Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
An open label, multicentre, randomised, parallel group phase II selection trial to identify the optimal starting dose of bendamustine (60 versus 100 mg/m2) when given in combination with thalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma
Acronym
MUKone
Study hypothesis
The primary objective of this trial is to determine the optimum dose of bendamustine when combined with thalidomide and dexamethasone (BTD) in the treatment of relapsed/refractory multiple myeloma, based on response rates, tolerability and progression-free survival.
On 13/08/2012 the target number of participants was changed from 98 to 92.
On 23/08/2012 the overall trial end date was changed from 01/05/2012 to 10/07/2013.
Ethics approval
Not provided at time of registration
Study design
Open-label multicentre randomised parallel group phase II two-stage selection trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Multiple myeloma
Intervention
Arm A: Bendamustine (60), thalidomide, dexamethasone -
Bendamustine: Intravenous at 60 mg/m2/day on days 1 and 2 (30 - 60 minute infusion each day)
Thalidomide: Oral at 100 mg/day on days 1 - 28
Dexamethasone: Oral at 20 mg/day on days 1 - 4 and 15 - 18
Arm B: Bendamustine (100), thalidomide, dexamethasone -
Bendamustine: Intravenous at 100 mg/m2/day on days 1 and 2 (30 - 60 minute infusion each day)
Thalidomide: Oral at 100 mg/day on days 1 - 28
Dexamethasone: Oral at 20 mg/day on days 1 - 4 and 15 - 18
Each cycle is repeated at 28 days. Patients continue treatment until maximum response plus 2 cycles. Assuming tolerability, a minimum of 6 and maximum of 9 cycles will be given.
Patients will be followed up every 12 weeks for one year after the entry of the last patient (i.e. minimum of 1 year, maximum 2 years).
Intervention type
Drug
Phase
Phase II
Drug names
Bendamustine, thalidomide, dexamethasone
Primary outcome measure
1. Proportion of patients achieving at least a partial response (as defined by the Modified International Working Group [IWG] Uniform Response Criteria) within six cycles of treatment, measured within 6 months of start of treatment, i.e., 18 months post-first patient
2. Proportion of patients successfully able to receive their second cycle of bendamustine within six weeks of receiving their first cycle, measured within 6 months of start of treatment, i.e., 18 months post-first patient
3. Progression-free survival, measured at 12 months post-randomisation, i.e., 24 months post first patient
Secondary outcome measures
1. Maximum response rate
2. Overall response rate
3. Response duration
4. Time to next treatment
5. Proportion of patients successfully receiving six cycles of treatment with no dose reductions or delays
6. Safety and toxicity
7. Feasibility of stem cell harvest following treatment (in eligible refractory patients)
All measured within 12 months of randomisation, i.e., within 24 months post-first patient
Overall trial start date
01/09/2010
Overall trial end date
10/07/2013
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current inclusion criteria as of 13/08/2012:
1. Aged greater than or equal to 18 years, either sex
2. Histologically confirmed multiple myeloma (MM) with measurable disease parameters requiring therapy for relapsed or refractory disease
3. Unsupported platelet count >75 x 109/L within 48 hours before registration
4. Absolute neutrophil count >1.5 x 109/L within 48 hours before registration. GCSF is permitted for no more than 7 days prior to registration.
5. Able to provide written informed consent
6. Performance status (Eastern Cooperative Oncology Group [ECOG]) 0 - 3
7. Life expectancy at least 3 months
Previous inclusion criteria until 13/08/2012:
1. Aged greater than or equal to 18 years, either sex
2. Histologically confirmed multiple myeloma (MM) with measurable disease parameters requiring therapy for relapsed or refractory disease
3. Able to provide written informed consent
4. Performance status (Eastern Cooperative Oncology Group [ECOG]) 0 - 3
5. Life expectancy at least 3 months
6. Serum bilirubin less than 1.5 times upper limit of normal
7. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than 2.5 times upper limit of normal
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
92 (95 patients recruited by end of recruitment on 13/07/2012)
Participant exclusion criteria
Current exclusion criteria as of 13/08/2012:
1. Pregnancy, lactation or women of child-bearing potential unwilling to use adequate and highly effective method of contraception whilst receiving treatment and for 12 months after treatment has finished as defined by the Thalidomide Pregnancy Prevention Programme
2. Patients with non-secretory MM
3. Relapsed on previous bendamustine therapy
4. Serum bilirubin >2.0 times ULN within 14 days before registration
5. Serum ALT/AST > 2.5 times ULN within 14 days before registration
6. Patient has a calculated or measured creatinine clearance less than 10 mL/minute within 14 days before enrolment
7. Patient has greater than or equal to grade 2 peripheral neuropathy within 14 days before enrolment
8. Any history of hypersensitivity to any of the study medications or excipients
9. Seropositive for human immunodeficiency virus (HIV), or active hepatitis A, B or C infection
10. Previous or concurrent malignancies at other sites, with the exception of appropriately treated localised epithelial skin or cervical cancer. Patients with histories (greater than or equivalent to 12 months) of other cured tumours may be entered.
11. Serious medical or psychiatric illness likely to interfere with participation in this clinical study
12. Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
13. Subjects who have received an investigational medicinal product within 28 days of study entry
14. Steroid treatment totally greater than 160mg dexamethasone, or equivalent, in the 14 days prior to registration
15. Major surgery less than 30 days before start of treatment
16. Yellow fever vaccination within 3 months before registration
17. Current infections, especially involving leukocytopenia
Previous exclusion criteria until 13/08/2012:
1. Pregnancy, lactation or women of child-bearing potential unwilling to use adequate and highly effective method of contraception whilst receiving treatment and for 12 months after treatment has finished as defined by the Thalidomide Pregnancy Prevention Programme
2. Subjects with evidence of clinically unstable disease, as determined by medical history, clinical laboratory tests, electrocardiogram (ECG) results, and physical examination that, in the Investigator's opinion, preclude entry into the study
3. Any history of hypersensitivity to any of the study medications or excipients
4. Patients with non-secretory MM
5. Patient has a platelet count less than 40 x 10^9/L within 14 days before enrolment
6. Patient has an absolute neutrophil count less than 1.0 x 10^9/L within 14 days before enrolment
7. Patient has a calculated or measured creatinine clearance less than 10 mL/minute within 14 days before enrolment
8. Patient has greater than or equal to grade 2 peripheral neuropathy within 14 days before enrolment
9. Seropositive for human immunodeficiency virus (HIV), or active hepatitis A, B or C infection
10. Serious medical or psychiatric illness likely to interfere with participation in this clinical study
11. Previous or concurrent malignancies at other sites, with the exception of appropriately treated localised epithelial skin or cervical cancer. Patients with remote histories (greater than 5 years) of other cured tumours may be entered.
12. Poorly controlled hypertension or diabetes mellitus or other serious medical or psychiatric conditions that could interfere with adherence to or completion of this study
13. Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
14. Subjects who have received an investigational medicinal product within 30 days of study entry
Recruitment start date
27/01/2012
Recruitment end date
25/06/2012
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University of Leeds
Leeds
LS2 9JT
United Kingdom
Sponsor information
Organisation
University of Leeds (UK)
Sponsor details
c/o Dr Neville Young
Quality Assurance Manager - Clinical Trials
University of Leeds and Leeds Teaching Hospitals NHS Trust
Research & Development
34 Hyde Terrace
Leeds
LS2 9LN
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Myeloma UK
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2015 results in https://www.ncbi.nlm.nih.gov/pubmed/25891006