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Multiple MyelomaPhase 2NCT00765102

Trial of Romidepsin and Bortezomib for Multiple Myeloma

A Phase 2 study testing Bortezomib and Romidepsin in people with Multiple Myeloma, run by Celgene at 12 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Bortezomib and Romidepsin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
12 sitesUnited States
Study dates
1 Sep 2008to 1 Mar 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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consent before any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care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.
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  • 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
  • Major criterion 1 plus minor criterion 2, 3, or 4.
  • Major criterion 3 plus minor criterion 1 or 3.
  • Minor criteria 1, 2, and 3 or 1, 2, and 4.
  • Currently has MM with:
  • o Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of >=1 gm/dL and/or urine monoclonal immunoglobulin spike of >=200 mg/24 hours, or evidence of lytic bone disease
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Life-expectancy > 3 months
  • All women of childbearing potential must use an effective barrier method of contraception. Male patients should use a barrier method of contraception during the treatment period and for 3 months thereafter
  • Patients must meet the following laboratory criteria at Baseline (Day 1 of Cycle 1, before study drug administration):
  • Platelet count ≥ 100*10^9/L
  • Absolute neutrophil count ≥ 1.5*10^9/L
  • OR if the bone marrow is extensively infiltrated
  • Platelet count ≥ 75*10^9/L
  • Absolute neutrophil count ≥ 1.0*10^9/L
  • Patients must meet the following laboratory criteria at the Screening visit conducted within 14 days of enrollment (Day 1, Cycle 1):
  • o Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 3.0*upper limit of normal (ULN)
  • Serum bilirubin ≤ 2.0*ULN
  • Calculated or measured creatinine clearance: ≥30 mL/minute. Patient with a creatinine >10mL/min and <30 mL/min due to significant myelomatous involvement of the kidneys may be enrolled in the study after receipt of approval from the lead investigator and sponsor
  • Serum potassium ≥ 3.8 mmol/L
  • Serum magnesium >1.8 mg/dL
  • Serum phosphorus ≥ lower limit of normal (LLN)

Who cannot join

  • 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:
Show all 29Show fewer
  • 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;
  • 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)
  • POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes)
  • Plasma cell leukemia
  • Primary amyloidosis
  • Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
  • Severe hypercalcemia, i.e., serum calcium ≥14 mg/dL (3.5 mmol/L)
  • Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
  • Other concurrent severe and/or uncontrolled medical or psychiatric conditions.
  • Concomitant use of drugs that may cause a prolongation of the QTc
  • Concomitant use of CYP3A4 inhibitors
  • Patients who have hypersensitivity to bortezomib, boron or mannitol
  • Patients who are pregnant or breast-feeding
  • Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Georgia Cancer Specialists I, PC

    Atlanta, Georgia, 30341

  • Center for Cancer and Blood Disorders

    Bethesda, Maryland, 20817

  • Mecklenburg Medical Group

    Charlotte, North Carolina, 28204

  • Baylor Sammons Cancer Center

    Dallas, Texas, 75246

  • Dallas Oncology Consultants, P.A.

    Duncanville, Texas, 75137

  • Oncology Consultants, P.A

    Houston, Texas, 77024

  • Loma Linda University Cancer Center

    Loma Linda, California, 92354

  • Central Utah Clinic, PC

    Provo, Utah, 84604

  • Desert Cancer Care, Inc

    Rancho Mirage, California, 92270

  • Santa Barbara Hematology Oncology Medical Group, Inc.

    Santa Barbara, California, 93105

  • Virginia Mason Medical Centre

    Seattle, Washington, 98101

  • James R Berenson, MD, Inc.

    West Hollywood, California, 90069

Other trials in United States

About this study

Official title: A Phase II Trial of Romidepsin and Bortezomib for Multiple Myeloma Patients With Relapsed or Refractory Disease

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.

Being tested
Bortezomib, Romidepsin
Keywords
Multiple Myelonoma, Romidepsin, Bortezomib
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BortezomibDrug

    Also called VELCADE®

    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.

  • RomidepsinDrug

    Also called ISTODAX®, depsipeptide, FK228

    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.

Study groups in NCT00765102
Study groupRoleWhat they receive
Romidepsin + BortezomibExperimentalRomidepsin 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.
Receives: Drug: Bortezomib; Drug: Romidepsin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: up to 8 months

Secondary outcomes (12)

  1. Participants With Treatment-emergent Adverse Events (TEAEs)

    Counts of participants with TEAEs, and subset by relation to drug, grade of severity, serious, TEAEs leading to discontinuation or leading to death. AEs were graded for severity according to the National Cancer Institute Common Terminology Criteria (NCI CTCAE), V 3.0: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe (prevents normal everyday activities); Grade 4: Life-threatening or disabling; Grade 5: Death.

    Measured: up to 9 months

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

    AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞) of Romidepsin based on plasma samples.

    Measured: 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

  3. Maximum Observed Concentration (Cmax)

    Maximum observed concentration of Romidepsin

    Measured: 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

  4. Time to Maximum Observed Concentration (Tmax)

    Time to maximum observed concentration of Romidepsin

    Measured: 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

  5. Terminal Half-life (t1/2)

    Terminal half-life of Romidepsin

    Measured: 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

  6. Total Clearance (CL)

    Total clearance of Romidepsin

    Measured: 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

  7. Total Volume of Distribution (Vz)

    Total volume of distribution of Romidepsin

    Measured: 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

  8. Kaplan Meier Estimate for Time to Progression Assessed by the Investigator

    Time to progression of disease is defined as the time from initiation of therapy to progressive disease as assessed by the investigator.

    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.

    Disease progression for participants relapsing from a complete response: reappearance of serum or urinary paraprotein on imunofixation, >= 5% plasma cells in the bone marrow aspirate or biopsy, increase in existing lytic bone lesions or soft tissue plasmacytomas or new bone lesions or soft tissue plasmacytomas, development of hypercalcemia.

    Measured: up to month 8

  9. Kaplan Meier Estimate for Time to Response Assessed by the Investigator

    The time to the first response is defined as the time from the initiation of therapy to the first evidence of a confirmed response (complete response, very good partial response, partial response or minimal response).

    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.

    Measured: up to month 8

  10. Kaplan Meier Estimate for Duration of Response Assessed by the Investigator

    Duration of response is defined as the time from first response to progressive disease as assessed by the investigator.

    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.

    Disease progression for participants relapsing from a complete response: reappearance of serum or urinary paraprotein on imunofixation, >= 5% plasma cells in the bone marrow aspirate or biopsy, increase in existing lytic bone lesions or soft tissue plasmacytomas or new bone lesions or soft tissue plasmacytomas, development of hypercalcemia.

    Measured: up to month 8

  11. Kaplan Meier Estimates for Progression-free Survival Assessed by the Investigator

    Progression-free survival is the time from initiation of therapy to progressive disease, removal from study for any reason, death from any cause, or the last follow-up visit, whichever occurs first.

    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.

    Disease progression for participants relapsing from a complete response: reappearance of serum or urinary paraprotein on imunofixation, >= 5% plasma cells in the bone marrow aspirate or biopsy, increase in existing lytic bone lesions or soft tissue plasmacytomas or new bone lesions or soft tissue plasmacytomas, development of hypercalcemia.

    Measured: up to month 8

  12. Kaplan Meier Estimates for Overall Survival

    Overall survival is the time from initiation of therapy to death from any cause.

    Measured: up to month 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Oct 2008 (estimated)
  2. Study start1 Sep 2008
  3. Primary completion1 Mar 2010
  4. Study completion1 Mar 2010

Why it stopped: There was a change in the Sponsor's research strategy; safety concerns were not a factor.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00765102
Sponsor's protocol ID
GPI-08-0006
Status last verified
Nov 2019
First submitted
30 Sep 2008
Last updated
25 Nov 2019
Data monitoring committee
No

Publications

  • 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)

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bortezomib and Romidepsin in people with Multiple Myeloma, run by Celgene at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Count of Participant Best Overall Response As Assessed by the Investigator (time frame: up to 8 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00765102, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2019.

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