Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000219785
Ethics application status
Approved
Date submitted
18/12/2012
Date registered
25/02/2013
Date last updated
7/07/2020
Date data sharing statement initially provided
17/12/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Panobinostat maintenance in patients with multiple myeloma that have achieved less than complete remission following autologous stem cell transplantation.
Scientific title
A 2-Stage Phase II study of panobinostat in myeloma patients with less than complete remission (CR) following high-dose chemotherapy conditioned autologous stem cell transplantation (ASCT).
Secondary ID [1] 281695 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple myeloma less than complete remission following Autologous Stem Cell Transplant 287983 0
Condition category
Condition code
Blood 288366 288366 0 0
Haematological diseases
Cancer 288804 288804 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will commence treatment with oral panobinostat 45mg three times per week every other week as part of a 4-week (28 day) treatment cycle. Patients will be treated for 6 cycles and then assessed for response. If after 6 cycles patients have not achieved a very good partial response (VGPR) or CR they will cease panobinostat. Patients achieving the required response will continue on panobinostat until disease progression or unacceptable toxicity.
Intervention code [1] 286232 0
Treatment: Drugs
Comparator / control treatment
uncontrolled
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288538 0
To determine the rate of conversion to CR/VGPR achieved with post-ASCT maintenance with panobinostat determined by blood tests and medical tests.
Timepoint [1] 288538 0
Patients are to complete 6 cycles and response will be determined.
Secondary outcome [1] 300408 0
To evaluate the safety and toxicity of panobinostat following ASCT for MM, to document progression free survival and overall survival and to evaluate quality of life pre-panobinostat and while on treatment. This will be determined by clinical assessment.
Timepoint [1] 300408 0
Patients will be assessed at the start of each cycle of treatment.

Eligibility
Key inclusion criteria
Inclusion criteria at registration - pre-ASCT
1. Age > 18 years
2. Diagnosis of multiple myeloma
3. Must have been previously exposed to thalidomide, and/or lenalidomide and/or bortezomib containing induction regimen pre-ASCT (no more than 12 months total prior standard-dose chemotherapy)
4. No previous high-dose chemotherapy or ASCT
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
6. > 2 X 10^6 CD34+ stem cells available for infusion
7. Normal liver and kidney function (within 2 x the institutional upper limit of normal)
8. Written informed consent
Inclusion criteria to commence panobinostat post-ASCT
10. Have reached Day 42 post-ASCT with evidence of haematology recovery (neutrophils > 1.5 x 10^9/L, platelets unsupported > 50 x 10^9/L
11. Have failed to achieve CR and without progressive disease at 6 to 8 weeks post-ASCT
12. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
13. Normal liver and kidney function (within 2 x the institutional upper limit of normal); serum potassium, magnesium, phosphate, sodium, total corrected calcium within normal limits
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with monoclonal gammopathy of uncertain significance (MGUS)
2. Patient has been treated with allogeneic transplant
3. Patient has received any anti-MM therapy after ASCT including but not limited to:
- chemotherapy prior to start of study
- biologic immunotherapy including monoclonal antibodies or experimental therapy prior to start of study
- radiation therapy
4. Patients with progressive MM post-ASCT
5. Patient has received prior treatment with DAC in ihibitors including panobinostat
6. Patient has received an investigational agent of any kind within 28 days of ASCT
7. Patient is taking any anti-cancer therapy concomitantly
8. Patient needs valproic acid within 5 days prior to first administration of panobinostat
9. Patients with evidence of another malignancy not in remission, or history of such a malignancy within the last 3 years (except for treated basal or squamous cell carcinoma,
or in situ cancer of the cervix)
10. Patient has undergone major surgery < 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy to < grade 1 CTCAE 4.0 or baseline
11. Patient has impaired cardiac function, including any one of the following:
- Left Ventricular Ejection Fraction < the lower limit of institutional norm
- Complete left bundle branch block, bifascicular block
- Obligate use of a permanent cardiac pacemaker
- Congenital long QT syndrome
- History or presence of ventricular tachy-arrhythmias
- Resting bradycardia defined as < 50 bpm
- QTcF > 480 msec on screening ECG
- Any clinically significant ST segment and/or T-wave abnormalities
- Presence of unstable atrial fibrillation (ventricular response rate > 100 bpm). Patients with stable atrial fibrillation are allowed in the study provided they do not meet the other cardiac exclusion criteria
- Myocardial infarction or unstable angina pectoris < 6 months prior to starting the study drug
- Congestive cardiac failure (New York Heart Association class III-IV)
- Other clinically significant heart disease and vascular disease (eg. uncontrolled hypertension)
12. Patient is taking medications with relative risk of prolonging the QT interval or inducing torsade de pointes, if such treatment cannot be discontinued or switched to a different medication prior to starting study drug
13. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat, such as:
- ulcerative disease
- uncontrolled nausea
- vomiting
- diarrhoea CTCAE 4.0 Grade > 2 (despite antidiarrheal medications)
- malabsorption syndrome
- obstruction
- stomach and/or small bowel resection
14. Patient has any other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol such as:
- uncontrolled diabetes
- active or uncontrolled infection
- chronic obstructive or chronic restrictive pulmonary disease including dyspnea at rest from any cause
- uncontrolled thyroid dysfunction
- recent, acute or active bleeding
15. Patient has a known history of human immunodeficiency virus (HIV) seropositivity or history of active/treated hepatitis B or C (a test for screening is not required)

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)
All patients will be registered on-study within 4 weeks prior to undergoing ASCT. Each patient will be assigned a unique trial number made up of a two digit site number and a three digit patient number.
At 6-8 weeks post-ASCT eligibility will be confirmed and panobinostat maintenance treatment should be commenced within 10 days
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 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Patient entry in the trial will continue until 10 patients have been enrolled and completed 6 cycles of treatment in stage 1. If less than or equal to two patients respond, the trial will be terminated (achieve CR or VGPR). If two or more patients respond then the trial will proceed to stage 2 and a further 25 patients will be enrolled.
The first major analysis of results will take place after the 10 patients in stage 1 have all completed 6 cycles of therapy. If the study is to continue (i.e. not terminated) the next analysis will take place after all patients have either come off trial (due to failure to respond, death, progression, intolerance or patient choice) or received 12 months of protocol treatment. A further analysis will take place after all patients have had a minimum of 2.5 years follow-up.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/09/2012
Actual
11/09/2012
Date of last participant enrolment
Anticipated
1/09/2014
Actual
17/12/2015
Date of last data collection
Anticipated
14/01/2019
Actual
25/02/2020
Sample size
Target
25
Accrual to date
Final
25
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 333 0
The Alfred Hospital
Recruitment postcode(s) [1] 6132 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 286485 0
Hospital
Name [1] 286485 0
THe Alfred Hospital
Country [1] 286485 0
Australia
Primary sponsor type
Hospital
Name
The Alfred Hospital
Address
Malignant Haematology and Stem Cell Transplantation Service, Ground Floor, South Block, The Alfred Hospital, Commercial Rd, Melbourne, VIC. 3004
Country
Australia
Secondary sponsor category [1] 285276 0
None
Name [1] 285276 0
Address [1] 285276 0
Country [1] 285276 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288560 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 288560 0
Ethics committee country [1] 288560 0
Australia
Date submitted for ethics approval [1] 288560 0
24/05/2012
Approval date [1] 288560 0
06/07/2012
Ethics approval number [1] 288560 0
AH363/11

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 36686 0
Dr Anna Kalff
Address 36686 0
Malignant Haematology and Stem Cell Transplantation Service, The Alfred Hospital, Commercial Rd, Melbourne VIC 3004
Country 36686 0
Australia
Phone 36686 0
+61 3 9076 3571
Fax 36686 0
+61 3 9076 5531
Email 36686 0
[email protected]
Contact person for public queries
Name 36687 0
Anna Kalff
Address 36687 0
Malignant Haematology and Stem Cell Transplantation Service, The Alfred Hospital, Commercial Rd, Melbourne VIC 3004
Country 36687 0
Australia
Phone 36687 0
+61 3 9076 3571
Fax 36687 0
+61 3 9076 5531
Email 36687 0
[email protected]
Contact person for scientific queries
Name 36688 0
Andrew Spencer
Address 36688 0
Malignant Haematology and Stem Cell Transplantation Service, The Alfred Hospital, Commercial Rd, Melbourne VIC 3004
Country 36688 0
Australia
Phone 36688 0
+61 3 9076 3393
Fax 36688 0
+ 61 3 9076 5531
Email 36688 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
individual data will not be shared


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePhase II trial of single-agent panobinostat consolidation improves responses after sub-optimal transplant outcomes in multiple myeloma.2021https://dx.doi.org/10.1111/bjh.17080
EmbaseHistone modifications in drug-resistant cancers: From a cancer stem cell and immune evasion perspective.2023https://dx.doi.org/10.1038/s12276-023-01014-z
N.B. These documents automatically identified may not have been verified by the study sponsor.