Clinical trial NCT00378209: Bortezomib, Lenalidomide, and Dexamethasone Combination Therapy for Patients With Relapsed or Relapsed and Refractory Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: relapsed multiple myeloma
refractory multiple myeloma
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Massachusetts General Hospital
name: Celgene Corporation
name: Millennium Pharmaceuticals, Inc.
First posted: 2006-09-19
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: The Proportion of Patients Alive and Without Progressive Disease (PD) for ≥6 Months
timeFrame: 6 months after therapy
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Assessed every cycle for up to 8 cycles and best response was reported
measure: Duration of Response
timeFrame: Assessed at a median follow-up of 44 months
measure: Progression Free Survival
timeFrame: aassesed at a median follow-up of 44 months
measure: Overall Survival
timeFrame: assesed at a median follow-up of 44 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Paul Richardson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.