Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Bortezomib

Romidepsin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Histone Deacetylase Inhibitors

Enzyme Inhibitors

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.

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.

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.

Tina Neilson

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.

Trial of Romidepsin and Bortezomib for Multiple Myeloma

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

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.

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.

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.

Maximum observed concentration of Romidepsin

Time to maximum observed concentration of Romidepsin

Total volume of distribution of Romidepsin

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.

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.

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.

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.

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

Celgene

Romidepsin + Bortezomib

Age, Continuous

Sex: Female, Male

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

Other

Race/Ethnicity, Customized

Status 0

Status 1

Status 2

Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects a patient. The scale ranges from 0 (fully active) to 5 (dead). 0=Fully active without restriction; 1= Restricted in physically strenuous activity; 2= Ambulatory, capable of all selfcare.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Associate Director, Clinical Trials Disclosure

Intent-to-Treat (ITT) population of patients defined as all patients who receive at least one dose of romidepsin and bortezomib. However efficacy data was not analyzed due to the early termination of the study.

Count of Participant Best Overall Response As Assessed by the Investigator

At least 1 TEAE

At least 1 drug-related TEAE

At least 1 Romidepsin-related TEAE

At least 1 Bortezomib-related TEAE

At least 1 >=Grade 3 TEAE

At least 1 Grade 4 TEAE

At least 1 serious TEAE

At least 1 TEAE leading to discontinuation

At least 1 TEAE leading to death

Safety population of participants who took at least one dose of drug.

Participants With Treatment-emergent Adverse Events (TEAEs)

Each patient enrolled in the PK portion underwent one PK sampling period on Day 1 of Cycle 1, following the administration of Bortezomib and 1-hour IV infusion of romidepsin 8mg/m\^2.

Romidepsin 8 mg/m^2 + Bortezomib

Each patient enrolled in the PK portion underwent one PK sampling period on Day 1 of Cycle 1, following the administration of Bortezomib and 1-hour IV infusion of romidepsin 10mg/m\^2.

Romidepsin 10 mg/m^2 + Bortezomib

A subset of participants from the lead investigator's site had PK samples taken.

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

Maximum Observed Concentration (Cmax)

Time to Maximum Observed Concentration (Tmax)

Terminal Half-life (t1/2)

Total Clearance (CL)

Total Volume of Distribution (Vz)

Intent to treat population. Analysis was not performed due to early termination of the study.

Kaplan Meier Estimate for Time to Progression Assessed by the Investigator

Intent to treat population. However efficacy data was not analyzed due to the early termination of the study.

Spots Global Cancer Trial Database for Trial of Romidepsin and Bortezomib for Multiple Myeloma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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