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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00431990




Registration number
NCT00431990
Ethics application status
Date submitted
4/02/2007
Date registered
6/02/2007
Date last updated
12/08/2011

Titles & IDs
Public title
A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma
Scientific title
A Phase I/II Trial of Romidepsin (Depsipeptide) and Bortezomib in Patients With Relapsed Myeloma
Secondary ID [1] 0 0
06/34
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - depsipeptide
Treatment: Drugs - bortezomib
Treatment: Drugs - dexamethasone

Treatment: Drugs: depsipeptide
Cohort 1. Dose escalation, IV, Weeklyx3 in a 4week cycle. Cohort 2A. 12mg/m2, IV, Weeklyx3 in a 4week cycle. Cohort 2B. 12mg/m2, IV, Weeklyx2 in a 3week cycle.

Treatment: Drugs: bortezomib
Cohort 1 and 2A. 3.5mg/m2, IV, day 1, 4, 8, 11 in 28 day cycle. Cohort 2B. 3.5mg/m2, IV, day 1, 4, 8, 11 in 21 day cycle

Treatment: Drugs: dexamethasone
20mg for 2 days with each dose of bortezomib

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Toxicity
Timepoint [1] 0 0
Until progression
Secondary outcome [1] 0 0
Overall response
Timepoint [1] 0 0
Until progression
Secondary outcome [2] 0 0
Time to progression
Timepoint [2] 0 0
Until progression
Secondary outcome [3] 0 0
Overall survival
Timepoint [3] 0 0
Until progression

Eligibility
Key inclusion criteria
1. Patient was previously diagnosed with multiple myeloma based on standard criteria
treated with at least one, but less than 4 lines of therapy, and currently requires
further treatment because of relapse from CR or PD.

2. Patient previously treated with bortezomib will be included in the study, if the
duration of response was >6mths from the completion of therapy.

3. Patient's age is > 18 yrs

4. Patient is, in the investigator's opinion, willing and able to comply with the
protocol requirements.

5. Patient has given voluntary written informed consent.

6. Female patients of child-bearing potential and male patients with female partners of
child-bearing potential, one of whom has not undergone surgical sterilisation must
agree to use 2 simultaneous methods of contraception. For female patients, a negative
pregnancy test is to be performed within 7 days prior to administration of study
drugs.

7. Patient has measurable disease.

- serum monoclonal protein (SEP) > 5 g/L

- serum-free light chains (SFLC) > 100 mg/L

- urine-free light chains (UFLC) > 200 mg/24hr

- measurable soft tissue (not bone) plasmacytoma (STPC)

8. Patient has a Karnofsky performance status =80%.

9. Patient has a life-expectancy >3 months.

10. Patient has the following laboratory values within 14 days before study drug
administration:

- Platelet count =50 × 109/L without transfusion support within 7 days

- Hemoglobin =75 g/L without transfusion support within 7 days

- Absolute neutrophil count (ANC) =0.75 × 109/L without the use of growth factors.

- Corrected serum calcium <14 mg/dL (3.5 mmol/L).

- Serum potassium = 4.0 mmol/L and serum magnesium = 0.85 mmol/L (electrolytes can
be corrected with supplementation. See section 9.7).

- Aspartate transaminase (AST): =2.5 × the upper limit of normal (ULN).

- Alanine transaminase (ALT): =2.5 × the ULN.

- Total bilirubin: =1.5 × the ULN.

- Calculated or measured creatinine clearance: =20 mL/minute.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior severe allergic reactions to bortezomib (Velcade), romidepsin, boron or mannitol

2. Neuropathy > Grade 3 or Neuropathy of Grade 2 with pain > Grade 1 by NCI-CTCAE
criteria (v3.0).

3. Patients with the following cardiac risk factors will be excluded from the study (as
per the previous NCI trials):

- Congenital long QT syndrome

- QTc interval > 480 milliseconds

- Patients who have had a myocardial infarction within 12 months of study entry.

- Patients who have active coronary artery disease, e.g. angina as defined by
Canadian Class II-IV (Appendix 3).

- Patients with an ECG showing evidence of cardiac ischemia (ST depression of = 2
mm).

- Patients with congestive heart failure that meets NYHA Class II to IV definitions
(Appendix 4) and/or ejection fraction < 45% by MUGA scan or < 50% by
echocardiogram and/or MRI.

- Patients with a history of sustained VT, VF, Torsade de Pointes, or cardiac
arrest unless currently addressed with an automatic implantable cardioverter
defibrillator (AICD).

- Patients with dilated, hypertrophic, or restrictive cardiomyopathy from prior
treatment or other causes (in doubt, see ejection fraction criteria above).

- Patients with uncontrolled hypertension, i.e. SBP = 160 mm Hg or DBP = 95 mm Hg.

- Patients with cardiac arrhythmia requiring anti-arrhythmic medication other than
beta blocker or calcium channel blocker. Patients in whom digitalis cannot be
discontinued are excluded from study.

- Patients with Mobitz II second degree heart block, that do not have a pacemaker.

Note: Patients with other cardiac disease may be excluded at the discretion of the
principal investigator following consultation with cardiologist.

4. Pregnancy in female patients

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
8006 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Celgene Corporation
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Janssen-Cilag Ltd.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of the first phase of the study is to determine whether, and at what dose,
depsipeptide, bortezomib and dexamethasone can be safely administered to patients with
Multiple Myeloma. The second phase of the study will establish whether depsipeptide,
bortezomib and dexamethasone is effective in the treatment of patients with multiple myeloma.
The study will also examine the role of maintenance therapy with depsipeptide.
Trial website
https://clinicaltrials.gov/show/NCT00431990
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Simon J Harrison, MBBS, PhD.
Address 0 0
Peter MacCallum Cancer Centre, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Joanne Dean
Address 0 0
Country 0 0
Phone 0 0
613 9656 1111
Fax 0 0
Email 0 0
Joanne.Dean@petermac.org
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00431990