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Bortezomib, Lenalidomide, and Dexamethasone Combination Therapy for Patients With Relapsed or Relapsed and Refractory Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
Celgene Corporation
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Paul G. Richardson, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00378209
First received: September 18, 2006
Last updated: June 6, 2014
Last verified: June 2014

September 18, 2006
June 6, 2014
August 2006
October 2012   (final data collection date for primary outcome measure)
The Proportion of Patients Alive and Without Progressive Disease (PD) for ≥6 Months [ Time Frame: 6 months after therapy ] [ Designated as safety issue: No ]

Response assessed by the European Group for Blood and Marrow Transplant (EBMT) criteria, modified to include nCR and VGPR from the international uniform response criteria (IMWG).

Progressive disease (PD) required one or more of the following:

>25% increased in serum monoclonal paraprotein (must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation) >25% increased in 24-hour urinary light chain excretion (must also be an absolute increase of at least 200 mg/24 h and confirmed on a repeat investigation) >25% increased in plasma cells in a bone marrow aspirate or on trephine biopsy (must also be an absolute increase of at least 10%) Definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas.

Development of new bone lesions or soft tissue plasmacytomas (not including compression fracture).

Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.8 mmol/L not attributable to any other cause).

Evaluate time to progression following bortezomib, lenalidomide and dexamethasone combination therapy treatment in patients with relapsed or refractory multiple myeloma.
Complete list of historical versions of study NCT00378209 on ClinicalTrials.gov Archive Site
  • Objective Response Rate [ Time Frame: Assessed every cycle for up to 8 cycles and best response was reported ] [ Designated as safety issue: No ]

    Response assessed by the European Group for Blood and Marrow Transplant (EBMT) criteria, modified to include nCR and VGPR from the international uniform response criteria (IMWG).

    Objective response was defined by the achievement of at least Partial Response (PR) or better (CR-complete response, nCR-near complete response, and VGPR-very good partial response).

  • Duration of Response [ Time Frame: Assessed at a median follow-up of 44 months ] [ Designated as safety issue: No ]
    Duration of response will be measured as the time from initiation of a response to first documentation of disease progression or death, or date last known progression-free and alive for those who have not progressed or died.
  • Progression Free Survival [ Time Frame: aassesed at a median follow-up of 44 months ] [ Designated as safety issue: No ]
    Progression-free survival is defined as the time from registration to the disease progression or death from any cause, censored at date last known progression-free for those who have not progressed or died.
Evaluate the objective response rate, the duration of response, the progression free and overall survival, the tolerability and toxicity.
Not Provided
Not Provided
 
Bortezomib, Lenalidomide, and Dexamethasone Combination Therapy for Patients With Relapsed or Relapsed and Refractory Multiple Myeloma
Am Open-Label Phase II Study of the Safety and Efficacy of Bortezomib, Lenalidomide, and Dexamethasone Combination Therapy for Patients With Relapsed or Relapsed and Refractory Multiple Myeloma

The purpose of this study is to evaluate the effectiveness and side effects of the bortezomib, lenalidomide and dexamethasone combination in relapsed or relapsed and refractory multiple myeloma. Each of these drugs are approved by the U.S Food and Drug Administration, but have not been approved in the combination for treating patients in this setting.

  • Participants took the study medication in the clinic on Cycle 1 day 1. Each treatment cycle lasted three weeks. They took the lenalidomide (capsules) every day for the first two weeks only (days 1-14). They took dexamethasone (tablets) on Day 1, 2, 4, 5, 8, 9, 11 and 12 and came to the outpatient treatment center for intravenous bortezomib on Day 1, 4, 8 and 11. The third week of the cycle was a rest period and the participant did not take any study medication.
  • Certain tests and procedures were performed throughout each treatment cycle at definitive time periods. These tests included: medical history update, physical/neurological examination, skeletal survey (x-rays or scan), blood samples, urine samples, optional bone marrow aspiration/tissue biopsy, 12-lead ECG, and MRI/CT (if needed).
  • It was expected that participants were going to complete at least 8 cycles of the study, which adds up to 168 days. If the participant completed the first 8 cycles, had stable or responding disease and had not experienced bad side effects, they were allowed to continue treatment on a maintenance schedule, detailed in the protocol, at the study doctor's discretion.
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: Bortezomib
    Given intravenously on days 1,4,8 and 11 of a 21-day cycle for a minimum of 8 cycles.
  • Drug: Lenalidomide
    Taken orally once a day for 2 weeks (days 1-14) of a 21-day cycle for a minimum of 8 cycles
  • Drug: Dexamethasone
    Taken orally on days 1,2,4,5,8,9,11,and 12 of a 21-day cycle for a minimum of 8 cycles
Experimental: lenalidomide, dexamethasone, bortezomib combination
Participants took the study medication in the clinic on Cycle 1 day 1. Each treatment cycle lasted three weeks. They took the lenalidomide (capsules) every day for the first two weeks only (days 1-14). They took the dexamethasone (tablets) on Day 1, 2, 4, 5, 8, 9, 11 and 12 and came to the outpatient treatment center for intravenous bortezomib on Day 1, 4, 8 and 11. The third week of the cycle was a rest period and the participant did not take any study medication.
Interventions:
  • Drug: Bortezomib
  • Drug: Lenalidomide
  • Drug: Dexamethasone
Richardson PG, Xie W, Jagannath S, Jakubowiak A, Lonial S, Raje NS, Alsina M, Ghobrial IM, Schlossman RL, Munshi NC, Mazumder A, Vesole DH, Kaufman JL, Colson K, McKenney M, Lunde LE, Feather J, Maglio ME, Warren D, Francis D, Hideshima T, Knight R, Esseltine DL, Mitsiades CS, Weller E, Anderson KC. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood. 2014 Mar 6;123(10):1461-9. doi: 10.1182/blood-2013-07-517276. Epub 2014 Jan 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
65
December 2014
October 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of multiple myeloma based on standard diagnostic criteria or by the new International Myeloma Foundation 2003 Diagnostic Criteria
  • Relapsed or relapsed and refractory disease after receiving between 1 and 3 prior regimens
  • Negative serum or urine pregnancy test
  • Age 18 years or older
  • Karnofsky performance status of 60 or greater

Exclusion Criteria:

  • Grade 2 or greater peripheral neuropathy within 14 days before enrollment
  • Renal insufficiency (serum creatinine > 2.5 mg/dL)
  • Evidence of mucosal or internal bleeding and/or platelet refractory
  • ANC < 1000 cells/mm3
  • Hemoglobin < 8.0 g/dL
  • AST or ALT greater than or equal to 2 x ULN
  • Concomitant therapy medications that include corticosteroids
  • Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Clinically relevant active infection or serious co-morbid medical conditions
  • Prior malignancy (within last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or breast cancer, in situ prostate cancer
  • Pregnant or breast-feeding
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Uncontrolled diabetes mellitus
  • Hypersensitivity to acyclovir or similar anti-viral drug
  • POEMS syndrome
  • Known HIV infection
  • Known active hepatitis B or C viral infection
  • Known intolerance to steroid therapy
  • Subjects with primary refractory disease, defined as progression during initial treatment
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00378209
06-147
Not Provided
Paul G. Richardson, MD, Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
  • Brigham and Women's Hospital
  • Massachusetts General Hospital
  • Celgene Corporation
  • Millennium Pharmaceuticals, Inc.
Principal Investigator: Paul Richardson, MD Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP