Panobinostat/Velcade in Multiple Myeloma

NCT00891033 | Terminated Phase 1 DMC

• 1 other identifier: HCI32829
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple myeloma (MM) accounts for approximately 1% of all malignancies and 10% of hematological tumors, representing the second most frequently occurring hematological malignancy in the United States. At any one time, 50,000 people suffer from MM, and approximately 15,000 are diagnosed each year. The median age is approximately 65 years, although occasionally MM occurs in the second decade of life. Bortezomib and panobinostat intravenous (IV) are active agents in multiple myeloma and appear to work through different biochemical pathways, suggesting that there may be a synergistic effect using the combination. Both compounds have shown anabolic bone effect, which has been associated to significant anti-myeloma activity. Primary objectives:

• To assess the toxicity of bortezomib combined with one of 4 doses of panobinostat IV in patients with relapsed/refractory multiple myeloma, and
• To find the most appropriate doses of bortezomib and panobinostat IV in the combination. Secondary objective:
• To assess the effect of bortezomib in combination with panobinostat IV on inducing osteoblast activation in patients with relapsed/refractory myeloma.

Conditions

Multiple Myeloma

Keywords

cancer

Outcome Measures

Primary Outcomes (1)

• Toxicity of bortezomib combined with one of 3 doses of panobinostat IV as measured by the occurrence of dose-limiting toxicity (DLT)

  DLT is defined as at least 2 of 6 patients within a group experiencing greater than or equal to grade 3 non-hematologic toxicity or greater than or equal to grade 4 hematologic toxicity.

  up to 42 days (two 21-day cycles)

Study Arms (4)

Cohort 1

EXPERIMENTAL

1 mg/m2 IV Bortezomib on days 1, 4, 8, and 11 of Cycles 1 and 2 and 5 mg/m2 IV Panobinostat on days 1 and 8 of Cycle 2.

Drug: Bortezomib (Velcade); Drug: Panobinostat

Cohort 2

EXPERIMENTAL

1 mg/m2 IV Bortezomib on days 1, 4, 8, and 11 of Cycles 1 and 2 and 10 mg/m2 IV Panobinostat on days 1 and 8 of Cycle 2.

Drug: Bortezomib (Velcade); Drug: Panobinostat

Cohort 3

EXPERIMENTAL

1 mg/m2 IV Bortezomib on days 1, 4, 8, and 11 of Cycles 1 and 2 and 15 mg/m2 IV Panobinostat on days 1 and 8 of Cycle 2.

Drug: Bortezomib (Velcade); Drug: Panobinostat

Cohort 4

EXPERIMENTAL

1 mg/m2 IV Bortezomib on days 1, 4, 8, and 11 of Cycles 1 and 2 and 20 mg/m2 IV Panobinostat on days 1 and 8 of Cycle 2.

Drug: Bortezomib (Velcade); Drug: Panobinostat

Interventions

Bortezomib (Velcade) DRUG

During the study Bortezomib will be administered intravenously as a 3-5 second bolus IV injection, at a dose of 1.0 mg/m2 on days 1, 4, 8, and 11 of each 21-day treatment cycle.

Also known as: Velcade

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Panobinostat DRUG

During the study, panobinostat IV will be administered intravenously as once daily on (day 1 and 8 of the 21 day cycle 2 and beyond). Patients enrolled on first group will receive 5 mg/m2 panobinostat IV, second group 10 mg/m2 panobinostat IV, third group 15 mg/m2 panobinostat IV and the fourth group 20 mg/m2 panobinostat IV. Each infusion of panobinostat will be administered over 30 minutes.

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

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

You may qualify if:

• Patients with relapsed/refractory multiple myeloma to at least one line of prior therapy
• Male or female patients aged ≥ 18 years old
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Patients are allowed to receive growth factors (erythropoietin hormones, GCSF and GMCSF)
• Patients must meet the following laboratory criteria:
• ANC ≥ 1.5 x 109/L
• Hemoglobin ≥ 9 g/dl
• Platelets ≥ 100x 109/L
• Calculated CrCl \> 50 mL/min (MDRD Formula)
• AST and ALT ≤ 2.5 x ULN
• Serum bilirubin \< 2.0 x ULN
• Albumin \> 3.0 g/dl
• Serum potassium ≥ LLN for the institution
• Total serum calcium \[corrected for serum albumin\] or ionized calcium ≥LLN, for the institution
• Serum magnesium ≥ LLN for the institution

You may not qualify if:

• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
• Patients who have received Velcade within 2 months of enrollment
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat IV treatment
• Peripheral neuropathy \> grade 2.
• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
• Patients with congenital long QT syndrome
• 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 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)
• 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

Sponsors & Collaborators

• University of Arkansas: lead
• Novartis: collaborator

Study Sites (1)

Myeloma Institute for Research and Therapy University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms

Interventions

Bortezomib; Panobinostat

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; 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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydroxamic Acids; Hydroxylamines; Amines; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mauizio Zangari, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2009
• First Posted: April 30, 2009
• Study Start: April 1, 2009
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: February 23, 2015

Record last verified: 2015-02

Locations

US (1)