Multiple MyelomaPhase 1NCT01680796
Dovitinib Combined With Bortezomib and Dexamethasone for Relapsed/Refractory Multiple Myeloma
A Phase 1 study testing Dovitinib, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by University of Florida.
Trial summary
This is an open-label phase I study in which dovitinib is given in combination with bortezomib and dexamethasone. Dovitinib dose escalation is planned in order to determine its maximum tolerated dose when given in this combination. 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?
- Dovitinib, Bortezomib and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Feb 2013to Feb 2013
- 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
- Diagnosis of multiple myeloma
- Karnofsky performance status ≥ 70
- Age ≥ 18 years old
- Evidence of relapsed or refractory disease as documented from the prior treatment history
- Have received at least 1, but not more than 3, prior treatment regimens for multiple myeloma including chemotherapy, autologous stem cell transplantation, immunotherapy, or other investigational agents. Prior allogeneic stem cell transplant and prior therapy with bortezomib (with no evidence of disease resistance to bortezomib) are permitted.
- Last dose of chemotherapy no less than 4 weeks prior to receipt of study medication and have recovered from the side effects of such therapy
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- Last dose of biological therapy, or antibody, or other investigational agents, no less than 4 weeks prior to receipt of study medication
- Subjects must have the following laboratory values:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin (Hgb) > 9 g/dL
- Serum total bilirubin: ≤ 1.5 x ULN
- ALT and AST ≤ 3.0 x ULN
- Serum creatinine ≤ 1.5 x ULN
- Willing and able to undergo bone marrow aspirates as per protocol, with/without bone marrow biopsy according to the study center's practice. - Life expectancy of ≥ 12 weeks
- All subjects (male and female) of child bearing potential must agree to use adequate contraceptive methods.
- Negative serum pregnancy test (≤ 72 hours prior to the first dosing of dovitinib) in all women of childbearing potential
- Subjects who give a written informed consent obtained according to local guidelines
Who cannot join
- Subjects with CNS (central nervous system) disease
- Subjects with another primary malignancy within 3 years prior to starting study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, or skin cancer
- Subjects who have received the last administration of an anticancer therapy including chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding nitrosurea, mitomycin-C, targeted therapy and radiation) ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
- Subjects who have had radiotherapy ≤ 4 weeks prior to starting study drug, or ≤ 2 weeks prior to starting study drug in the case of localized radiotherapy (e.g. for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities
- Subjects who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or subjects who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
- Subjects with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
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- Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- History or presence of serious uncontrolled ventricular arrhythmias
- Clinically significant resting bradycardia
- LVEF assessed by 2-D echocardiogram (ECHO) < 50% or lower limit of normal (whichever is higher) or multiple gated acquisition scan (MUGA) < 45% or lower limit of normal (whichever is higher).
- Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE)
- Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s),
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of dovitinib (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection),
- Cirrhosis, chronic active hepatitis or chronic persistent hepatitis,
- Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory),
- Subjects who are currently receiving anticoagulation treatment with therapeutic doses of warfarin,
- Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
- Pregnant or breast-feeding women
- Women of child-bearing potential, who are biologically able to conceive, not willing to employ two forms of highly effective contraception
- Fertile males not willing to use contraception
- Subject has a known hypersensitivity to bortezomib, or known Grade ≥ 2 bortezomib-related neuropathy
- Subjects unwilling or unable to comply with the protocol
About this study
Official title: Phase I, Open Label, Clinical Study to Determine the Maximum Tolerated Dose (MTD) of Oral Dovitinib (TKI258) When Given in Combination With Bortezomib and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma Patients
This is an open-label phase I study in which dovitinib is given in combination with bortezomib and dexamethasone. Dovitinib dose escalation is planned in order to determine its maximum tolerated dose when given in this combination.
- Conditions
- Multiple Myeloma
- Being tested
- Dovitinib, Bortezomib, Dexamethasone
- Keywords
- Multiple Myeloma, Relapsed Multiple Myeloma, Refractory 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.
DovitinibDrug
Also called TKI258
Dose Level 0: 200 mg daily
Dose Level 1: 300 mg daily
Dose Level 2: 300 mg daily
Dose Level 3: 400 mg daily
Dose Level 4: 500 mg daily
BortezomibDrug
Also called Velcade
Dose Level 0: 1.3 mg/m2 IV on days 1 and 8
Dose Level 1: 1.3 mg/m2 IV on days 1 and 8
Dose Level 2: 1.6 mg/m2 IV on days 1 and 8
Dose Level 3: 1.6 mg/m2 IV on days 1 and 8
Dose Level 4: 1.6 mg/m2 IV on days 1 and 8
DexamethasoneDrug
Also called Decadron
Dexamethasone 20 mg will be given orally on Days 1, 2, 8, and 9 of each 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Active Treatment | Experimental | Dovitinib will be given at up to four different dose levels beginning with dose level 1 on a 5 days on/2 days off dosing schedule of each 21-day cycle.
Bortezomib will be given at two different dose levels intravenously on Days 1 and 8 of each 21-day cycle.
Dexamethasone will be given orally on Days 1, 2, 8, and 9 of each 21-day cycle. Receives: Drug: Dovitinib; Drug: Bortezomib; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety and dose-limiting toxicity of treatment with dovitinib in combination with bortezomib/ dexamethasone.
Determination of the maximum tolerated dose of dovitinib will be based on Treatment Cycle 1 safety data for all subjects for whom all safety assessments during Treatment Cycle 1, as well as the pre-dosing safety assessments performed on Study Day 1 of Treatment Cycle 2, are completed and who do not receive alternate anti-neoplastic therapies during that period.
Measured: Treatment Cycle 1 (three weeks) for each participant.
Secondary outcomes (1)
To assess the overall response rate for the combination dovitinib/bortezomib/ dexamethasone in patients receiving at least 4 cycles of therapy.
Starting with Treatment Cycle 2, response to treatment will be determined during each treatment cycle (Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), and Stable Disease (SD)).
Measured: Participants will be followed for up to one year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2012 (estimated)
- Study startFeb 2013
- Primary completionFeb 2013
- Study completionFeb 2013
Why it stopped: The target drug, dovitinib, failed as a single agent in prior studies in patients with heavily treated multiple myeloma.
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 University of FloridaThe 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Jan S. Moreb, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01680796
- Sponsor's protocol ID
- CTKI258AU012T
- Status last verified
- Feb 2013
- First submitted
- 29 Aug 2012
- Last updated
- 20 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Open Label, Clinical Study to Determine the Maximum Tolerated Dose (MTD) of Oral Dovitinib (TKI258) When Given in Combination With Bortezomib and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma Patients
- ClinicalTrials.gov ID
- NCT01680796
- Acronym / sponsor ID
- CTKI258AU012T
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Relapsed Multiple Myeloma, Refractory Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The target drug, dovitinib, failed as a single agent in prior studies in patients with heavily treated multiple myeloma.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Feb 2013
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 7 Sep 2012 (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.
This is an open-label phase I study in which dovitinib is given in combination with bortezomib and dexamethasone. Dovitinib dose escalation is planned in order to determine its maximum tolerated dose when given in this combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Active Treatment | Experimental | Drug: Dovitinib, Drug: Bortezomib, Drug: DexamethasoneDovitinib will be given at up to four different dose levels beginning with dose level 1 on a 5 days on/2 days off dosing schedule of each 21-day cycle. Bortezomib will be given at two different dose levels intravenously on Days 1 and 8 of each 21-day cycle. Dexamethasone will be given orally on Days 1, 2, 8, and 9 of each 21-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Diagnosis of multiple myeloma
- Karnofsky performance status ≥ 70
- Age ≥ 18 years old
- Evidence of relapsed or refractory disease as documented from the prior treatment history
- Have received at least 1, but not more than 3, prior treatment regimens for multiple myeloma including chemotherapy, autologous stem cell transplantation, immunotherapy, or other investigational agents. Prior allogeneic stem cell transplant and prior therapy with bortezomib (with no evidence of disease resistance to bortezomib) are permitted.
Key exclusion criteria (22 listed)
- Subjects with CNS (central nervous system) disease
- Subjects with another primary malignancy within 3 years prior to starting study drug, with the exception of adequately treated in-situ carcinoma of the uterine cervix, or skin cancer
- Subjects who have received the last administration of an anticancer therapy including chemotherapy, immunotherapy, hormonal therapy and monoclonal antibodies (but excluding nitrosurea, mitomycin-C, targeted therapy and radiation) ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
- Subjects who have had radiotherapy ≤ 4 weeks prior to starting study drug, or ≤ 2 weeks prior to starting study drug in the case of localized radiotherapy (e.g. for analgesic purpose or for lytic lesions at risk of fracture), or who have not recovered from radiotherapy toxicities
- Subjects who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or subjects who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
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 |
|---|---|---|
| DovitinibAlso: TKI258Dose Level 0: 200 mg daily Dose Level 1: 300 mg daily Dose Level 2: 300 mg daily Dose Level 3: 400 mg daily Dose Level 4: 500 mg daily | Drug | Active Treatment |
| BortezomibAlso: VelcadeDose Level 0: 1.3 mg/m2 IV on days 1 and 8 Dose Level 1: 1.3 mg/m2 IV on days 1 and 8 Dose Level 2: 1.6 mg/m2 IV on days 1 and 8 Dose Level 3: 1.6 mg/m2 IV on days 1 and 8 Dose Level 4: 1.6 mg/m2 IV on days 1 and 8 | Drug | Active Treatment |
| DexamethasoneAlso: DecadronDexamethasone 20 mg will be given orally on Days 1, 2, 8, and 9 of each 21-day cycle. | Drug | Active Treatment |
Primary outcome
Evaluate the safety and dose-limiting toxicity of treatment with dovitinib in combination with bortezomib/ dexamethasone.
Time frame: Treatment Cycle 1 (three weeks) for each participant.
Determination of the maximum tolerated dose of dovitinib will be based on Treatment Cycle 1 safety data for all subjects for whom all safety assessments during Treatment Cycle 1, as well as the pre-dosing safety assessments performed on Study Day 1 of Treatment Cycle 2, are completed and who do not receive alternate anti-neoplastic therapies during that period.
1 secondary outcome
To assess the overall response rate for the combination dovitinib/bortezomib/ dexamethasone in patients receiving at least 4 cycles of therapy.
Time frame: Participants will be followed for up to one year.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2013.
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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.
Jan S. Moreb, MD principal investigator
University of Florida
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dovitinib, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by University of Florida.
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 18 inclusion and 22 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: withdrawn, as of the sponsor's last update on 20 Feb 2013. 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 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 was withdrawn before enrolling participants, so there are no results.
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?
Evaluate the safety and dose-limiting toxicity of treatment with dovitinib in combination with bortezomib/ dexamethasone. (time frame: Treatment Cycle 1 (three weeks) for each participant.). 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 20 Feb 2013.