Clinical Trial Results:
PHASE II MULTICENTER CLINICAL TRIAL TO INVESTIGATE THE EFFICACY AND
SAFETY OF BENDAMUSTINE, DEXAMETHASONE AND THALIDOMIDE IN
RELAPSED OR REFRACTORY MULTIPLE MYELOMA PATIENTS AFTER TREATMENT
WITH LENALIDOMIDE AND BORTEZOMIB OR WHICH ARE INELIGIBLE TO ONE OF
THESE DRUGS.
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Summary
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EudraCT number |
2011-001775-39 |
Trial protocol |
IT |
Global end of trial date |
08 Apr 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Jun 2021
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First version publication date |
24 Jun 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BDT-01-2011
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
U.O. Ematologia & CBMT, Hospital Bolzano
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Sponsor organisation address |
Via Lorenz Böhler 5, Bolzano, Italy,
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Public contact |
DIVISIONE DI EMATOLOGIA E TMO, AZIENDA OSPEDALIERA DI BOLZANO, +39 0471908807, michael.mian@asbz.it
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Scientific contact |
DIVISIONE DI EMATOLOGIA E TMO, AZIENDA OSPEDALIERA DI BOLZANO, +39 0471908807, michael.mian@asbz.it
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Mar 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Apr 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of BDT in relapsed or refractory multiple myeloma as measured by the rate of responses (time frame 18 months).
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Protection of trial subjects |
Pregnancies and suspected pregnancies (including a positive pregnancy test regardless of age or disease state) of a female subject or the female partner of a male subject occurring while the subject is on study drug, or within 30 days of the subject’s last dose of study drug, are considered immediately reportable events. Study drug is to be discontinued immediately and the subject instructed to return any unused portion of the study drug to the Investigator(s).
Patients will receive prophylactic aspirin (acetylsalicylic acid, ASA) (70-100mg) daily unless contraindicated. Patients who are at high risk for a thromboembolic event in whom ASA is contraindicated, the use of low molecular weight heparin or warfarin (or equivalent vitamin K antagonist) to keep the INR in the range of 2-3 may be considered or other anti-thrombotic therapy according to hospital guidelines or physician preference is acceptable.
All concomitant treatments for other pathologies except B-NHL as well as supportive therapies other than anti-cancer treatments are permitted as clinically indicated.
Prophylaxis against hepatitis B reactivation with Lamivudine 100 mg/die from the start of the treatment to one year after the end of the treatment is recommended in HBcAb positive patients.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
31 May 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 30
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Worldwide total number of subjects |
30
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EEA total number of subjects |
30
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
14
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From 65 to 84 years |
16
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85 years and over |
0
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Recruitment
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Recruitment details |
Age ≥ 18 years at the time of signing the informed consent form; Life expectancy of at least 3 months; Relapsed or refractory active MM after treatments containing bortezomib and lenalidomide or ineligible to both of these drugs with detectable myeloma protein in blood or urine; Disease free of prior malignancies for at least 5 years. | ||||||
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Pre-assignment
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Screening details |
No screening details | ||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Single Arm | ||||||
Arm description |
- | ||||||
Arm type |
Single arm study | ||||||
Investigational medicinal product name |
Bendamustine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
60 mg/m2 i.v. days 1, 8, 15
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Investigational medicinal product name |
Thalidomide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
100 mg daily p.o. days 1-28; initial dose of 50mg/day, with an increment to 100mg after the first 15 days of treatment.
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Investigational medicinal product name |
Dexamethasone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
20 mg p.o. days 1,8 , 15, 22
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Four patients were excluded from the present analyses: two were screening failures, one patient died and another one left the country before treatment was started. |
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Baseline characteristics reporting groups
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Reporting group title |
Single Arm
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Single Arm
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Reporting group description |
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Subject analysis set title |
Comparator
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
fictional arm of comparison
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End point title |
Overall Response (ORR) | |||||||||||||||
End point description |
teh overall response rate (ORR) was defined as the number of complete remissions (CR), very good partial remissions (VGPR) and partial responses (PR).
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End point type |
Primary
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End point timeframe |
End of treatment: 6 months after registration.
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Statistical analysis title |
Overall Response Rate | |||||||||||||||
Statistical analysis description |
Percent frequency with 95% confidence interval
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Comparison groups |
Single Arm v Comparator
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Number of subjects included in analysis |
52
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Analysis specification |
Post-hoc
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Analysis type |
other [1] | |||||||||||||||
Method |
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Parameter type |
Frequency | |||||||||||||||
Point estimate |
38.5
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
20.2 | |||||||||||||||
upper limit |
59.4 | |||||||||||||||
| Notes [1] - Was reported the percentage frequency with 95%CI according to Clopper-Pearson binomial confidence intervals. |
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End point title |
Overall Survival | ||||||||||||
End point description |
Overall survival: from the date of registration to the date of death for any cause or date of last clinical control.
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End point type |
Secondary
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End point timeframe |
18 months from registration in the study
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Statistical analysis title |
Estimate Overall survival at 18 months | ||||||||||||
Statistical analysis description |
Estimated OS at 18 months by means of Kaplan-Meier method.
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Comparison groups |
Single Arm v Comparator
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Number of subjects included in analysis |
52
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Analysis specification |
Post-hoc
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Analysis type |
other | ||||||||||||
Method |
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Parameter type |
Kaplan-Meier estimate | ||||||||||||
Point estimate |
0.4
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.22 | ||||||||||||
upper limit |
0.63 | ||||||||||||
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End point title |
Time to treatment failure | ||||||||||||
End point description |
Time from date of registration to treatment interrumption, progression or death for any cause.
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End point type |
Secondary
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End point timeframe |
18 months from date of registration.
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
18 months from date of registration
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4
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Reporting groups
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Reporting group title |
Single arm study
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Reporting group description |
Report of adverse events observed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Date |
Amendment |
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21 Jul 2015 |
Change of the principal investogator, Prolongation of the enrolment period. Prolongation of the insurance period. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
