Trial of Romidepsin and Bortezomib for Multiple Myeloma

NCT00765102 | Terminated Phase 2 Results

• 1 other identifier: GPI-08-0006
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 12

Brief Summary

This is a phase II, open-label, multicenter, dual-strata study designed to evaluate the efficacy and safety of IV romidepsin given in combination with IV bortezomib for multiple myeloma (MM) patients with refractory or relapsed disease. Patients will be enrolled into one of two strata, bortezomib-resistant or bortezomib non-resistant.

Conditions

Multiple Myeloma

Keywords

Multiple Myelonoma; Romidepsin; Bortezomib

Outcome Measures

Primary Outcomes (1)

• Count of Participant Best Overall Response As Assessed by the Investigator

  Complete Response: disappearance of monoclonal protein from blood and urine, and disappearance of soft tissue plasmacytomas, \<5% plasmas cells in marrow and no increase of lytic bone lesions. Very Good Partial Response: disappearance of plasmacytomas, no increase of lytic bone lesions, serum and urine M-protein not detectable by immunofixation, other. Partial Response: \>=50% decrease in serum monoclonal protein, and in soft tissue plasmacytomas, no increase of lytic bone lesions, other. Minimal Response (MR): ≥ 25% to ≤ 49% decrease in serum monoclonal protein, and in size of plasmacytomas, no increase of lytic bone lesions, other. Stable Disease: Less than MR, but not PD Progressive Disease(PD):\>25% increase in serum monoclonal paraprotein, or \>25% plasma cells in marrow, or \>25% increase in 24-hour urinary light chain excretion or increase in existing lytic bone lesions or soft tissue plasmacytomas or new bone lesions or soft tissue plasmacytomas, or hypercalcemia.

  up to 8 months

Secondary Outcomes (12)

• Participants With Treatment-emergent Adverse Events (TEAEs)

  up to 9 months

• Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-∞)

  Day 1 (cycle 1): 1 hour prior to romidepsin administration, 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours after initiation of romidepsin infusion

• Maximum Observed Concentration (Cmax)

  Day 1 (cycle 1): 1 hour prior to romidepsin administration, 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours after initiation of romidepsin infusion

• Time to Maximum Observed Concentration (Tmax)

  Day 1 (cycle 1): 1 hour prior to romidepsin administration, 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours after initiation of romidepsin infusion

• Terminal Half-life (t1/2)

  Day 1 (cycle 1): 1 hour prior to romidepsin administration, 0.25, 0.5, 1, 2, 3, 4, 6, and 24 hours after initiation of romidepsin infusion

Study Arms (1)

Romidepsin + Bortezomib

EXPERIMENTAL

Romidepsin was given as an infusion on Days 1, 8 and 15 of each 28-day cycle. Bortezomib was administered twice a week for two consecutive weeks (Days 1, 4, 8 and 11) followed by a 17-day rest period. Patients were treated to a maximum response plus two additional cycles or a maximum of eight cycles.

Drug: Bortezomib; Drug: Romidepsin

Interventions

Bortezomib DRUG

Bortezomib was administered at a dose of 1.0 mg/m\^2 as an intravenous (IV) push over 3 to 5 seconds twice weekly for 2 consecutive weeks (Days 1, 4, 8 and 11) of each 28-day cycle. On days that bortezomib and romidepsin were administered together, bortezomib was administered prior to the romidepsin infusion. Patients were treated to a maximum response plus two additional cycles or a maximum of eight cycles.

Also known as: VELCADE®

Romidepsin + Bortezomib

Romidepsin DRUG

Romidepsin initially was administered at a dose of 10 mg/m\^2 as a 1-hour intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle. Based on the occurrence of Grade 3 thrombocytopenia at this dose level, the dose was reduced by protocol amendment to 8 mg/m\^2.

Also known as: ISTODAX®, depsipeptide, FK228

Romidepsin + Bortezomib

Eligibility Criteria

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

You may qualify if:

• Patients must fulfill all of the following criteria to be eligible for study participation:
• Male or female patients aged ≥ 18 years old
• Has given voluntary written informed consent before any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care
• Previously diagnosed with multiple myeloma (MM) based on standard criteria as follows:
• Major criteria:
• Plasmacytomas on tissue biopsy.
• Bone marrow plasmacytosis (\>30% plasma cells).
• Monoclonal immunoglobulin spike on serum electrophoresis IgG \>3.5 g/dL or IgA \>2.0 g/dL; kappa or lambda light chain excretion \>1 g/day on 24 hour urine protein electrophoresis
• Minor criteria:
• Bone marrow plasmacytosis (10 to 30% plasma cells)
• Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria
• Lytic bone lesions.
• Normal IgM \<50 mg/dL, IgA \<100 mg/dL or IgG \<600 mg/dL
• Any of the following sets of criteria will confirm the diagnosis of MM:
• Any two of the major criteria

You may not qualify if:

• Patients are ineligible for entry if any of the following criteria are met:
• Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or thalidomide, lenalidomide, arsenic trioxide, bortezomib, or glucocorticosteroids within 3 weeks prior to the first dose of romidepsin
• Prior major surgery within 3 weeks prior to the first day of treatment
• Use of any investigational agent within 4 weeks of study entry
• Prior therapy with romidepsin
• Any known cardiac abnormalities such as:
• Congenital long QT syndrome;
• QTc interval ≥ 500 milliseconds;
• Myocardial infarction within 6 months of Day 1. Subjects with a history of myocardial infarction between 6 and 12 months prior to the first day of cycle one who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate;
• Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min);
• Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
• An ECG recorded at screening showing evidence of cardiac ischemia (ST depression depression of ≥2 mm, measured from isoelectric line to the ST segment). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
• Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction \<40% by Multi Gated Acquisition Scan (MUGA scan) or \<50% by echocardiogram and/or MRI;
• A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD);
• Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes;

Sponsors & Collaborators

• Celgene: lead

Study Sites (12)

Loma Linda University Cancer Center

Loma Linda, California, 92354, United States

Location

Desert Cancer Care, Inc

Rancho Mirage, California, 92270, United States

Location

Santa Barbara Hematology Oncology Medical Group, Inc.

Santa Barbara, California, 93105, United States

Location

James R Berenson, MD, Inc.

West Hollywood, California, 90069, United States

Location

Georgia Cancer Specialists I, PC

Atlanta, Georgia, 30341, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Mecklenburg Medical Group

Charlotte, North Carolina, 28204, United States

Location

Baylor Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Dallas Oncology Consultants, P.A.

Duncanville, Texas, 75137, United States

Location

Oncology Consultants, P.A

Houston, Texas, 77024, United States

Location

Central Utah Clinic, PC

Provo, Utah, 84604, United States

Location

Virginia Mason Medical Centre

Seattle, Washington, 98101, United States

Location

Related Publications (1)

• Berenson J, et al. A phase II study of a 1-hour infusion of romidepsin combined with bortezomib for multiple myeloma (MM) patients with relapsed or refractory disease. Presented at 2009 ASCO Annual Meeting, May 29-June 2, 2009, Orlando FL. Abstract No. e10908. J Clin Oncol 2009;27(15s)

  BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; romidepsin; Depsipeptides

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)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• Tina Neilson

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: September 30, 2008
• First Posted: October 2, 2008
• Study Start: September 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: November 25, 2019
• Results First Posted: December 20, 2012

Record last verified: 2019-11

Locations

US (12)