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

NCT00378209 | Completed Phase 2 Results

• 1 other identifier: 06-147
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

relapsed multiple myeloma; refractory multiple myeloma

Outcome Measures

Primary Outcomes (1)

• The Proportion of Patients Alive and Without Progressive Disease (PD) for ≥6 Months

  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).

  6 months after therapy

Secondary Outcomes (4)

• Objective Response Rate

  Assessed every cycle for up to 8 cycles and best response was reported

• Duration of Response

  Assessed at a median follow-up of 44 months

• Progression Free Survival

  aassesed at a median follow-up of 44 months

• Overall Survival

  assesed at a median follow-up of 44 months

Study Arms (1)

lenalidomide, dexamethasone, bortezomib combination

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Bortezomib DRUG

Given intravenously on days 1,4,8 and 11 of a 21-day cycle for a minimum of 8 cycles.

lenalidomide, dexamethasone, bortezomib combination

Lenalidomide DRUG

Taken orally once a day for 2 weeks (days 1-14) of a 21-day cycle for a minimum of 8 cycles

lenalidomide, dexamethasone, bortezomib combination

Dexamethasone DRUG

Taken orally on days 1,2,4,5,8,9,11,and 12 of a 21-day cycle for a minimum of 8 cycles

lenalidomide, dexamethasone, bortezomib combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Massachusetts General Hospital: collaborator
• Celgene Corporation: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 24429336 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Dr. Paul Richardson
• Organization: Dana-Farber Cancer Institute

Paul_Richardson@dfci.harvard.edu

617-632-2104

Study Officials

• Paul Richardson, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: September 18, 2006
• First Posted: September 19, 2006
• Study Start: August 1, 2006
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2016
• Last Updated: November 17, 2016
• Results First Posted: June 9, 2014

Record last verified: 2016-10

Locations

US (2)