Multiple MyelomaPhase 1NCT00608907
An Open-Label Study to Assess the Effect of CYP3A4 Induction on the Pharmacokinetics of VELCADE (Bortezomib)
A Phase 1 study testing bortezomib, bortezomib, rifampicin and bortezomib, dexamethasone in people with Multiple Myeloma and Non-Hodgkin's Lymphoma, run by Millennium Pharmaceuticals, Inc. at 9 sites in 5 countries.
Trial summary
The primary purpose of this Phase I study is to evaluate the effect of the co-administration of CYP3A4 inducers on the pharmacokinetics profile of VELCADE (bortezomib). Rifampicin will be used to assess the effect of a strong CYP3A4 inducer and dexamethasone to assess the effect of a relatively weak inducer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, Non-Hodgkin's Lymphoma
- What is being tested?
- bortezomib, bortezomib, rifampicin and bortezomib, dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 9 sitesin 5 countries
- Study dates
- Sep 2007to Apr 2010
- Phase
- Phase 1
- 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
- Male or female of at least 18 years of age.
- Has documented relapsed or refractory multiple myeloma or NHL following prior anti-neoplastic treatment.
- Female patients must be post menopausal for at least 1 year (must not have had a natural menses for at least 12 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; have a negative serum β-HCG or a negative urine pregnancy test at screening. (an alternative to oral contraceptives should be used if the patient is randomized to Arm B with rifampicin).
- Male patients must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study.
- Must be able to swallow capsules/tablets whole (without chewing, crushing, or opening).
- Agree to refrain from the use of any methylxanthine-containing products, including caffeine (e.g., chocolate bars or beverages, coffee, teas, or colas), on Day 11 of Cycles 2 and 3.
- Agree to refrain from the use of any products containing nicotine, alcohol, quinine, grapefruit juice, or Seville oranges from 7 days before the first administration of VELCADE through completion of the 72-hour PK blood sample collection (post Day 11 VELCADE dose) in Cycle 3.
Who cannot join
- Diagnosis or treatment of a malignancy other than multiple myeloma or NHL within 1 year of randomization, or who have previously been diagnosed with a malignancy other than multiple myeloma or NHL and have any radiographic or biochemical marker evidence of malignancy.
- History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, psychiatric, or metabolic disturbances.
- Known or suspected hypersensitivity or intolerance to rifampicin and/or other antibiotics, corticosteroids, boron or mannitol.
- Peripheral neuropathy or neuropathic pain Grade 2 or higher.
- Preplanned surgery or procedures that would interfere with the conduct of the study or major surgery within 2 weeks before randomization.
- History of disallowed therapies:
Show all 12Show fewer
- Prior treatment with VELCADE.
- Any drugs or agents that inhibit (e.g., cimetidine, erythromycin, fluoxetine, ketoconazole, paroxetine) or induce (e.g., carbamazepine, glucocorticoids, phenobarbital, phenytoin, St. John's Wort) CYP2C19 or CYP3A4 within 28 days before the first administration of VELCADE.
- Any exposure to rifampicin or corticosteroids within 28 days of screening.
- Have received an investigational agent or used an investigational medical device within 28 days before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study.
- Female patient who is pregnant or breastfeeding.
- Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
South Africa3 sites
Department of Hematology - University of the Free State
Bloemfontein, 9300
Hematological Oncology
Parow, Cape Town
Department of Medical Oncology - Ward 51 - Pretoria Academic Hospital
Pretoria, 0001
Poland2 sites
Medical Academy - Dept of Hematology and Transplantology
Gdansk, 80-952
Klinika Nowotworow Ukladu - Chlonnego - Centrum Onkologii - Instytut
Warsaw, 02-781
United Kingdom2 sites
Plymouth Hospitals NHS Trust - Derriford Hospital
Derriford, Plymouth, PL68DH
Hematology Department Combined Laboratories - Derriford Hospital
Plymouth, PL6 8DH
Israel1 site
Hematology Institute - Davidoff Center - Rabin Medical Center
Petah Tikva, 49100
Italy1 site
Divisione di Ematologia - Ospedale S Eugenio - P. le dell'Umanesimo
Rome, 10001
About this study
The primary purpose of this Phase I study is to evaluate the effect of the co-administration of CYP3A4 inducers on the pharmacokinetics profile of VELCADE (bortezomib). Rifampicin will be used to assess the effect of a strong CYP3A4 inducer and dexamethasone to assess the effect of a relatively weak inducer. This study is also to evaluate the impact of CYP3A4 inducers on the pharmacodynamics (PD) of VELCADE and the safety profile of VELCADE.
- Conditions
- Multiple Myeloma, Non-Hodgkin's Lymphoma
- Being tested
- bortezomib, bortezomib, rifampicin, bortezomib, dexamethasone
- Medical subject headings
- Multiple Myeloma, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
Also called VELCADE
1.3 mg/m^3 on days 1, 4, 8, 11 over a 21-day treatment cycle
bortezomib, rifampicinDrug
Also called bortezomib, rifampicin
bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg once daily days 4 to 10 in cycle 3
bortezomib, dexamethasoneDrug
Also called bortezomib, dexamethasone
bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg once daily days 1 to 4, and 9 to 12 in cycle 3
| Study group | Role | What they receive |
|---|---|---|
| VELCADE | Experimental | Control arm, bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle. Receives: Drug: bortezomib |
| VELCADE + rifampicin | Experimental | Treatment Arm, bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg once daily days 4 to 10 in cycle 3. Receives: Drug: bortezomib, rifampicin |
| VELCADE + dexamethasone | Experimental | Treatment arm, bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg once daily days 1 to 4, and 9 to 12 in cycle 3. Receives: Drug: bortezomib, dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Plasma Concentration-time Curve (AUC) 0-72 Hours
Measured: Cycle 3 day 14 (72 hours post last dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2008 (estimated)
- Study startSep 2007
- Primary completionMar 2010
- 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.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00608907
- Sponsor's protocol ID
- 26866138-CAN-1006
- Status last verified
- Jan 2012
- First submitted
- 23 Jan 2008
- Last updated
- 30 Jan 2012
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Assess the Effect of CYP3A4 Induction on the Pharmacokinetics of VELCADE (Bortezomib)
- ClinicalTrials.gov ID
- NCT00608907
- Acronym / sponsor ID
- 26866138-CAN-1006
- Conditions
- Multiple Myeloma, Non-Hodgkin's Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
- Study start
- Sep 2007
- Primary completion
- Mar 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 6 Feb 2008 (estimated)
- Results
- Posted 13 Jul 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this Phase I study is to evaluate the effect of the co-administration of CYP3A4 inducers on the pharmacokinetics profile of VELCADE (bortezomib). Rifampicin will be used to assess the effect of a strong CYP3A4 inducer and dexamethasone to assess the effect of a relatively weak inducer. This study is also to evaluate the impact of CYP3A4 inducers on the pharmacodynamics (PD) of VELCADE and the safety profile of VELCADE.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| VELCADE | Experimental | Drug: bortezomibControl arm, bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle. |
| VELCADE + rifampicin | Experimental | Drug: bortezomib, rifampicinTreatment Arm, bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg once daily days 4 to 10 in cycle 3. |
| VELCADE + dexamethasone | Experimental | Drug: bortezomib, dexamethasoneTreatment arm, bortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg once daily days 1 to 4, and 9 to 12 in cycle 3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female of at least 18 years of age.
- Has documented relapsed or refractory multiple myeloma or NHL following prior anti-neoplastic treatment.
- Female patients must be post menopausal for at least 1 year (must not have had a natural menses for at least 12 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; have a negative serum β-HCG or a negative urine pregnancy test at screening. (an alternative to oral contraceptives should be used if the patient is randomized to Arm B with rifampicin).
- Male patients must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study.
- Must be able to swallow capsules/tablets whole (without chewing, crushing, or opening).
Key exclusion criteria (12 listed)
- Diagnosis or treatment of a malignancy other than multiple myeloma or NHL within 1 year of randomization, or who have previously been diagnosed with a malignancy other than multiple myeloma or NHL and have any radiographic or biochemical marker evidence of malignancy.
- History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, psychiatric, or metabolic disturbances.
- Known or suspected hypersensitivity or intolerance to rifampicin and/or other antibiotics, corticosteroids, boron or mannitol.
- Peripheral neuropathy or neuropathic pain Grade 2 or higher.
- Preplanned surgery or procedures that would interfere with the conduct of the study or major surgery within 2 weeks before randomization.
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 |
|---|---|---|
| bortezomibAlso: VELCADE1.3 mg/m^3 on days 1, 4, 8, 11 over a 21-day treatment cycle | Drug | VELCADE |
| bortezomib, rifampicinAlso: bortezomib, rifampicinbortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, rifampicin 600 mg once daily days 4 to 10 in cycle 3 | Drug | VELCADE + rifampicin |
| bortezomib, dexamethasoneAlso: bortezomib, dexamethasonebortezomib 1.3 mg/m^2 on days 1, 4, 8, 11 over a 21-day treatment cycle, dexamethasone 40 mg once daily days 1 to 4, and 9 to 12 in cycle 3 | Drug | VELCADE + dexamethasone |
Primary outcome
Area Under the Plasma Concentration-time Curve (AUC) 0-72 Hours
Time frame: Cycle 3 day 14 (72 hours post last dose)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Medical Monitor study director
Millennium Pharmaceuticals, Inc.
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bortezomib, bortezomib, rifampicin and bortezomib, dexamethasone in people with Multiple Myeloma and Non-Hodgkin's Lymphoma, run by Millennium Pharmaceuticals, Inc. at 9 sites in 5 countries.
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 7 inclusion and 12 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 30 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in South Africa, Poland, United Kingdom, Israel, Italy. 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 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.
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 13 Jul 2011). 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?
Area Under the Plasma Concentration-time Curve (AUC) 0-72 Hours (time frame: Cycle 3 day 14 (72 hours post last dose)). 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 30 Jan 2012; AzTrials last refreshed its copy on 6 Nov 2026.