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
Overview
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 6
- Locations
- 5
- Primary Endpoint
- 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
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 74 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
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:
Arms & Interventions
Arm 1 - RVD + Pan
Revlimid, Velcade, dexamethasone and Farydak
Intervention: Revlimid (Drug)
Arm 1 - RVD + Pan
Revlimid, Velcade, dexamethasone and Farydak
Intervention: Velcade (Drug)
Arm 1 - RVD + Pan
Revlimid, Velcade, dexamethasone and Farydak
Intervention: dexamethasone (Drug)
Arm 1 - RVD + Pan
Revlimid, Velcade, dexamethasone and Farydak
Intervention: Farydak (Drug)
Arm 2 - RVD
Revlimid, Velcade and Dexamethasone
Intervention: Revlimid (Drug)
Arm 2 - RVD
Revlimid, Velcade and Dexamethasone
Intervention: Velcade (Drug)
Arm 2 - RVD
Revlimid, Velcade and Dexamethasone
Intervention: dexamethasone (Drug)
Outcomes
Primary Outcomes
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 Outcomes
- Minimal Residual Disease (MRD) Negativity (mCR) After 4 Cycles of Induction by Next Gen Sequencing(Month 3)
- Best Overall Response Rate (ORR) and MRD Negativity After ASCT and Maintenance(Month 3 up to end of study, approximately 3 years.)
- Depth of Response by International Myeloma Working Group (IMWG) Criteria(Day 22 up to end of study, approximately 3 years)
- Duration of Response(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.)
- Progression Free Survival(3 years after the last patient is enrolled to the study)
- Overall Survival(3 years after the last patient is enrolled to the study)