Study of Pomalidomide, Dexamethasone, and Romidepsin for Rel/Ref Myeloma

NCT01979276 | Terminated Phase 1 Results

• 1 other identifier: 1306014005
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial is for subjects with multiple myeloma that has returned after treatment (relapsed) or did not respond to prior treatment (refractory). The study is in two parts, Phase I and Phase II. Phase I will determine the maximum tolerated dose of romidepsin in combination with pomalidomide and dexamethasone. The purpose of Phase II is to evaluate the effectiveness of combining romidepsin with pomalidomide and dexamethasone. The hypothesis is that overall response in a cohort of patients treated with romidepsin + pomalidomide + dexamethasone will be 60 percent.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Romidepsin in Combination With Pomalidomide and Dexamethasone

  Establish a maximum tolerated dose (MTD) of romidepsin in combination with pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (phase I)

  During the duration of the study (from first to last dose of study drug, on average ten 28-day cycles)

• Efficacy of Study Regimen Combination

  The efficacy (as assessed by clinical response) of the combination of pomalidomide (CC-4047®) and romidepsin as therapy for patients with relapsed or refractory multiple myeloma (MM) (phase II portion) was evaluated using the IMWG Response Criteria for disease assessment. The best response was reported. (Criteria can be found at the following link, due to length and complexity of the response criteria: http://imwg.myeloma.org/international-myeloma-working-group-imwg-uniform-response-criteria-for-multiple-myeloma/)

  From baseline to cycle of maximum response, which occurred on average after 2 cycles; 1 cycle = 28 days

Secondary Outcomes (1)

• Time to Disease Progression (Progression Free Survival)

  From start of treatment, to date of disease progression (on average, ten 28-day cycles)

Study Arms (1)

Pomalidomide, Romidepsin, Dexamethasone

EXPERIMENTAL

Pomalidomide, 4 mg by mouth daily on days 1-21 of 28 day cycle Dexamethasone, 40 mg by mouth on days 1, 8, 15, and 22 of 28 day cycle Romidepsin, IV on days 1 and 15 of 28 day cycle, dose level to be determined Dexamethasone

Drug: Romidepsin; Drug: pomalidomide; Drug: Dexamethasone

Interventions

Romidepsin DRUG

Romidepsin intravenously on days 1 and 15 of a 28-day cycle

Pomalidomide, Romidepsin, Dexamethasone

pomalidomide DRUG

Pomalidomide 4mg daily by mouth on days 1-21 of a 28-day cycle

Pomalidomide, Romidepsin, Dexamethasone

Dexamethasone DRUG

Dexamethasone 40mg by mouth on days 1, 8, 15 and 22 of a 28-day cycle

Pomalidomide, Romidepsin, Dexamethasone

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• histologically confirmed multiple myeloma.
• measurable disease as defined by \> 0.5 g/dL serum monoclonal protein, \>0.1 g/dL serum free light chains, \>0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s).
• relapsed or refractory multiple myeloma as defined by progression of disease either after prior therapy or lack of response to currently used therapy
• relapsed or progressive disease after at least 3 prior therapeutic treatments or regimens for multiple myeloma.
• refractory to bortezomib and lenalidomide
• \>18 years at the time of signing the informed consent form.
• life expectancy of \> 3 months.
• Karnofsky performance status \> 70%, or \> 60% if due to bony involvement of multiple myeloma
• normal organ and marrow function as defined below:
• Absolute Neutrophil Count \> 1,000 cells/mm3 for Phase I, \> 750 cells/mm3 for Phase II
• Platelet Count \> 75,000/mm3 for Phase I, \> 50, 000/mm3 for Phase II
• AST/ Serum SGOT \< 3.0 x upper limits of normal
• ALT/ Serum SGPT \< 3.0 x upper limit of normal
• Serum creatinine \< 2.0 mg/dL
• Serum total bilirubin \< 1.5 x upper limit of normal

You may not qualify if:

• Subjects with non-secretory Multiple Myeloma (no measurable monoclonal protein or plasmacytoma(s), free light chains, and/or M-spike in blood or urine).
• Patients with a prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ≥ 3 years.
• Any known cardiac abnormalities such as:
• Congenital long QT syndrome
• QTc interval ≥ 480 milliseconds
• Myocardial infarction within 6 months of C1D1. Subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 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 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 subject in whom there is doubt, the subject 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 (see Appendix E) and/or ejection fraction \<40% by 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;
• Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
• Any Known seropositivity for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
• Any active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Celgene Corporation: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

romidepsin; pomalidomide; 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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Jennifer Hess
• Organization: Weill Cornell Medical College

jmh2004@med.cornell.edu

646-962-9440

Study Officials

• Ruben Niesvizky, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: October 25, 2013
• First Posted: November 8, 2013
• Study Start: November 1, 2013
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: June 6, 2018
• Results First Posted: January 31, 2018

Record last verified: 2018-05

Locations

US (1)