to Apr 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 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients must have the diagnosis of active MM requiring treatment. Patients with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy.
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 patients are eligible provided the patient has > 20% plasmacytosis OR multiple (>3) focal plasmacytomas or focal lesions on MRI.
Patients must have received no more than 12 months of prior chemotherapy for this disease. Patients may have received prior radiotherapy provided approval has been obtained by the Principal Investigator.
Patients must be 18-75 years of age at the time of initial registration.
Ejection fraction by ECHO or MUGA ≥ 40% performed within 60 days prior to registration.
Patients must have adequate pulmonary function studies > 50% of predicted on mechanical aspects (FEV1, FVC) and diffusion capacity (DLCO) > 50% of predicted, within 60 days of registration. If the patient is unable to complete pulmonary function tests due to MM related pain or condition, exception may be granted if the principal investigator documents that the patient is a candidate for high dose therapy.

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Patients must have a creatinine < 3 mg/dl and a creatinine clearance >30mL/min
Patients must have a performance status of 0-2 based on SWOG criteria. Patients with a poor performance status (3-4), based solely on bone pain will be eligible.
All patients must be informed of the investigational nature of this study and must have signed an IRB-approved informed consent in accordance with institutional and federal guidelines.

Who cannot join

Platelet count < 30 x 109/L, unless myeloma-related.
Greater than a grade 2 peripheral neuropathy.
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.
Evidence of chronic obstructive or chronic restrictive pulmonary disease.

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Patients must not have light chain deposition disease-related renal failure or creatinine > 3 mg/dl.
Patients must not have prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment for one year prior to enrollment. Other cancers will only be acceptable if the patient's life expectancy exceeds five years.
Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection.
Pregnant or nursing women. Women of child-bearing potential must have a negative pregnancy test documented within one week of registration. Women and men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

About this study

Official title: Tandem Autotransplantation for Multiple Myeloma Patients With Less Than 12 Months of Preceding Therapy, Incorporating Bortezomib With the Transplant Chemotherapy and During Maintenance

The two objectives of this study are:

To increase the 2-year event-free survival from 55%, established with Total Therapy II (UARK 98-026), to 75% in myeloma patients with cytogenetic abnormalities, and from 80%, established with the Total Therapy II regimen, to 95% in myeloma patients without cytogenetic abnormalities.
To determine whether bortezomib, thalidomide, and dexamethasone can be safely incorporated with transplant 1 into the established pre-transplant regimen of high-dose melphalan (used in Total Therapy II) and whether Velcade and gemcitabine can be safely added to the transplant 2 high-dose chemotherapy regimen of combination melphalan and BCNU.

Read the detailed description

This study is targeted towards patients who have been diagnosed with Multiple Myeloma and have had no prior autologous or allogeneic transplant. Furthermore, only up to 12 months of prior treatment are allowed in this patient population. 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 at most one cycle or one month of treatment prior to enrollment, the proposed study allows enrollment of patients with up to 12 months of prior treatment. No statistically significant difference in outcome between patients with one or no cycle of preceding therapy and those with up to 12 months of prior therapy. This should allow enrollment of significantly more myeloma patients.
Induction therapy has been reduced to a single cycle.
Bortezomib and thalidomide have been added to the transplant regimen.
BCNU is added to the second transplant to high dose melphalan.
Gemcitabine is added to the second transplant regimen.
Consolidation treatment has been reduced to a single cycle.
The first year of maintenance is with bortezomib, thalidomide and dexamethasone, and the second year of maintenance therapy consists of dexamethasone only.
The novel agents thalidomide and bortezomib are not introduced upfront, but only with transplantation and maintenance.

Conditions: Multiple Myeloma
Being tested: tandem autologous transplantation
Keywords: Multiple Myeloma, 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.

tandem autologous transplantationCombination product
DPACE: dexamethasone 20 mg days 1-4 and 8-11, cisplatin 10 mg/m2 days 1-4, Adriamycin 10 mg/m2 days 1-4, cyclophosphamide 400 mg/m2 days 1-4, etoposide 40 mg/m2 days 1-4.
Transplant 1: Dexamethasone 20 mg days -4 to -1 and +2 to +5. Velcade 1mg/m2 on days -4,-1, +2, and +5. Thalidomide 100mg on day -4 to day +5. Melphalan, 100 mg/m2 on days -4 and -1.
Transplant 2: Dexamethasone 20 mg on days -4 to -1 and +2 to +5. BCNU 300mg/m2 on day -4. Melphalan 140 mg/m2 on day -1. Velcade 1mg/m2 on days -4, -1, +2, +5. Gemcitabine 1000 mg/m2 on days -4 + -1.
Maintenance year 1: Bortezomib 1.0 mg/m2 on days 1, 4, 15,18 every cycle. Thalidomide, 100 mg . Dexamethasone,20 mg,on days 1-4 \& 15-18 every cycle.
Maintenance year 2: Dexamethasone, 20 mg,days 1-4 every cycle.

Study groups in NCT00670631
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: Combination Product: tandem autologous transplantation

What is being measured

The primary outcome is the main question the study is designed to answer.

To Determine Whether, in Comparison to TT II, the Median EFS Can be Increased From 4.8 Years to 6.2 Years, Which Represents an Increase in Median EFS of Approximately 30%
Measured: After enrollment of 204 subjects is completed
In Assessing Patient Safety, we Will Examine Treatment Toxicity Related Mortality and SAEs. Historical Study Results Indicate That a Mortality Rate of Greater Than 10% is Not Acceptable in This Population, Nor is an SAE Rate of Greater Than 15%.
Measured: Interim analyses for safety will be performed after 20, 100, 200, and 300 patients have been enrolled.

Secondary outcomes (1)

Overall Survival Will be Compared to a Historical Control (UARK 98-026, TT2)as a Secondary Outcome.
Measured: After 204 patients have been enrolled

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2008Apr 2014

First posted2 May 2008 (estimated)
Study startFeb 2008
Primary completionMay 2012
Study completionApr 2014

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.
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
Model description: Induction- Tandem Transplants with VTD-MEL and gemcitabine, BCNU, melphalan, velcade and dexamethasone- Maintenance therapy
Masking: None (open label)
Enrolment: 46 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00670631
Sponsor's protocol ID: 25009
Other IDs: 7R01CA115399
Status last verified: Aug 2017
First submitted: 3 Apr 2008
Last updated: 31 Aug 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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)
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All Multiple Myeloma trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Tandem Autotransplantation for Multiple Myeloma Patients With Less Than 12 Months of Preceding Therapy, Incorporating Bortezomib With the Transplant Chemotherapy and During Maintenance
ClinicalTrials.gov ID: NCT00670631
Acronym / sponsor ID: 25009
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma, myeloma
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 46 participants (actual)
Lead sponsor: Guido TricotUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: Feb 2008
Primary completion: May 2012 (actual)
Study completion: Apr 2014 (actual)
First posted: 2 May 2008 (estimated)
Results: Posted 31 Aug 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The two objectives of this study are:

To increase the 2-year event-free survival from 55%, established with Total Therapy II (UARK 98-026), to 75% in myeloma patients with cytogenetic abnormalities, and from 80%, established with the Total Therapy II regimen, to 95% in myeloma patients without cytogenetic abnormalities.
To determine whether bortezomib, thalidomide, and dexamethasone can be safely incorporated with transplant 1 into the established pre-transplant regimen of high-dose melphalan (used in Total Therapy II) and whether Velcade and gemcitabine can be safely added to the transplant 2 high-dose chemotherapy regimen of combination melphalan and BCNU.

Detailed description

In contrast to Total Therapy II and III, which only allow enrollment of patients with at most one cycle or one month of treatment prior to enrollment, the proposed study allows enrollment of patients with up to 12 months of prior treatment. No statistically significant difference in outcome between patients with one or no cycle of preceding therapy and those with up to 12 months of prior therapy. This should allow enrollment of significantly more myeloma patients.
Induction therapy has been reduced to a single cycle.
Bortezomib and thalidomide have been added to the transplant regimen.
BCNU is added to the second transplant to high dose melphalan.
Gemcitabine is added to the second transplant regimen.
Consolidation treatment has been reduced to a single cycle.
The first year of maintenance is with bortezomib, thalidomide and dexamethasone, and the second year of maintenance therapy consists of dexamethasone only.
The novel agents thalidomide and bortezomib are not introduced upfront, but only with transplantation and maintenance.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Induction- Tandem Transplants with VTD-MEL and gemcitabine, BCNU, melphalan, velcade and dexamethasone- Maintenance therapy

Arm	Type	Receives
Tandem autologous stem cell transplant	Experimental	Combination Product: tandem autologous transplantationInduction: 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 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Patients must have the diagnosis of active MM requiring treatment. Patients with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy.
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 patients are eligible provided the patient has > 20% plasmacytosis OR multiple (>3) focal plasmacytomas or focal lesions on MRI.
Patients must have received no more than 12 months of prior chemotherapy for this disease. Patients may have received prior radiotherapy provided approval has been obtained by the Principal Investigator.
Patients must be 18-75 years of age at the time of initial registration.
Ejection fraction by ECHO or MUGA ≥ 40% performed within 60 days prior to registration.

Key exclusion criteria (10 listed)

Platelet count < 30 x 109/L, unless myeloma-related.
Greater than a grade 2 peripheral neuropathy.
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.

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
tandem autologous transplantationDPACE: dexamethasone 20 mg days 1-4 and 8-11, cisplatin 10 mg/m2 days 1-4, Adriamycin 10 mg/m2 days 1-4, cyclophosphamide 400 mg/m2 days 1-4, etoposide 40 mg/m2 days 1-4. Transplant 1: Dexamethasone 20 mg days -4 to -1 and +2 to +5. Velcade 1mg/m2 on days -4,-1, +2, and +5. Thalidomide 100mg on day -4 to day +5. Melphalan, 100 mg/m2 on days -4 and -1. Transplant 2: Dexamethasone 20 mg on days -4 to -1 and +2 to +5. BCNU 300mg/m2 on day -4. Melphalan 140 mg/m2 on day -1. Velcade 1mg/m2 on days -4, -1, +2, +5. Gemcitabine 1000 mg/m2 on days -4 + -1. Maintenance year 1: Bortezomib 1.0 mg/m2 on days 1, 4, 15,18 every cycle. Thalidomide, 100 mg . Dexamethasone,20 mg,on days 1-4 \& 15-18 every cycle. Maintenance year 2: Dexamethasone, 20 mg,days 1-4 every cycle.	Combination product	Tandem autologous stem cell transplant

Primary outcome

To Determine Whether, in Comparison to TT II, the Median EFS Can be Increased From 4.8 Years to 6.2 Years, Which Represents an Increase in Median EFS of Approximately 30%
Time frame: After enrollment of 204 subjects is completed
In Assessing Patient Safety, we Will Examine Treatment Toxicity Related Mortality and SAEs. Historical Study Results Indicate That a Mortality Rate of Greater Than 10% is Not Acceptable in This Population, Nor is an SAE Rate of Greater Than 15%.
Time frame: Interim analyses for safety will be performed after 20, 100, 200, and 300 patients have been enrolled.

1 secondary outcome

Overall Survival Will be Compared to a Historical Control (UARK 98-026, TT2)as a Secondary Outcome.
Time frame: After 204 patients have been enrolled

Results and safety

Results posted to the registry on 31 Aug 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tandem Autologous Stem Cell Transplant	0	0

Primary outcome: To Determine Whether, in Comparison to TT II, the Median EFS Can be Increased From 4.8 Years to 6.2 Years, Which Represents an Increase in Median EFS of Approximately 30%

Time frame: After enrollment of 204 subjects is completed

Population analysed: Data not available. Study conducted at University of Utah. Upon PI leaving Utah and coming to the University of Iowa, record NCT00670631 was transferred to Iowa by ClinicalTrials.gov staff. No research activities under NCT00670631 were conducted at Iowa. PRS staff at Iowa and Utah have corresponded and neither party (including PI) have the data.

Primary outcome: In Assessing Patient Safety, we Will Examine Treatment Toxicity Related Mortality and SAEs. Historical Study Results Indicate That a Mortality Rate of Greater Than 10% is Not Acceptable in This Population, Nor is an SAE Rate of Greater Than 15%.

Time frame: Interim analyses for safety will be performed after 20, 100, 200, and 300 patients have been enrolled.

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tandem Autologous Stem Cell Transplant	0 of 0	0 of 0	0

Limitations and caveats (from the sponsor): Data not available. Study conducted at Utah. Upon PI leaving \& coming to Iowa, record was transferred to IA by ClinicalTrials.gov. No research activities under NCT00670631 were conducted at IA. PRS staff have corresponded and neither party have data.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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.

Guido J Tricot, MD, PhD principal investigator

University of Iowa

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing tandem autologous transplantation in people with Multiple Myeloma, run by Guido Tricot.

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 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: finished, as of the sponsor's last update on 31 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

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 31 Aug 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?

To Determine Whether, in Comparison to TT II, the Median EFS Can be Increased From 4.8 Years to 6.2 Years, Which Represents an Increase in Median EFS of Approximately 30% (time frame: After enrollment of 204 subjects is completed). 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?

On the ClinicalTrials.gov record for NCT00670631.

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 31 Aug 2017.