A Trial Evaluating Efficacy & Safety of RVD +/- Panobinostat in Transplant Eligible, Newly Diagnosed Multiple Myeloma (NDMM)

NCT02720510 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: CLBH589DUS106
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 5

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.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; farydak; panobinostat; LBH589; ASCT; transplant

Outcome Measures

Primary Outcomes (1)

• 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

  84 days

Secondary Outcomes (6)

• 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.

• Overall Survival

  3 years after the last patient is enrolled to the study

Study Arms (2)

Arm 1 - RVD + Pan

ACTIVE COMPARATOR

Revlimid, Velcade, dexamethasone and Farydak

Drug: Revlimid; Drug: Velcade; Drug: dexamethasone; Drug: Farydak

Arm 2 - RVD

ACTIVE COMPARATOR

Revlimid, Velcade and Dexamethasone

Drug: Revlimid; Drug: Velcade; Drug: dexamethasone

Interventions

Revlimid DRUG

Revlimid was used with dexamethasone to treat patients with multiple myeloma

Also known as: lenalidomide

Arm 1 - RVD + Pan; Arm 2 - RVD

Velcade DRUG

Velcade was a proteasome inhibitor indicated for treatment of patients with multiple myeloma

Also known as: bortezomib

Arm 1 - RVD + Pan; Arm 2 - RVD

dexamethasone DRUG

Dexamethasone was a steroid used to treat patients with multiple myeloma.

Also known as: Decadron

Arm 1 - RVD + Pan; Arm 2 - RVD

Farydak DRUG

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.

Also known as: panobinostat, LBH589

Arm 1 - RVD + Pan

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

David Geffen School of Medicine at UCLA UCLA

Los Angeles, California, 90095, United States

Location

Memorial West Cancer Center Memorial Cancer Institute

Pembroke Pines, Florida, 33028, United States

Location

Northside Hospital Central Research Dept.

Atlanta, Georgia, 30342, United States

Location

Oncology Hematology West Nebraska Cancer Specialists dbaNebraska Cancer Specialists

Omaha, Nebraska, 68124, United States

Location

Brooke Army Medical Center Hematology/Oncology

San Antonio, Texas, 78234, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; Bortezomib; Dexamethasone; Calcium Dobesilate; Panobinostat

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids; Indoles

Limitations and Caveats

This study was terminated prematurely. The reason for study termination was not related to challenges linked to efficacy or safety data but instead, had faced unanticipated challenges with enrollment.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2016
• First Posted: March 28, 2016
• Study Start: June 14, 2016
• Primary Completion: May 22, 2017
• Study Completion: May 22, 2017
• Last Updated: July 24, 2018
• Results First Posted: July 24, 2018

Record last verified: 2018-06

Locations

US (5)