Multiple MyelomaPhase 2PANORAMA4NCT02720510
A Trial Evaluating Efficacy & Safety of RVD +/- Panobinostat in Transplant Eligible, Newly Diagnosed Multiple Myeloma (NDMM)
A Phase 2 study testing Revlimid, Velcade and dexamethasone in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 5 sites in United States.
Trial summary
This was a multicenter, open-label, randomized phase II study which were to enroll 112 newly diagnosed symptomatic multiple myeloma patients in a 1:1 fashion. Patients were to enroll at approximately 20 centers in the United States. Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Revlimid, Velcade and dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 5 sitesUnited States
- Study dates
- 14 Jun 2016to 22 May 2017
- Phase
- Phase 2
- 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 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient newly diagnosed with multiple myeloma, based on following IMWG 2014 definition (Rajkumar et al 2014):
- Clonal bone marrow plasma cells ≥ 10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events:
- Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder
- Any one or more of the following biomarkers of malignancy:
- Clonal bone marrow plasma cell percentage ≥ 60%
- Involved: uninvolved serum free light chain ratio ≥ 100
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- >1 focal lesions on MRI studies
- Patient with measurable disease defined by at least 1 of the following conditions present at screening:
- Serum M-protein by Protein Electrophoresis (PEP) ≥ 1.0 g/dL (≥ 10 g/L).
- Urine M-protein by PEP ≥ 200 mg/24 hours. Involved serum free light chain level ≥ 10 mg/dL (≥ 100 mg/L), provided that the serum free light chain ratio is abnormal.
- Patient eligible for autologous stem cell transplantation based on the investigator's clinical judgment.
- Patient with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
- Patient's age ≥ 18 and <75 years at time of signing the informed consent
- Patient provided written informed consent prior to any screening procedures
- Women of childbearing potential (WOCBP) with a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline
Who cannot join
- Patients eligible for this study must not meet any of the following criteria:
- Any concomitant anti-cancer therapy (other than bortezomib/lenalidomide/dexamethasone; bisphosphonates are permitted only if commenced prior to the start of screening period)
- Unresolved diarrhea ≥ CTCAE grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease).
- Allogeneic stem cell transplant recipient presenting with graft versus host disease either active or requiring immunosuppression
- Patient shown intolerance to bortezomib or to dexamethasone or components of these drugs or has any contraindication to one or the other drug, following locally applicable prescribing information
- Patient with rade ≥ 2 peripheral neuropathy or grade 1 peripheral neuropathy with pain on clinical examination at screening
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- Patient received prior treatment with DAC inhibitors including Panobinostat
- Patient needing valproic acid for any medical condition during the study or within 5 days prior to first administration of panobinostat/study treatment.
- Patient taking any anti-cancer therapy concomitantly (bisphosphonates are permitted only if commenced prior to the start of screening period)
- Patient who received:
- prior anti-myeloma chemotherapy or medication including Immunomodulator (IMiDs) and Dex ≤ 3 weeks prior to start of study.
- experimental therapy or biologic immunotherapy including monoclonal antibodies ≤ 4 weeks prior to start of study.
- prior radiation therapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior start of study.
- Patient has not recovered from all therapy-related toxicities associated with above listed treatments to < grade 2 CTCAE.
- Patient undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy to < grade 2 CTCAE
- Patients with evidence of mucosal or internal bleeding
- Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 month prior to screening)
- Inability to determine the Fridericia's Correction Formula (QTc) F interval
- Patient with an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat (e.g. ulcerative disease, uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or small bowel resection)
- Sexually active males unless they use a condom during intercourse while taking the drug during treatment, and for 6 months after stopping treatment
- Pregnant or nursing (lactating) women.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Northside Hospital Central Research Dept.
Atlanta, Georgia, 30342
David Geffen School of Medicine at UCLA UCLA
Los Angeles, California, 90095
Oncology Hematology West Nebraska Cancer Specialists dbaNebraska Cancer Specialists
Omaha, Nebraska, 68124
Memorial West Cancer Center Memorial Cancer Institute
Pembroke Pines, Florida, 33028
Brooke Army Medical Center Hematology/Oncology
San Antonio, Texas, 78234
About this study
Official title: A Randomized, Phase II Trial Evaluating the Efficacy and Safety of Lenalidomide, Bortezomib and Dexamethasone (RVD) With or Without Panobinostat in Transplant Eligible, Newly Diagnosed Multiple Myeloma
This was a multicenter, open-label, randomized phase II study which were to enroll 112 newly diagnosed symptomatic multiple myeloma patients in a 1:1 fashion. Patients were to enroll at approximately 20 centers in the United States.
Patients were to undergo stem cell mobilization with plerixafor plus Granulocyte Colony Stimulating Factor (G-CSF), according to investigator discretion, after 4 cycles of induction therapy. Study treatment interruption for stem cell collection were not to exceed 30 days. All patients were to receive one additional cycle of study treatment after stem cell collection and then proceed to autologous transplant using melphalan 200mg/m2(140mg/m2 for patients > 70 years), as conditioning.
Read more
After Autologus Stem Cell Transplant( ASCT), patients still on study were to initiate maintenance therapy within the 60-120 day period following ASCT, provided they have adequate blood count and clinical recovery. Patients in the RVD arm were to initiate maintenance therapy with lenalidomide alone, and patients in RVD-panobinostat arm were to receive lenalidomide + panobinostat maintenance. Lenalidomide were to be dosed orally at 10mg/day continuously in both arms, increasing to 15mg/day after the first 84 day cycle. Panobinostat were to be dosed at 10mg three times a week, every other week. Total planned duration of maintenance therapy were to be 3 years.
Patients were to remain on study treatment until they complete the maintenance phase, or until they experience disease progression, unacceptable toxicity, or at the discretion of the Investigator.
- Conditions
- Multiple Myeloma
- Being tested
- Revlimid, Velcade, dexamethasone, Farydak
- Keywords
- multiple myeloma, farydak, panobinostat, LBH589, ASCT, transplant
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RevlimidDrug
Also called lenalidomide
Revlimid was used with dexamethasone to treat patients with multiple myeloma
VelcadeDrug
Also called bortezomib
Velcade was a proteasome inhibitor indicated for treatment of patients with multiple myeloma
dexamethasoneDrug
Also called Decadron
Dexamethasone was a steroid used to treat patients with multiple myeloma.
FarydakDrug
Also called panobinostat, LBH589
FARYDAK® (panobinostat) capsules was a prescription medicine used, in combination with bortezomib and dexamethasone, to treat adults with a type of cancer called multiple myeloma after at least 2 other types of treatment have been tried.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 - RVD + Pan | Active comparator | Revlimid, Velcade, dexamethasone and Farydak Receives: Drug: Revlimid; Drug: Velcade; Drug: dexamethasone; Drug: Farydak |
| Arm 2 - RVD | Active comparator | Revlimid, Velcade and Dexamethasone Receives: Drug: Revlimid; Drug: Velcade; Drug: dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Near Complete Response (nCR)/CR Rate of the Combination of Panobinostat With Bortezomib, Lenalidomide and Dexamethasone (P-RVD) vs RVD in Newly Diagnosed Multiple Myeloma Patients
Measured: 84 days
Secondary outcomes (6)
Minimal Residual Disease (MRD) Negativity (mCR) After 4 Cycles of Induction by Next Gen Sequencing
MRD negativity by Clonal Sequencing (ClonoSEQTM) assay (Adaptive Biotechnologies)
Measured: Month 3
Best Overall Response Rate (ORR) and MRD Negativity After ASCT and Maintenance
ORR (CR + PR) and MRD negativity after ASCT and maintenance
Measured: Month 3 up to end of study, approximately 3 years.
Depth of Response by International Myeloma Working Group (IMWG) Criteria
Rate of Very Good Partial Response (VGPR), Complete Response (CR) and Stringent Complete Response (sCR)
Measured: Day 22 up to end of study, approximately 3 years
Duration of Response
Measured: From measurable response to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.
Overall Survival
Measured: 3 years after the last patient is enrolled to the study
Progression Free Survival
Measured: 3 years after the last patient is enrolled to the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2016 (estimated)
- Study start14 Jun 2016
- Primary completion22 May 2017
- Study completion22 May 2017
Why it stopped: A study was terminated due to low enrollment.
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.
- 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
- 6 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
- NCT02720510
- Sponsor's protocol ID
- CLBH589DUS106
- Acronym
- PANORAMA4
- Status last verified
- Jun 2018
- First submitted
- 9 Mar 2016
- Last updated
- 24 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Phase II Trial Evaluating the Efficacy and Safety of Lenalidomide, Bortezomib and Dexamethasone (RVD) With or Without Panobinostat in Transplant Eligible, Newly Diagnosed Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02720510
- Acronym / sponsor ID
- PANORAMA4 / CLBH589DUS106
- Conditions
- Multiple Myeloma
- Keywords
- multiple myeloma, farydak, panobinostat, LBH589, ASCT, transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: A study was terminated due to low enrollment.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 14 Jun 2016 (actual)
- Primary completion
- 22 May 2017 (actual)
- Study completion
- 22 May 2017 (actual)
- First posted
- 28 Mar 2016 (estimated)
- Results
- Posted 24 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a multicenter, open-label, randomized phase II study which were to enroll 112 newly diagnosed symptomatic multiple myeloma patients in a 1:1 fashion. Patients were to enroll at approximately 20 centers in the United States.
Patients were to undergo stem cell mobilization with plerixafor plus Granulocyte Colony Stimulating Factor (G-CSF), according to investigator discretion, after 4 cycles of induction therapy. Study treatment interruption for stem cell collection were not to exceed 30 days. All patients were to receive one additional cycle of study treatment after stem cell collection and then proceed to autologous transplant using melphalan 200mg/m2(140mg/m2 for patients > 70 years), as conditioning.
After Autologus Stem Cell Transplant( ASCT), patients still on study were to initiate maintenance therapy within the 60-120 day period following ASCT, provided they have adequate blood count and clinical recovery. Patients in the RVD arm were to initiate maintenance therapy with lenalidomide alone, and patients in RVD-panobinostat arm were to receive lenalidomide + panobinostat maintenance. Lenalidomide were to be dosed orally at 10mg/day continuously in both arms, increasing to 15mg/day after the first 84 day cycle. Panobinostat were to be dosed at 10mg three times a week, every other week. Total planned duration of maintenance therapy were to be 3 years.
Patients were to remain on study treatment until they complete the maintenance phase, or until they experience disease progression, unacceptable toxicity, or at the discretion of the Investigator.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 - RVD + Pan | Active comparator | Drug: Revlimid, Drug: Velcade, Drug: dexamethasone, Drug: FarydakRevlimid, Velcade, dexamethasone and Farydak |
| Arm 2 - RVD | Active comparator | Drug: Revlimid, Drug: Velcade, Drug: dexamethasoneRevlimid, Velcade and Dexamethasone |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patient newly diagnosed with multiple myeloma, based on following IMWG 2014 definition (Rajkumar et al 2014):
- Clonal bone marrow plasma cells ≥ 10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events:
- Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder
- Any one or more of the following biomarkers of malignancy:
- Patient with measurable disease defined by at least 1 of the following conditions present at screening:
Key exclusion criteria (21 listed)
- Any concomitant anti-cancer therapy (other than bortezomib/lenalidomide/dexamethasone; bisphosphonates are permitted only if commenced prior to the start of screening period)
- Unresolved diarrhea ≥ CTCAE grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease).
- Allogeneic stem cell transplant recipient presenting with graft versus host disease either active or requiring immunosuppression
- Patient shown intolerance to bortezomib or to dexamethasone or components of these drugs or has any contraindication to one or the other drug, following locally applicable prescribing information
- Patient with rade ≥ 2 peripheral neuropathy or grade 1 peripheral neuropathy with pain on clinical examination at screening
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 |
|---|---|---|
| RevlimidAlso: lenalidomideRevlimid was used with dexamethasone to treat patients with multiple myeloma | Drug | Arm 1 - RVD + Pan, Arm 2 - RVD |
| VelcadeAlso: bortezomibVelcade was a proteasome inhibitor indicated for treatment of patients with multiple myeloma | Drug | Arm 1 - RVD + Pan, Arm 2 - RVD |
| dexamethasoneAlso: DecadronDexamethasone was a steroid used to treat patients with multiple myeloma. | Drug | Arm 1 - RVD + Pan, Arm 2 - RVD |
| FarydakAlso: panobinostat, LBH589FARYDAK® (panobinostat) capsules was a prescription medicine used, in combination with bortezomib and dexamethasone, to treat adults with a type of cancer called multiple myeloma after at least 2 other types of treatment have been tried. | Drug | Arm 1 - RVD + Pan |
Primary outcome
Near Complete Response (nCR)/CR Rate of the Combination of Panobinostat With Bortezomib, Lenalidomide and Dexamethasone (P-RVD) vs RVD in Newly Diagnosed Multiple Myeloma Patients
Time frame: 84 days
6 secondary outcomes
Minimal Residual Disease (MRD) Negativity (mCR) After 4 Cycles of Induction by Next Gen Sequencing
Time frame: Month 3
Best Overall Response Rate (ORR) and MRD Negativity After ASCT and Maintenance
Time frame: Month 3 up to end of study, approximately 3 years.
Depth of Response by International Myeloma Working Group (IMWG) Criteria
Time frame: Day 22 up to end of study, approximately 3 years
Duration of Response
Time frame: From measurable response to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.
Overall Survival
Time frame: 3 years after the last patient is enrolled to the study
Progression Free Survival
Time frame: 3 years after the last patient is enrolled to the study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Revlimid, Velcade and dexamethasone in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 5 sites in United States.
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 15 inclusion and 21 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: stopped early, as of the sponsor's last update on 24 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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 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?
Yes. Results are posted in the registry (first posted 24 Jul 2018). 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?
Near Complete Response (nCR)/CR Rate of the Combination of Panobinostat With Bortezomib, Lenalidomide and Dexamethasone (P-RVD) vs RVD in Newly Diagnosed Multiple Myeloma Patients (time frame: 84 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 24 Jul 2018; AzTrials last refreshed its copy on 7 Nov 2026.