Multiple MyelomaPhase 1NCT00972712
Protocol of the Combination of Bortezomib and Tipifarnib for Relapsed or Refractory Multiple Myeloma
A Phase 1 study testing Bortezomib and Tipifarnib in people with Multiple Myeloma, run by Emory University at 3 sites in 2 countries.
Trial summary
The purpose of this study is to test the effect of the combination of bortezomib and tipifarnib. Bortezomib (VELCADE) is approved by the Food and Drug Administration (FDA) for the treatment of multiple myeloma patients who have received at least one prior therapy. 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?
- Bortezomib and Tipifarnib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Dec 2006to Mar 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Patients included in the study must meet criteria for relapsed or refractory multiple myeloma. Relapsed myeloma is defined in patients as increasing M-Spike or plasmacytoma compared to a previous measurement confirmed on at least two different settings. Refractory myeloma is defined as progression of disease on current therapy, and having received at least two courses of treatment with or without the use of high dose therapy and autologous transplant.
- Patients must have received at least 2 prior lines of therapy in order to be eligible for this treatment.
- Must be ≥ 18 years of age. Because no dosing or adverse event data are currently available on the use of bortezomib in combination with tipifarnib in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric phase 1 combination trials.
- Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2 (Karnofsky ≥ 60%, see Appendix A).
- Life expectancy of greater than 12 weeks.
- Patients must have organ and marrow function as defined below:
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- Leukocytes ≥ 1,000/microliter (mcL)
- Absolute neutrophil count ≥ 500/mcL
- Platelets ≥ 25,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 X institutional upper limit of normal
- Creatinine ≤ 2.5 OR
- Creatinine clearance ≥ 20 mL/min/1.73 m² for patients with creatinine levels above institutional normal.
- Eligibility of patients receiving any medications or substances with the potential or known to affect the activity or pharmacokinetics of bortezomib or tipifarnib will be determined following review of their case by the Principal Investigator. Patients must be on bisphosphonates therapy unless precluded by osteonecrosis of the jaw (ONJ) or other clinical circumstances at the investigators discretion. Patients may receive erythroid growth factors as needed, per institutional guidelines. Patients cannot be receiving enzyme-inducing antiepileptic drugs (EIAEDs) (e.g., phenytoin, carbamazepine, phenobarbital) nor any other cytochrome P450 3A4 (CYP3A4) inducer such as rifampin or St. John's wort.
- The effects of bortezomib and tipifarnib on the developing human fetus are unknown. For this reason, women with child-bearing potential and men must agree to use adequate contraception prior to entering the study. Adequate contraception includes hormonal therapy, a barrier method of birth control or abstinence. Appropriate contraception must be used for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately, and will be immediately discontinued from the study. Any woman who becomes pregnant during the study will be followed throughout their pregnancy until its outcome (i.e. delivery, still birth, miscarriage).
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- Male subject agrees to use an acceptable method of contraception for the duration of the study.
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Both men and women of all races and ethnic groups are eligible for this trial.
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to boronic acid, bortezomib, tipifarnib, or other agents used in study. Known allergy to imidazole drugs, such as clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, tioconazole or terconazole.
- Patients with a poorly controlled intercurrent illness will be excluded including but not limited to those with ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social climate that would limit compliance with study requirements.
- Pregnant women are excluded from this study because bortezomib and tipifarnib are Class D agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bortezomib and tipifarnib, breastfeeding should be discontinued if the mother is treated with bortezomib and tipifarnib. These potential risks may also apply to other agents used in this study.
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- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with bortezomib and tipifarnib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
- Other Exclusion Criteria
- Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment.
- Patient has hypersensitivity to boron or mannitol.
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum ß-human chorionic gonadotropin (ß-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs with 14 days before enrollment.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical trial.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
City of Hope Cancer Institute
Duarte, California, 91010
About this study
Official title: A Phase I Protocol of the Combination Bortezomib and Tipifarnib for Relapsed or Refractory Multiple Myeloma
The purpose of this study is to test the effect of the combination of bortezomib and tipifarnib. Bortezomib (VELCADE) is approved by the Food and Drug Administration (FDA) for the treatment of multiple myeloma patients who have received at least one prior therapy. Tipifarnib is not yet approved by the FDA and is an investigational drug. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it. Because these drugs have not been used together before, it is not clear which dose of each agent is optimal when used in combination.
This research study is a Phase I clinical trial. Phase I clinical trials test the safety of an investigational drug. Phase I studies also try to define the appropriate dose of the investigational drugs to use for further studies. The investigators will test the safety of BORTEZOMIB and TIPIFARNIB together and see what effects (good and bad) it has on you and your MULTIPLE MYELOMA, and to find the highest dose of both agents that can be given without causing severe side effects.
- Conditions
- Multiple Myeloma
- Being tested
- Bortezomib and Tipifarnib
- Keywords
- Multiple Myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bortezomib and TipifarnibDrug
Also called Velcade, Zarnestra
Dose level -1: Bortezomib (0.7 mg/m²; days 1,4,8,11); Tipifarnib (100 mg po BID)
Dose level 1: Bortezomib (1.0 mg/m²; days 1,4,8,11); Tipifarnib (100 mg po BID)
Dose level 2: Bortezomib (1.0 mg/m²; days 1,4,8,11); Tipifarnib (200 mg po BID)
Dose level 3: Bortezomib (1.0 mg/m²; days 1,4,8,11); Tipifarnib (300 mg po BID)
Dose level 4: Bortezomib (1.0 mg/m²; days 1,4,8,11); Tipifarnib (400 mg po BID)
Schema B
Dose level 1: Bortezomib (1.3 mg/m²; Days 1,4,8,11); Tipifarnib (300 mg po BID)
Dose level 2: Bortezomib (1.3 mg/m²; Days 1,4,8,11); Tipifarnib (400 mg po BID)
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Bortezomib and Tipifarnib Receives: Drug: Bortezomib and Tipifarnib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events based on the NCI Common Terminology Criteria (CTC) version 3.0
Measured: Ongoing from start of treatment until 30 days post
Secondary outcomes (1)
Laboratory tests to include: serum protein electrophoresis, quantitative immunoglobulins assay and immunofixation, 24 hour urine collection for Bence Jones protein, total proteins, and creatinine, bone marrow aspiration and analysis for plasma cells
Measured: Every 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2009 (estimated)
- Study startDec 2006
- Primary completionDec 2009
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Emory 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc., Ortho Biotech, Inc.
- Responsible party
- Principal investigator, Sagar Lonial, Emory University
- Investigators
- Sagar Lonial, MD, Principal investigator, Emory University Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00972712
- Sponsor's protocol ID
- IRB00000655
- Other IDs
- WCI1192-06
- Status last verified
- Mar 2015
- First submitted
- 3 Sep 2009
- Last updated
- 10 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Protocol of the Combination Bortezomib and Tipifarnib for Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00972712
- Acronym / sponsor ID
- IRB00000655
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc., Ortho Biotech, Inc.
- Study start
- Dec 2006
- Primary completion
- Dec 2009 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 7 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the effect of the combination of bortezomib and tipifarnib. Bortezomib (VELCADE) is approved by the Food and Drug Administration (FDA) for the treatment of multiple myeloma patients who have received at least one prior therapy. Tipifarnib is not yet approved by the FDA and is an investigational drug. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it. Because these drugs have not been used together before, it is not clear which dose of each agent is optimal when used in combination.
This research study is a Phase I clinical trial. Phase I clinical trials test the safety of an investigational drug. Phase I studies also try to define the appropriate dose of the investigational drugs to use for further studies. The investigators will test the safety of BORTEZOMIB and TIPIFARNIB together and see what effects (good and bad) it has on you and your MULTIPLE MYELOMA, and to find the highest dose of both agents that can be given without causing severe side effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Bortezomib and TipifarnibBortezomib and Tipifarnib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients included in the study must meet criteria for relapsed or refractory multiple myeloma. Relapsed myeloma is defined in patients as increasing M-Spike or plasmacytoma compared to a previous measurement confirmed on at least two different settings. Refractory myeloma is defined as progression of disease on current therapy, and having received at least two courses of treatment with or without the use of high dose therapy and autologous transplant.
- Patients must have received at least 2 prior lines of therapy in order to be eligible for this treatment.
- Must be ≥ 18 years of age. Because no dosing or adverse event data are currently available on the use of bortezomib in combination with tipifarnib in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric phase 1 combination trials.
- Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2 (Karnofsky ≥ 60%, see Appendix A).
- Life expectancy of greater than 12 weeks.
Key exclusion criteria (14 listed)
- Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to boronic acid, bortezomib, tipifarnib, or other agents used in study. Known allergy to imidazole drugs, such as clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, tioconazole or terconazole.
- Patients with a poorly controlled intercurrent illness will be excluded including but not limited to those with ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social climate that would limit compliance with study requirements.
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 |
|---|---|---|
| Bortezomib and TipifarnibAlso: Velcade, ZarnestraDose level -1: Bortezomib (0.7 mg/m²; days 1,4,8,11); Tipifarnib (100 mg po BID) Dose level 1: Bortezomib (1.0 mg/m²; days 1,4,8,11); Tipifarnib (100 mg po BID) Dose level 2: Bortezomib (1.0 mg/m²; days 1,4,8,11); Tipifarnib (200 mg po BID) Dose level 3: Bortezomib (1.0 mg/m²; days 1,4,8,11); Tipifarnib (300 mg po BID) Dose level 4: Bortezomib (1.0 mg/m²; days 1,4,8,11); Tipifarnib (400 mg po BID) Schema B Dose level 1: Bortezomib (1.3 mg/m²; Days 1,4,8,11); Tipifarnib (300 mg po BID) Dose level 2: Bortezomib (1.3 mg/m²; Days 1,4,8,11); Tipifarnib (400 mg po BID) | Drug | A |
Primary outcome
Adverse events based on the NCI Common Terminology Criteria (CTC) version 3.0
Time frame: Ongoing from start of treatment until 30 days post
1 secondary outcome
Laboratory tests to include: serum protein electrophoresis, quantitative immunoglobulins assay and immunofixation, 24 hour urine collection for Bence Jones protein, total proteins, and creatinine, bone marrow aspiration and analysis for plasma cells
Time frame: Every 21 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2015.
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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.
Sagar Lonial, MD principal investigator
Emory University Winship Cancer Institute
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bortezomib and Tipifarnib in people with Multiple Myeloma, run by Emory University at 3 sites in 2 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 19 inclusion and 14 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 10 Mar 2015. 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, Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Adverse events based on the NCI Common Terminology Criteria (CTC) version 3.0 (time frame: Ongoing from start of treatment until 30 days post). 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 10 Mar 2015.