Phase II, Single-Center, Oral Panobinostat in Combination With Lenalidomide and Dexamethasone in Multiple Myeloma (MM)

NCT01651039 | Completed Phase 2 Results DMC

• 2 other identifiers: GCO 12-0469CLBH589DUS85T
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical research study is to find out the effects of a drug called panobinostat (LBH589) when given to people like you with multiple myeloma in combination with the drugs lenalidomide and dexamethasone. The safety of this combination of drugs will also be studied. Your physical state, changes in the state of your multiple myeloma, and laboratory findings taken while on-study will help us decide if panobinostat combined with dexamethasone and lenalidomide is safe and effective. This goal of this study therefore is to determine the activity of the combination of panobinostat thrice weekly every other week, lenalidomide, and weekly dexamethasone in a similar group of subjects. The doses of lenalidomide and dexamethasone will be that which is approved by the FDA for multiple myeloma and you will take each drug at a specific frequency over a 4 week (28 day) period. This period is called a "study cycle".

Conditions

Multiple Myeloma

Keywords

Panobinostat; Lenalidomide; Dexamethasone

Outcome Measures

Primary Outcomes (2)

• The Best Overall Response Rate (ORR)

  The primary endpoint will be the best overall response rate (ORR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  up to 4 years

• Overall Response Rate for Len Refractory Patients

  The primary endpoint will be the best overall response rate (ORR)

  up to 4 years

Secondary Outcomes (6)

• Response Rates

  up to 4 years

• Response Rates for Len Refractory Patients

  up to 4 years

• Clinical Benefit Rate

  up to 4 years

• Clinical Benefit Rate for Len Refractory Patients

  up to 4 years

• Disease Control Rate

  up to 4 years

Study Arms (1)

Panobinostat, Lenalidomide and Dexamethasone

EXPERIMENTAL

All patients will receive oral panobinostat, lenalidomide and dexamethasone as per protocol.

Drug: Panobinostat; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Panobinostat DRUG

Each cycle is 28 days. Panobinostat will be given 20 mg: Days 1,3,5,15,17,19.

Also known as: LBH589

Panobinostat, Lenalidomide and Dexamethasone

Lenalidomide DRUG

Each cycle is 28 days. Lenalidomide will be given 25 mg: Days 1-21.

Also known as: Revlimid

Panobinostat, Lenalidomide and Dexamethasone

Dexamethasone DRUG

Each cycle is 28 days. Dexamethasone will be given for patients 75 years old and younger a dose of 40 mg on Days 1, 8 and 15. Dexamethasone will be given for patients older than 75 years old, 20 mg on Days 1, 8 and 15.

Panobinostat, Lenalidomide and Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Patients must have a history of symptomatic multiple myeloma according to the International Myeloma Working Group criteria (IMWG, 2003), as defined as the following three criteria:
• Clonal plasma cells \>10% on bone marrow biopsy
• A monoclonal protein (paraprotein) in either serum or urine(except in cases of non-secretory myeloma)
• Evidence of end-organ damage felt related to the plasma cell disorder (related organ or tissue impairment, ROTI, commonly referred to by the acronym "CRAB"):
• Hypercalcemia serum Ca ≥ 11.5 mg/dL or
• Renal insufficiency attributable to myeloma. Serum creatinine \> 2mg/dL
• Anemia: Normochromic, normocytic with a hemoglobin value \> 2g/dL below the lower limit of normal or a hemoglobin \<10 g/dL
• Bone lesions (lytic lesions, severe osteopenia or pathologic fractures
• Patients must have received at least one prior line of therapy. For example; One prior line of therapy may consist of all predetermined components of induction followed by autologous stem cell transplantation and maintenance.
• Patient has relapsed or relapsed/refractory MM.
• Relapsed is defined as the development of disease progression following the achievement of stable disease (SD) or better to the most recent anti-MM regimen.
• Refractory is defined as experiencing less than a partial response (PR) to or progressive disease (PD) within 6 months after completion of the most recent anti-MM regimen.
• Patients must currently have measureable disease, as defined as:
• a. Serum M protein ≥ 1.0 g/dl (≥ 10 mg/l)
• Urine M protein ≥ 200 mg/24h

You may not qualify if:

• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
• History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible but should be discussed with Novartis prior to enrollment)
• Any history of ventricular fibrillation or torsade de pointes
• Bradycardia defined as HR\< 50 bpm. Patients with pacemakers are eligible if resting HR ≥ 50 bpm.
• Screening ECG with a QTc \> 450 msec
• Right bundle branch block + left anterior hemiblock (bifascicular block)
• Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug
• Other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
• Impairment of GI function or GI disease that may significantly alter the absorption of panobinostat
• Patients with diarrhea \> CTCAE grade 2
• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
• Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
• Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies.
• Patients who have received either immunotherapy within \< 8 weeks; chemotherapy within \< 4 weeks; or radiation therapy to \> 30% of marrow-bearing bone within \< 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.

Sponsors & Collaborators

• Ajai Chari: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Panobinostat; Lenalidomide; Dexamethasone

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)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Dr. Ajai Chari
• Organization: Icahn School of Medicine at Mount Sinai

ajai.chari@mountsinai.org

212-241-7873

Study Officials

• Ajai Chari, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 24, 2012
• First Posted: July 26, 2012
• Study Start: July 1, 2012
• Primary Completion: December 21, 2016
• Study Completion: December 21, 2016
• Last Updated: April 9, 2018
• Results First Posted: April 9, 2018

Record last verified: 2018-03

Locations

US (1)