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
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib
Drug: Lenalidomide
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 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).



Secondary Outcome Measures:
  • 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.


Enrollment: 65
Study Start Date: August 2006
Estimated Study Completion Date: December 2014
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:
  • 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00378209

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Massachusetts General Hospital
Celgene Corporation
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Paul Richardson, MD Dana-Farber Cancer Institute
  More Information

No publications provided by Dana-Farber Cancer Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Paul G. Richardson, MD, Principle Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00378209     History of Changes
Other Study ID Numbers: 06-147
Study First Received: September 18, 2006
Results First Received: October 15, 2013
Last Updated: June 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
relapsed multiple myeloma
refractory multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 24, 2014