- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01979276
Study of Pomalidomide, Dexamethasone, and Romidepsin for Rel/Ref Myeloma (Romi Poma)
A Phase I/II Study of Pomalidomide (CC-4047®), Dexamethasone and Romidepsin in Patients With Relapsed or Refractory Multiple Myeloma (Romi Poma)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This phase I/II study is a treatment program for patients with relapsed or refractory multiple myeloma. Up to 48 patients will be enrolled. Phase I will follow a 3+3 dose escalation design to find the maximum tolerated dose of romidepsin in combination with pomalidomide and dexamethasone.
In Phase I, subjects will receive:
- Pomalidomide 4mg daily by mouth on days 1-21 of a 28-day cycle
- Dexamethasone 40mg by mouth on days 1, 8, 15 and 22 of a 28-day cycle
- Romidepsin intravenously (9 mg/m2, 12 mg/m2, 15 mg/m2 or 18 mg/m2) on days 1 and 15 of a 28-day cycle.
Phase II will expand the number of subjects in the MTD arm of the trial until 48 subjects are enrolled. In Phase II, subjects subjects will receive:
- Pomalidomide 4mg daily by mouth on days 1-21 of a 28-day cycle
- Dexamethasone 40mg by mouth on days 1, 8, 15 and 22 of a 28-day cycle
- Romidepsin intravenously on days 1 and 15 of a 28-day cycle at the Maximum Tolerated Dose determined by Phase I
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10065
- Weill Cornell Medical College
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Laboratory test results within these ranges:
g. Serum potassium ≥ 3.8 mmol/L h. Serum magnesium >1.8 mg/dL
- Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to start of study drug(s) and again with 24 hours of prescribing pomalidomide (prescriptions must be filled within 7 days).
- Females of child bearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before starting pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy.
- able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- 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;
- Uncontrolled hypertension, i.e., blood pressure (BP) of ≥160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or
- 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.
- Any coexisting medical problem or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial.
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking pomalidomide.)
- Subjects with any condition, including the presence of laboratory abnormalities, which in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- Use of any other experimental drug or therapy within 14 days of baseline.
- Subjects with a history of development of erythema nodosum, if characterized by a desquamating rash, while taking thalidomide, lenalidomide, pomalidomide or similar drugs.
- Concurrent use of other anti-cancer agents or treatment.
- Concomitant use of CYP3A4 inhibitors (See Appendix D)
- Prior therapy with romidepsin, thalidomide or pomalidomide
- Central nervous system or meningeal involvement
- Patients taking drugs leading to significant QT prolongation
- Known hypersensitivity to thalidomide or lenalidomide
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Pomalidomide, Romidepsin, Dexamethasone
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
|
Romidepsin intravenously on days 1 and 15 of a 28-day cycle
Pomalidomide 4mg daily by mouth on days 1-21 of a 28-day cycle
Dexamethasone 40mg by mouth on days 1, 8, 15 and 22 of a 28-day cycle
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD) of Romidepsin in Combination With Pomalidomide and Dexamethasone
Time Frame: During the duration of the study (from first to last dose of study drug, on average ten 28-day cycles)
|
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
Time Frame: From baseline to cycle of maximum response, which occurred on average after 2 cycles; 1 cycle = 28 days
|
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 Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Time to Disease Progression (Progression Free Survival)
Time Frame: From start of treatment, to date of disease progression (on average, ten 28-day cycles)
|
From start of treatment, to date of disease progression (on average, ten 28-day cycles)
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Ruben Niesvizky, MD, Weill Medical College of Cornell University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Antibiotics, Antineoplastic
- Dexamethasone
- Pomalidomide
- Romidepsin
Other Study ID Numbers
- 1306014005
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Myeloma
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
-
National Cancer Institute (NCI)Active, not recruitingSmoldering Multiple Myeloma | Refractory Multiple Myeloma | DS Stage I Multiple Myeloma | DS Stage II Multiple Myeloma | DS Stage III Multiple MyelomaUnited States
-
Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
Clinical Trials on Romidepsin
-
CelgeneCompletedCarcinoma, Renal Cell | Prostatic NeoplasmsUnited States, United Kingdom
-
CelgeneCompletedCarcinoma, Renal Cell | Neoplasm MetastasisUnited States
-
National Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)CompletedLymphomaUnited States
-
Ohio State University Comprehensive Cancer CenterNational Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)CompletedGastrointestinal Stromal Tumor | Recurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Adult Rhabdomyosarcoma | Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal... and other conditions
-
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NCI)CompletedLymphoma | Myelodysplastic Syndromes | Leukemia | Myelodysplastic/Myeloproliferative NeoplasmsUnited States
-
University of ChicagoNational Cancer Institute (NCI)WithdrawnOvarian CancerUnited States
-
National Cancer Institute (NCI)TerminatedNeoplasms | Mycosis Fungoides | Cutaneous T-Cell LymphomaUnited States
-
National Cancer Institute (NCI)TerminatedRecurrent Adult Diffuse Large Cell Lymphoma | Recurrent Mantle Cell LymphomaUnited States