Multiple MyelomaPhase 1/2NCT02802163
Induction Therapy for Multiple Myeloma With Carfilzomib, Lenalidomide,Dexamethasone,Panobinostat
A Phase 1/2 study testing Panobinostat, Carfilzomib and Lenalidomide in people with Multiple Myeloma, run by H. Lee Moffitt Cancer Center and Research Institute.
Trial summary
The purpose of this study for Phase l is to determine the maximum tolerated dose of panobinostat given in combination with carfilzomib, lenalidomide, and dexamethasone in 28-day cycles as induction (initial) therapy to participants with newly diagnosed 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?
- Panobinostat, Carfilzomib and Lenalidomide
- 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
- Jun 2017to Dec 2020
- Phase
- Phase 1/2
- 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
- Male or female patients aged ≥ 18 years old
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- Symptomatic multiple myeloma (per IMWG diagnostic criteria) and no prior treatment for multiple myeloma
- Measurable disease with at least 1 of the following assessed within 21 days prior to Cycle 1 Day 1: a.) Serum M-protein ≥ 0.5 g/d;, b.) Urine M-protein ≥ 200 mg/24 hour; c.) In potential participants without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio.
- Must meet the following laboratory criteria within 21 days prior to Cycle 1, day 1: a.) Absolute neutrophil count (ANC) ≥ 1 x 10^9/L; b.) Hemoglobin ≥ 8 g/dl; c.) Platelet count ≥ 75,000/mm^3 unless thrombocytopenia is due to marrow infiltration by myeloma; d.) AST and ALT ≤ 2.5 x upper limit of normal (ULN); e.) Serum bilirubin ≤ 1.5 x ULN; f.) Serum Creatinine clearance ≥ 50 ml/min.
- Baseline multiple uptake gated acquisition scan (MUGA) or echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥ 45%
- Females of childbearing potential (FCBP) must have a negative serum pregnancy test within the 10 to 14 days prior to study drug administration and a negative urine pregnancy test within the 24 hours prior to the first study drug administration and males who are sexually active with FCBP must agree to use 2 highly effective concomitant methods of contraception including a male condom during the study and for 90 days following the last dose of study treatment
Who cannot join
- Prior histone deacetylase (HDAC), deacetylase (DAC), HSP90 inhibitors or valproic acid for the treatment of cancer
- Potential participants who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
- Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible but should be discussed with principal investigator prior to enrollment); Any history of ventricular fibrillation or torsade de pointes; Bradycardia defined as HR< 50 bpm. (Patients with pacemakers are eligible if heart rate (HR) ≥ 50 bpm.); Screening ECG with a QTc > 450 msec; Right bundle branch block + left anterior hemiblock (bifascicular block); Patients with myocardial infarction or unstable angina ≤ 12 months prior to starting study drug; Other clinically significant heart disease (e.g., chronic heart failure (CHF) New York Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat
- Diarrhea > NCI common terminology criteria for adverse events (CTCAE) grade 2
- Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
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- Using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
- Have received prior treatment for multiple myeloma excluding dexamethasone not to exceed 160 mg total
- Have received radiation therapy to > 30% of marrow-bearing bone within < 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.
- Have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 24 hrs of receiving the first dose of study medication.
- Males whose sexual partners are WOCBP not using effective birth control
- A prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
- Known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline testing for HIV and hepatitis C is not required
- Any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff.
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
- Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
- Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
About this study
Official title: Phase I-II Study of Carfilzomib, Lenalidomide, Dexamethasone, and Panobinostat, Ca-R-Pa-Diem, as Induction Therapy for Newly Diagnosed, Untreated, Transplant-Eligible, Multiple Myeloma Patients
The purpose of this study for Phase l is to determine the maximum tolerated dose of panobinostat given in combination with carfilzomib, lenalidomide, and dexamethasone in 28-day cycles as induction (initial) therapy to participants with newly diagnosed multiple myeloma.
In Phase ll, investigators will evaluate the safety (side effects) and efficacy (effectiveness) of panobinostat in combination with carfilzomib, lenalidomide, and dexamethasone.
- Conditions
- Multiple Myeloma
- Being tested
- Panobinostat, Carfilzomib, Lenalidomide, Dexamethasone
- Keywords
- untreated multiple myeloma, newly diagnosed myeloma, transplant eligible
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanobinostatDrug
Also called LBH589, deacetylase inhibitor (DACi)
Induction Phase: Panobinostat (dose escalation beginning at 10 mg) will be administered 3 times a week (TIW) by mouth every other week starting on day 1 of each cycle.
Maintenance Phase: Panobinostat will be administered TIW by mouth every other week starting on day 1 of each cycle. The dose of panobinostat during maintenance phase will be the same dose taken during cyce 8 of induction phase.
CarfilzomibDrug
Also called Kyprolis
Induction Phase: Carfilzomib will be administered at 20 mg/m^2 on Cycle 1 Day 1. Beginning on Cycle 1 Day 2 the carfilzomib dose will be according to the assigned level of 27 mg/m^2 or 36 mg/m^2. Carfilzomib will be administered twice weekly IV on Days 1,2, 8,9,15, and 16.
LenalidomideDrug
Also called Revlimid
Induction Phase: Lenalidomide (25 mg) will be administered once-daily by mouth on Days 1-21, 25.
Maintenance Phase: Lenalidomide (10 mg) will be administered once-daily by mouth on days 1-21.
DexamethasoneDrug
Also called Decadron, corticosteroid
Induction Phase: Dexamethasone (20 mg) will be administered twice weekly by mouth or by IV on Days 1,2, 8, 9, 15, and 16.
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy | Experimental | Combination Therapy: Panobinostat, Carfilzomib, Lenalidomide, Dexamethasone (Ca-R-Pa-Diem) . Participants will receive up to 8 cycles of the combination as induction after which will proceed with consolidation therapy with transplant as per institutional standards. After transplant, participants receive maintenance with panobinostat/lenalidomide. The maintenance dose and schedule of panobinostat will be same given during induction for 1 year. The maintenance dose of lenalidomide will be 10 mg given for 21 days of 28 days cycle until disease progression. Receives: Drug: Panobinostat; Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Maximum Tolerated Dose (MTD)
MTD of the Ca-R-Pa-Diem given in combination to newly diagnosed Multiple Myeloma patients.
Measured: Up to 8 months
Secondary outcomes (2)
Stringent Complete Remission (sCR) Rate after 4 and 8 Cycles of Treatment
Response rates by International Myeloma Working Group Uniform Response Criteria (IMWG-URC). Complete Response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. sCR: CR plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
Measured: Up to 8 months
Phase II: Overall Response Rate (ORR)
Overall response rate will be the proportion of participants who achieved Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR). Response rate determined by IMWG-URC will be calculated based on the number of participants with each of response categories (sCR, CR, VGPR, PR, and progressive disease) at each treatment cycle.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2016 (estimated)
- Study startJun 2017 (estimated)
- Primary completionSep 2020 (estimated)
- Study completionDec 2020 (estimated)
Why it stopped: study drug unavailable
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 H. Lee Moffitt Cancer Center and Research 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
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, Amgen
- Responsible party
- Sponsor
- Investigators
- Melissa Alsina, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02802163
- Sponsor's protocol ID
- MCC-18665
- Status last verified
- Apr 2017
- First submitted
- 13 Jun 2016
- Last updated
- 25 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I-II Study of Carfilzomib, Lenalidomide, Dexamethasone, and Panobinostat, Ca-R-Pa-Diem, as Induction Therapy for Newly Diagnosed, Untreated, Transplant-Eligible, Multiple Myeloma Patients
- ClinicalTrials.gov ID
- NCT02802163
- Acronym / sponsor ID
- MCC-18665
- Conditions
- Multiple Myeloma
- Keywords
- untreated multiple myeloma, newly diagnosed myeloma, transplant eligible
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: study drug unavailable
- Enrolment
- 0 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Novartis, Amgen
- Study start
- Jun 2017 (estimated)
- Primary completion
- Sep 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 16 Jun 2016 (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 for Phase l is to determine the maximum tolerated dose of panobinostat given in combination with carfilzomib, lenalidomide, and dexamethasone in 28-day cycles as induction (initial) therapy to participants with newly diagnosed multiple myeloma.
In Phase ll, investigators will evaluate the safety (side effects) and efficacy (effectiveness) of panobinostat in combination with carfilzomib, lenalidomide, and dexamethasone.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination Therapy | Experimental | Drug: Panobinostat, Drug: Carfilzomib, Drug: Lenalidomide, Drug: DexamethasoneCombination Therapy: Panobinostat, Carfilzomib, Lenalidomide, Dexamethasone (Ca-R-Pa-Diem) . Participants will receive up to 8 cycles of the combination as induction after which will proceed with consolidation therapy with transplant as per institutional standards. After transplant, participants receive maintenance with panobinostat/lenalidomide. The maintenance dose and schedule of panobinostat will be same given during induction for 1 year. The maintenance dose of lenalidomide will be 10 mg given for 21 days of 28 days cycle until disease progression. |
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 patients aged ≥ 18 years old
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
- Symptomatic multiple myeloma (per IMWG diagnostic criteria) and no prior treatment for multiple myeloma
- Measurable disease with at least 1 of the following assessed within 21 days prior to Cycle 1 Day 1: a.) Serum M-protein ≥ 0.5 g/d;, b.) Urine M-protein ≥ 200 mg/24 hour; c.) In potential participants without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio.
- Must meet the following laboratory criteria within 21 days prior to Cycle 1, day 1: a.) Absolute neutrophil count (ANC) ≥ 1 x 10^9/L; b.) Hemoglobin ≥ 8 g/dl; c.) Platelet count ≥ 75,000/mm^3 unless thrombocytopenia is due to marrow infiltration by myeloma; d.) AST and ALT ≤ 2.5 x upper limit of normal (ULN); e.) Serum bilirubin ≤ 1.5 x ULN; f.) Serum Creatinine clearance ≥ 50 ml/min.
Key exclusion criteria (19 listed)
- Prior histone deacetylase (HDAC), deacetylase (DAC), HSP90 inhibitors or valproic acid for the treatment of cancer
- Potential participants who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
- Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible but should be discussed with principal investigator prior to enrollment); Any history of ventricular fibrillation or torsade de pointes; Bradycardia defined as HR< 50 bpm. (Patients with pacemakers are eligible if heart rate (HR) ≥ 50 bpm.); Screening ECG with a QTc > 450 msec; Right bundle branch block + left anterior hemiblock (bifascicular block); Patients with myocardial infarction or unstable angina ≤ 12 months prior to starting study drug; Other clinically significant heart disease (e.g., chronic heart failure (CHF) New York Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat
- Diarrhea > NCI common terminology criteria for adverse events (CTCAE) grade 2
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 |
|---|---|---|
| PanobinostatAlso: LBH589, deacetylase inhibitor (DACi)Induction Phase: Panobinostat (dose escalation beginning at 10 mg) will be administered 3 times a week (TIW) by mouth every other week starting on day 1 of each cycle. Maintenance Phase: Panobinostat will be administered TIW by mouth every other week starting on day 1 of each cycle. The dose of panobinostat during maintenance phase will be the same dose taken during cyce 8 of induction phase. | Drug | Combination Therapy |
| CarfilzomibAlso: KyprolisInduction Phase: Carfilzomib will be administered at 20 mg/m^2 on Cycle 1 Day 1. Beginning on Cycle 1 Day 2 the carfilzomib dose will be according to the assigned level of 27 mg/m^2 or 36 mg/m^2. Carfilzomib will be administered twice weekly IV on Days 1,2, 8,9,15, and 16. | Drug | Combination Therapy |
| LenalidomideAlso: RevlimidInduction Phase: Lenalidomide (25 mg) will be administered once-daily by mouth on Days 1-21, 25. Maintenance Phase: Lenalidomide (10 mg) will be administered once-daily by mouth on days 1-21. | Drug | Combination Therapy |
| DexamethasoneAlso: Decadron, corticosteroidInduction Phase: Dexamethasone (20 mg) will be administered twice weekly by mouth or by IV on Days 1,2, 8, 9, 15, and 16. | Drug | Combination Therapy |
Primary outcome
Phase I: Maximum Tolerated Dose (MTD)
Time frame: Up to 8 months
MTD of the Ca-R-Pa-Diem given in combination to newly diagnosed Multiple Myeloma patients.
2 secondary outcomes
Stringent Complete Remission (sCR) Rate after 4 and 8 Cycles of Treatment
Time frame: Up to 8 months
Phase II: Overall Response Rate (ORR)
Time frame: Up to 36 months
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 25 Apr 2017.
- Moffitt Cancer Center Clinical Trials websiteLink provided by the sponsor.
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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.
Melissa Alsina, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Panobinostat, Carfilzomib and Lenalidomide in people with Multiple Myeloma, run by H. Lee Moffitt Cancer Center and Research Institute.
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 19 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 25 Apr 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 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?
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?
Phase I: Maximum Tolerated Dose (MTD) (time frame: Up to 8 months). 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 25 Apr 2017.