A Trial Evaluating Efficacy & Safety of RVD +/- Panobinostat in Transplant Eligible, Newly Diagnosed Multiple Myeloma (NDMM) (PANORAMA4)
Primary Purpose
Multiple Myeloma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Revlimid
Velcade
dexamethasone
Farydak
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring multiple myeloma, farydak, panobinostat, LBH589, ASCT, transplant
Eligibility Criteria
Key Inclusion Criteria:
- 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
- >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
Key Exclusion Criteria:
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
- 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.
Sites / Locations
- David Geffen School of Medicine at UCLA UCLA
- Memorial West Cancer Center Memorial Cancer Institute
- Northside Hospital Central Research Dept.
- Oncology Hematology West Nebraska Cancer Specialists dbaNebraska Cancer Specialists
- Brooke Army Medical Center Hematology/Oncology
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Arm 1 - RVD + Pan
Arm 2 - RVD
Arm Description
Revlimid, Velcade, dexamethasone and Farydak
Revlimid, Velcade and Dexamethasone
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Minimal Residual Disease (MRD) Negativity (mCR) After 4 Cycles of Induction by Next Gen Sequencing
MRD negativity by Clonal Sequencing (ClonoSEQTM) assay (Adaptive Biotechnologies)
Best Overall Response Rate (ORR) and MRD Negativity After ASCT and Maintenance
ORR (CR + PR) and MRD negativity after ASCT and maintenance
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)
Duration of Response
Overall Survival
Progression Free Survival
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02720510
Brief Title
A Trial Evaluating Efficacy & Safety of RVD +/- Panobinostat in Transplant Eligible, Newly Diagnosed Multiple Myeloma (NDMM)
Acronym
PANORAMA4
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2018
Overall Recruitment Status
Terminated
Why Stopped
A study was terminated due to low enrollment.
Study Start Date
June 14, 2016 (Actual)
Primary Completion Date
May 22, 2017 (Actual)
Study Completion Date
May 22, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
multiple myeloma, farydak, panobinostat, LBH589, ASCT, transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 - RVD + Pan
Arm Type
Active Comparator
Arm Description
Revlimid, Velcade, dexamethasone and Farydak
Arm Title
Arm 2 - RVD
Arm Type
Active Comparator
Arm Description
Revlimid, Velcade and Dexamethasone
Intervention Type
Drug
Intervention Name(s)
Revlimid
Other Intervention Name(s)
lenalidomide
Intervention Description
Revlimid was used with dexamethasone to treat patients with multiple myeloma
Intervention Type
Drug
Intervention Name(s)
Velcade
Other Intervention Name(s)
bortezomib
Intervention Description
Velcade was a proteasome inhibitor indicated for treatment of patients with multiple myeloma
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Other Intervention Name(s)
Decadron
Intervention Description
Dexamethasone was a steroid used to treat patients with multiple myeloma.
Intervention Type
Drug
Intervention Name(s)
Farydak
Other Intervention Name(s)
panobinostat, LBH589
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Minimal Residual Disease (MRD) Negativity (mCR) After 4 Cycles of Induction by Next Gen Sequencing
Description
MRD negativity by Clonal Sequencing (ClonoSEQTM) assay (Adaptive Biotechnologies)
Time Frame
Month 3
Title
Best Overall Response Rate (ORR) and MRD Negativity After ASCT and Maintenance
Description
ORR (CR + PR) and MRD negativity after ASCT and maintenance
Time Frame
Month 3 up to end of study, approximately 3 years.
Title
Depth of Response by International Myeloma Working Group (IMWG) Criteria
Description
Rate of Very Good Partial Response (VGPR), Complete Response (CR) and Stringent Complete Response (sCR)
Time Frame
Day 22 up to end of study, approximately 3 years
Title
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.
Title
Overall Survival
Time Frame
3 years after the last patient is enrolled to the study
Title
Progression Free Survival
Time Frame
3 years after the last patient is enrolled to the study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
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
>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
Key Exclusion Criteria:
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
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
David Geffen School of Medicine at UCLA UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Memorial West Cancer Center Memorial Cancer Institute
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33028
Country
United States
Facility Name
Northside Hospital Central Research Dept.
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Oncology Hematology West Nebraska Cancer Specialists dbaNebraska Cancer Specialists
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68124
Country
United States
Facility Name
Brooke Army Medical Center Hematology/Oncology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
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
Learn more about this trial
A Trial Evaluating Efficacy & Safety of RVD +/- Panobinostat in Transplant Eligible, Newly Diagnosed Multiple Myeloma (NDMM)
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