Multiple MyelomaPhase 1/2NCT00483262

Combination CCI-779 (Temsirolimus) and Bortezomib (Velcade) in Relapsed and/or Relapsed/Refractory Multiple Myeloma

A Phase 1/2 study testing CCI-779 and Bortezomib in people with Multiple Myeloma, run by Dana-Farber Cancer Institute at 3 sites in United States.

Completed

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

Official record

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Trial summary

The purpose of this research study is to determine the safety of CCI-779 (Temsirolimus) and bortezomib (Velcade), and the highest dose of this drug that can be given to people safely. We will also be looking at how the combination of the two drugs may work against multiple myeloma. 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?: CCI-779 and Bortezomib
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 63 participants
Where: 3 sitesUnited States
Study dates: May 2007to Feb 2012
Phase: Phase 1/2
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

18 years of age or older
Must have received prior therapy for their myeloma and have relapsed and/or relapsed/refractory multiple myeloma
Monoclonal protein in the serum of greater than or equal to 1 gm/dL or monoclonal light chain in the urine protein electrophoresis of greater than or equal to 200mg/24 hours, or measurable light chains by free light chain assay of greater than or equal to 10mg/dl, or measurable plasmacytoma
ECOG Performance Status 0, 1 or 2
Laboratory values as outlined in the protocol

Who cannot join

Uncontrolled infection
Cytotoxic chemotherapy less than 2 weeks, or biologic therapy less than 2 weeks, or corticosteroids less than 2 weeks prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than myeloma.
Pregnant or nursing women
Men or women of childbearing potential who are unwilling to employ adequate contraception
Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational within 14 days before enrollment
Known to be HIV positive

Show all 10Show fewer

Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV hear failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
Hypersensitivity to bortezomib, boron or mannitol
Serious medical or psychiatric illness likely to interfere with participation in this clinical trial
Patients who may need or are receiving live vaccines for immunization

Trial locations and contacts

3 sites in 1 country.

United States3 sites

University of Michigan
Ann Arbor, Michigan, 48109
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Washington University in Saint Louis
St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Phase I/II Trial of Combination CCI-779 (Temsirolimus) and Bortezomib (Velcade) in Relapsed and/or Relapsed/Refractory Multiple Myeloma

Read the detailed description

Since we are looking for the highest dose of CCI-779 (Temsirolimus) given in combination with bortezomib (Velcade) that can be given to people without causing the most serious or unmanageable side effects, not everyone who participates in this study will be receiving the same amount of either drug.
During the study treatment, participants will be given some medications to decrease the chance they they will have an allergic reaction to CCI-779 (Temsirolimus). After these drugs are given, participants will be receive bortezomib (Velcade) by injection followed by an injection of CCI-779 (Temsirolimus). These drugs wil be given once a week for four weeks (on Days 1, 8, 15, and 22). On the fifth week (Day 29), participants will be given only CCI-779 along with the drugs to decrease the chance of an allergic reaction.
The cycle will last 35 days and will occur twice before the doctor evaluates for response. The cycles will be repeated for up to 8 cycles as long as the participant does not have any severe or unmanageable side effects and the disease is responding to treatment.
While receiving study treatment, participants will be seen at the clinic at the start of each cycle for the following: complete physical examination, blood work, urine collection, x-ray of bones (if study doctor deems necessary) and an electrocardiogram (prior to treatment and at the end of treatment)
A bone skeletal survey will be performed at the end of treatment to measure the size of the participants tumors.
After 8 cycles of treatment or if the participant has ended treatment, more tests will be performed. A physical exam, blood work, urine collection, skeletal survey, electrocardiogram, bone marrow biopsy and aspirate will be performed.

Conditions: Multiple Myeloma
Being tested: CCI-779, Bortezomib
Keywords: Temsirolimus, Bortezomib
Medical subject headings: Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CCI-779Drug
Also called Temsirolimus
Given by injection once a week for 5 weeks (5 weeks equals one cycle) for up to 8 cycles
BortezomibDrug
Also called Velcade
Given by injection once a week for 4 weeks (a cycle equals 5 weeks) for up to 8 cycles

Study groups in NCT00483262
Study group	Role	What they receive
CCI779 and Bortezomib Phase I/II	Experimental	In Phase I part, 15 or 25 mg temsirolimus (CCI-779)and 1·3 or 1·6 mg/m² bortezomib was given once a week.In Phase II, patients received intravenous temsirolimus once a week on days 1, 8, 15, 22, and 29 for a cycle of 35 days, and intravenous bortezomib once a week on days 1, 8, 15, and 22 for a cycle of 35 days, the MTD ascertained in the Phase I part. Receives: Drug: CCI-779; Drug: Bortezomib

What is being measured

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

Toxicity. Number of Patients With Specific Toxicities Are Reported.
Toxicity of CCI-779 (Temsirolimus) and bortezomib (Velcade) in patients with multiple myeloma.
Measured: 10 months
Best Response to Combination Treatment
Response rate of PR or better to the combination treatment of CCI-779 (Temsirolimus) and bortezomib (Velcade) in patients with relapsed or refractory multiple myeloma
Measured: 10 months

Secondary outcomes (1)

Progression-Free Survival
Median time to progression or death
Measured: 10 months

Timeline

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

May 2007Feb 2012

First posted6 Jun 2007 (estimated)
Study startMay 2007
Primary completionJan 2011
Study completionFeb 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.
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 Dana-Farber Cancer 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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 63 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00483262
Sponsor's protocol ID: 06-365
Status last verified: Oct 2013
First submitted: 5 Jun 2007
Last updated: 11 Nov 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Ghobrial IM, Weller E, Vij R, Munshi NC, Banwait R, Bagshaw M, Schlossman R, Leduc R, Chuma S, Kunsman J, Laubach J, Jakubowiak AJ, Maiso P, Roccaro A, Armand P, Dollard A, Warren D, Harris B, Poon T, Sam A, Rodig S, Anderson KC, Richardson PG. Weekly bortezomib in combination with temsirolimus in relapsed or relapsed and refractory multiple myeloma: a multicentre, phase 1/2, open-label, dose-escalation study. Lancet Oncol. 2011 Mar;12(3):263-72. doi: 10.1016/S1470-2045(11)70028-6. Epub 2011 Feb 21.
PubMed 21345726

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?

See locations

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)
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Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
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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 11 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II Trial of Combination CCI-779 (Temsirolimus) and Bortezomib (Velcade) in Relapsed and/or Relapsed/Refractory Multiple Myeloma
ClinicalTrials.gov ID: NCT00483262
Acronym / sponsor ID: 06-365
Conditions: Multiple Myeloma
Keywords: Temsirolimus, Bortezomib
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 63 participants (actual)
Lead sponsor: Dana-Farber Cancer InstituteUniversity, hospital or other
Collaborators: Wyeth is now a wholly owned subsidiary of Pfizer, Millennium Pharmaceuticals, Inc.
Study start: May 2007
Primary completion: Jan 2011 (actual)
Study completion: Feb 2012 (actual)
First posted: 6 Jun 2007 (estimated)
Results: Posted 10 May 2013

Clinical summary

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

Detailed description

Since we are looking for the highest dose of CCI-779 (Temsirolimus) given in combination with bortezomib (Velcade) that can be given to people without causing the most serious or unmanageable side effects, not everyone who participates in this study will be receiving the same amount of either drug.
During the study treatment, participants will be given some medications to decrease the chance they they will have an allergic reaction to CCI-779 (Temsirolimus). After these drugs are given, participants will be receive bortezomib (Velcade) by injection followed by an injection of CCI-779 (Temsirolimus). These drugs wil be given once a week for four weeks (on Days 1, 8, 15, and 22). On the fifth week (Day 29), participants will be given only CCI-779 along with the drugs to decrease the chance of an allergic reaction.
The cycle will last 35 days and will occur twice before the doctor evaluates for response. The cycles will be repeated for up to 8 cycles as long as the participant does not have any severe or unmanageable side effects and the disease is responding to treatment.
While receiving study treatment, participants will be seen at the clinic at the start of each cycle for the following: complete physical examination, blood work, urine collection, x-ray of bones (if study doctor deems necessary) and an electrocardiogram (prior to treatment and at the end of treatment)
A bone skeletal survey will be performed at the end of treatment to measure the size of the participants tumors.
After 8 cycles of treatment or if the participant has ended treatment, more tests will be performed. A physical exam, blood work, urine collection, skeletal survey, electrocardiogram, bone marrow biopsy and aspirate will be performed.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
CCI779 and Bortezomib Phase I/II	Experimental	Drug: CCI-779, Drug: BortezomibIn Phase I part, 15 or 25 mg temsirolimus (CCI-779)and 1·3 or 1·6 mg/m² bortezomib was given once a week.In Phase II, patients received intravenous temsirolimus once a week on days 1, 8, 15, 22, and 29 for a cycle of 35 days, and intravenous bortezomib once a week on days 1, 8, 15, and 22 for a cycle of 35 days, the MTD ascertained in the Phase I part.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

18 years of age or older
Must have received prior therapy for their myeloma and have relapsed and/or relapsed/refractory multiple myeloma
Monoclonal protein in the serum of greater than or equal to 1 gm/dL or monoclonal light chain in the urine protein electrophoresis of greater than or equal to 200mg/24 hours, or measurable light chains by free light chain assay of greater than or equal to 10mg/dl, or measurable plasmacytoma
ECOG Performance Status 0, 1 or 2
Laboratory values as outlined in the protocol

Key exclusion criteria (10 listed)

Uncontrolled infection
Cytotoxic chemotherapy less than 2 weeks, or biologic therapy less than 2 weeks, or corticosteroids less than 2 weeks prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than myeloma.
Pregnant or nursing women
Men or women of childbearing potential who are unwilling to employ adequate contraception
Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational within 14 days before enrollment

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
CCI-779Also: TemsirolimusGiven by injection once a week for 5 weeks (5 weeks equals one cycle) for up to 8 cycles	Drug	CCI779 and Bortezomib Phase I/II
BortezomibAlso: VelcadeGiven by injection once a week for 4 weeks (a cycle equals 5 weeks) for up to 8 cycles	Drug	CCI779 and Bortezomib Phase I/II

Primary outcome

Toxicity. Number of Patients With Specific Toxicities Are Reported.
Time frame: 10 months
Toxicity of CCI-779 (Temsirolimus) and bortezomib (Velcade) in patients with multiple myeloma.
Best Response to Combination Treatment
Time frame: 10 months
Response rate of PR or better to the combination treatment of CCI-779 (Temsirolimus) and bortezomib (Velcade) in patients with relapsed or refractory multiple myeloma

1 secondary outcome

Progression-Free Survival
Time frame: 10 months

Results and safety

Results posted to the registry on 10 May 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CCI779 and Bortezomib Phase I	20	20
CCI779 and Bortezomib Phase II	43	43

Primary outcome: Toxicity. Number of Patients With Specific Toxicities Are Reported.

Time frame: 10 months. Number (95% Confidence Interval). Unit: percentage of patients

Measure	CCI779 Toxicity Phase I n = 20	CCI779 Toxicity Phase II n = 43
Value	90 (72 to 98)	79 (66 to 89)

CCI779 Toxicity Phase I: >= grade 3 adverse event proportion: .90 (90% CI .72 to .98)
CCI779 Toxicity Phase II: toxicity grade >=3 proportion: .79 (90% CI .66 to .89)

Population analysed: Any patient who was treated was included in the analysis.

Primary outcome: Best Response to Combination Treatment

Time frame: 10 months. Number (90% Confidence Interval). Unit: percentage of patients

Measure	CCI779 Response Phase I n = 20	CCI779 Response Phase II n = 43
Value	10 (2 to 28)	33 (21 to 47)

CCI779 Response Phase I: response rate of PR or better: 0.10 (90% CI .02 to .28)
CCI779 Response Phase II: response rate of PR or better: 0.33 (90% CI 0.21 to 0.47)

Population analysed: All patients included in analysis

1 secondary outcome is reported in the full results.

Adverse events

Time frame: June 2007 to December 2009. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Adverse Events CCI779 and Bortezomib Phase I	13 of 20 (65%)	18 of 20 (90%)	Not reported
Adverse Events CCI779 and Bortezomib Phase II	25 of 43 (58.1%)	34 of 43 (79.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21345726Ghobrial IM, Weller E, Vij R, Munshi NC, Banwait R, Bagshaw M, Schlossman R, Leduc R, Chuma S, Kunsman J, Laubach J, Jakubowiak AJ, Maiso P, Roccaro A, Armand P, Dollard A, Warren D, Harris B, Poon T, Sam A, Rodig S, Anderson KC, Richardson PG. Weekly bortezomib in combination with temsirolimus in relapsed or relapsed and refractory multiple myeloma: a multicentre, phase 1/2, open-label, dose-escalation study. Lancet Oncol. 2011 Mar;12(3):263-72. doi: 10.1016/S1470-2045(11)70028-6. Epub 2011 Feb 21.

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.

Irene Ghobrial, MD principal investigator

Dana-Farber Cancer Institute

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CCI-779 and Bortezomib in people with Multiple Myeloma, run by Dana-Farber Cancer Institute at 3 sites 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 5 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 11 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 10 May 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?

Toxicity. Number of Patients With Specific Toxicities Are Reported. (time frame: 10 months). 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 NCT00483262, 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 11 Nov 2013.