Multiple MyelomaPhase 2PANORAMA-5NCT02756663
Panobinostat in Combination With Carfilzomib and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma
A Phase 2 study testing panobinostat (capsules), carfilzomib (infusion) and dexamethasone (tablets) in people with Multiple Myeloma, run by Novartis Pharmaceuticals.
Trial summary
The purpose of this study is to investigate the anti-myeloma effect of panobinostat given at two different doses (10 mg and 20 mg oral) in combination with carfilzomib (20/56 mg/m2 i.v.) and low dose dexamethasone (20 mg oral) vs carfilzomib plus low-dose dexamethasone in patients with relapsed or relapsed and… 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 (capsules), carfilzomib (infusion) and dexamethasone (tablets)
- 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
- Dec 2016to Feb 2021
- Phase
- Phase 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
- Previous diagnosis of MM based on IMWG definitions (Rajkumar, 2014)
- Prior treatment with 1 to 3 prior lines of therapy
- Relapsed or relapsed and refractory MM
- Measureable disease at screening based on central laboratory assessment
- ECOG Performance status ≤ 2
- Acceptable lab values prior to starting study treatment
Who cannot join
- Primary refractory myeloma
- Prior treatment with DAC inhibitors including panobinostat
- Prior treatment with carfilzomib
- Allogeneic stem cell transplant recipient with graft versus host disease (either active or requiring immunosuppression)
- Any concomitant anti-cancer therapy besides the study treatment (bisphosphonates are permitted only if commenced prior to the start of screening period)
- Intolerance to dexamethasone or contraindication to carfilzomib or dexamethasone
- Unresolved diarrhea ≥ CTCAE grade 2 or a medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease)
- Other protocol-defined inclusion/exclusion criteria may apply.
About this study
Official title: A Randomized, Triple-arm, Controlled, Open-label, Multicenter Phase II Study Assessing Two Different Doses of Panobinostat in Combination With Carfilzomib and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma
The purpose of this study is to investigate the anti-myeloma effect of panobinostat given at two different doses (10 mg and 20 mg oral) in combination with carfilzomib (20/56 mg/m2 i.v.) and low dose dexamethasone (20 mg oral) vs carfilzomib plus low-dose dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. Safety and efficacy will be evaluated. Treatment will be administered in 4-week cycles until patients discontinue due to disease progression or unacceptable toxicity or for other reasons.
Patients who discontinue the study treatment for reasons other than documented disease progression will be followed for disease assessments every 8 weeks until progression. All patients will be followed for survival until 3 years have passed from their entry into the study, or they have discontinued the follow up earlier.
- Conditions
- Multiple Myeloma
- Being tested
- panobinostat (capsules), carfilzomib (infusion), dexamethasone (tablets)
- Keywords
- multiple myeloma, MM, relapsed, relapsed and refractory, panobinostat, LBH589, histone deacetylase inhibitor, carfilzomib, proteasome inhibitor
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
panobinostat (capsules)Drug
Also called PAN, LBH589
Panobinostat capsules, oral: 10mg, 15mg, 20mg dosing 3x a week, 1 week on / 1 week off, in a 4 week cycle (28 days). Treatment arm A: only capsules of 10mg will be used Treatment arm B: capsules of 10mg and 15mg are foreseen for dose reduction only.
carfilzomib (infusion)Drug
Also called CFZ
Carfilzomib infusion; 20 mg/m2 i.v. on C1D1 and C1D2; 56 mg/m2 i.v. on subsequent dosing days (2x a week; 3 weeks on/1 weeks off ); 4 week cycle (28 days)
dexamethasone (tablets)Drug
Also called Dex
Dexamethasone tablets p.o. 20 mg on days of carfilzomib infusion (2x week) and on D22 and D23 of each 4 week cycle (28 days)
| Study group | Role | What they receive |
|---|---|---|
| Arm A: PAN (10mg) + CFZ + Dex | Experimental | Panobinostat (PAN) 10mg orally, combined with carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle Receives: Drug: panobinostat (capsules); Drug: carfilzomib (infusion); Drug: dexamethasone (tablets) |
| Arm B: PAN (20mg) + CFZ + Dex | Experimental | Panobinostat (PAN) 20mg orally, combined with carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle Receives: Drug: panobinostat (capsules); Drug: carfilzomib (infusion); Drug: dexamethasone (tablets) |
| Arm C: CFZ + Dex | Active comparator | Carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle Receives: Drug: carfilzomib (infusion); Drug: dexamethasone (tablets) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR) using investigator's response assessment
The primary endpoint if Overall Response Rate (ORR) using investigator response assessment according to IMWG criteria. The analysis of ORR will be performed after all randomized patients have completed 6 months of study treatment or discontinued treatment earlier.
Measured: All patients treated for 6 cycles (cycle=28 days)
Secondary outcomes (11)
Very Good Partial Response (VGPR) or better as best response using investigator response assessment based on International Myeloma Working Group (IMWG) criteria
Investigators' response assessment assessed on IMWG criteria will be used. The VGPR or better rate is defined as the proportion of patients with a confirmed VGPR or better response as their best overall response.
Measured: All patients treated for 6 cycles (cycle=28 days)
Progression-free survival (PFS) using investigator's response assessment based on IMWG criteria
PFS is defined as the time from date of randomization to date of first documented disease progression or death (regardless of cause of death).
Measured: All patients treated for 6 cycles (cycle=28 days)
Overall survival (OS)
OS is defined as the time from date of randomization to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact.
Measured: All patients treated for 6 cycles (cycle=28 days)
Time to response (TTR) using investigator's response assessment based on IMWG criteria
TTR is the time between date of randomization to the date of first onset of partial response (PR) or better response.
Measured: All patients treated for 6 cycles (cycle=28 days)
Duration of Response (DOR) using investigator's response assessment based on IMWG criteria
DOR is defined as the duration from the first documented onset of PR or better response the date of first documented disease progression or death due to multiple myeloma. DOR will use only the patients with PR or better as their best response.
Measured: All patients treated for 6 cycles (cycle = 28 days)
Time to progression (TTP) using investigator's response assessment based on IMWG criteria
TTP is defined as the time from the date of randomization to the ate of the first documented disease progression or death due to multiple myeloma.
Measured: All patients treated for 6 cycles (cycle = 28 days)
Time to reach Cmax for panobinostat (PAN) and carfilzomib (CFZ)
The maximum (peak) observed plasma concentration after single and multiple dose administration (ng/mL) of PAN and CFZ.
Measured: All patients treated for 6 cycles (cycle=28 days);
Minimum observed plasma concentration (Cmin) for carfilzomib
The minimum (trough) observed plasma concentration after single and multiple dose administration (ng/mL) of PAN and CFZ.
Measured: All patients treated for 6 cycles (cycle=28 days)
Concentration of panobinostat in blood plasma in 48 hrs after the dose.
The area under the concentration-time curve (AUC) from time zero to 48 hours (ng*h/mL) after the dose of PAN
Measured: All patients treated for 6 cycles (cycle = 28 days)
Total carfilzomib exposure over time in blood plasma .
The AUC from time zero to infinity (ng*h/mL) for CFZ.
Measured: All patients treated for 6 cycles (cycle=28 days)
Health related quality of life (HRQoL) change over time measured by EORTC questionnaire QLQ-C30 and QLQ-MY20 for disease symptoms
HRQoL questionnaires are patient reported outcomes, which provide functional assessment of cancer therapy.
Measured: All patients treated for 6 cycles (cycle=28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2016 (estimated)
- Study startDec 2016
- Primary completionFeb 2021 (estimated)
- Study completionFeb 2021 (estimated)
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 Novartis PharmaceuticalsThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02756663
- Sponsor's protocol ID
- CLBH589X2201
- Acronym
- PANORAMA-5
- Status last verified
- Nov 2016
- First submitted
- 12 Apr 2016
- Last updated
- 8 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Triple-arm, Controlled, Open-label, Multicenter Phase II Study Assessing Two Different Doses of Panobinostat in Combination With Carfilzomib and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02756663
- Acronym / sponsor ID
- PANORAMA-5 / CLBH589X2201
- Conditions
- Multiple Myeloma
- Keywords
- multiple myeloma, MM, relapsed, relapsed and refractory, panobinostat, LBH589, histone deacetylase inhibitor, carfilzomib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Dec 2016
- Primary completion
- Feb 2021 (estimated)
- Study completion
- Feb 2021 (estimated)
- First posted
- 29 Apr 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 is to investigate the anti-myeloma effect of panobinostat given at two different doses (10 mg and 20 mg oral) in combination with carfilzomib (20/56 mg/m2 i.v.) and low dose dexamethasone (20 mg oral) vs carfilzomib plus low-dose dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. Safety and efficacy will be evaluated. Treatment will be administered in 4-week cycles until patients discontinue due to disease progression or unacceptable toxicity or for other reasons.
Patients who discontinue the study treatment for reasons other than documented disease progression will be followed for disease assessments every 8 weeks until progression. All patients will be followed for survival until 3 years have passed from their entry into the study, or they have discontinued the follow up earlier.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: PAN (10mg) + CFZ + Dex | Experimental | Drug: panobinostat (capsules), Drug: carfilzomib (infusion), Drug: dexamethasone (tablets)Panobinostat (PAN) 10mg orally, combined with carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle |
| Arm B: PAN (20mg) + CFZ + Dex | Experimental | Drug: panobinostat (capsules), Drug: carfilzomib (infusion), Drug: dexamethasone (tablets)Panobinostat (PAN) 20mg orally, combined with carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle |
| Arm C: CFZ + Dex | Active comparator | Drug: carfilzomib (infusion), Drug: dexamethasone (tablets)Carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Previous diagnosis of MM based on IMWG definitions (Rajkumar, 2014)
- Prior treatment with 1 to 3 prior lines of therapy
- Relapsed or relapsed and refractory MM
- Measureable disease at screening based on central laboratory assessment
- ECOG Performance status ≤ 2
Key exclusion criteria (8 listed)
- Primary refractory myeloma
- Prior treatment with DAC inhibitors including panobinostat
- Prior treatment with carfilzomib
- Allogeneic stem cell transplant recipient with graft versus host disease (either active or requiring immunosuppression)
- Any concomitant anti-cancer therapy besides the study treatment (bisphosphonates are permitted only if commenced prior to the start of screening period)
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 |
|---|---|---|
| panobinostat (capsules)Also: PAN, LBH589Panobinostat capsules, oral: 10mg, 15mg, 20mg dosing 3x a week, 1 week on / 1 week off, in a 4 week cycle (28 days). Treatment arm A: only capsules of 10mg will be used Treatment arm B: capsules of 10mg and 15mg are foreseen for dose reduction only. | Drug | Arm A: PAN (10mg) + CFZ + Dex, Arm B: PAN (20mg) + CFZ + Dex |
| carfilzomib (infusion)Also: CFZCarfilzomib infusion; 20 mg/m2 i.v. on C1D1 and C1D2; 56 mg/m2 i.v. on subsequent dosing days (2x a week; 3 weeks on/1 weeks off ); 4 week cycle (28 days) | Drug | Arm A: PAN (10mg) + CFZ + Dex, Arm B: PAN (20mg) + CFZ + Dex, Arm C: CFZ + Dex |
| dexamethasone (tablets)Also: DexDexamethasone tablets p.o. 20 mg on days of carfilzomib infusion (2x week) and on D22 and D23 of each 4 week cycle (28 days) | Drug | Arm A: PAN (10mg) + CFZ + Dex, Arm B: PAN (20mg) + CFZ + Dex, Arm C: CFZ + Dex |
Primary outcome
Overall response rate (ORR) using investigator's response assessment
Time frame: All patients treated for 6 cycles (cycle=28 days)
The primary endpoint if Overall Response Rate (ORR) using investigator response assessment according to IMWG criteria. The analysis of ORR will be performed after all randomized patients have completed 6 months of study treatment or discontinued treatment earlier.
11 secondary outcomes
Very Good Partial Response (VGPR) or better as best response using investigator response assessment based on International Myeloma Working Group (IMWG) criteria
Time frame: All patients treated for 6 cycles (cycle=28 days)
Progression-free survival (PFS) using investigator's response assessment based on IMWG criteria
Time frame: All patients treated for 6 cycles (cycle=28 days)
Overall survival (OS)
Time frame: All patients treated for 6 cycles (cycle=28 days)
Time to response (TTR) using investigator's response assessment based on IMWG criteria
Time frame: All patients treated for 6 cycles (cycle=28 days)
Duration of Response (DOR) using investigator's response assessment based on IMWG criteria
Time frame: All patients treated for 6 cycles (cycle = 28 days)
Time to progression (TTP) using investigator's response assessment based on IMWG criteria
Time frame: All patients treated for 6 cycles (cycle = 28 days)
Time to reach Cmax for panobinostat (PAN) and carfilzomib (CFZ)
Time frame: All patients treated for 6 cycles (cycle=28 days);
Minimum observed plasma concentration (Cmin) for carfilzomib
Time frame: All patients treated for 6 cycles (cycle=28 days)
Concentration of panobinostat in blood plasma in 48 hrs after the dose.
Time frame: All patients treated for 6 cycles (cycle = 28 days)
Total carfilzomib exposure over time in blood plasma .
Time frame: All patients treated for 6 cycles (cycle=28 days)
Health related quality of life (HRQoL) change over time measured by EORTC questionnaire QLQ-C30 and QLQ-MY20 for disease symptoms
Time frame: All patients treated for 6 cycles (cycle=28 days)
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 8 Nov 2016.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing panobinostat (capsules), carfilzomib (infusion) and dexamethasone (tablets) in people with Multiple Myeloma, run by Novartis Pharmaceuticals.
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 6 inclusion and 8 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 8 Nov 2016. 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 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?
Overall response rate (ORR) using investigator's response assessment (time frame: All patients treated for 6 cycles (cycle=28 days)). 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 8 Nov 2016.