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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02386800




Registration number
NCT02386800
Ethics application status
Date submitted
6/03/2015
Date registered
12/03/2015
Date last updated
24/04/2020

Titles & IDs
Public title
CINC424A2X01B Rollover Protocol
Scientific title
Open Label, Multi-center, Phase IV Study of Ruxolitinib or Ruxolitinib and Panobinostat Combination, for Patients Who Have Completed Prior Global Novartis or Incyte Sponsored Studies
Secondary ID [1] 0 0
2014-003527-22
Secondary ID [2] 0 0
CINC424A2X01B
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Myelofibrosis 0 0
Chronic Idiopathic Myelofibrosis 0 0
Post Polycythemia Vera Myelofibrosis 0 0
Post Essential Thrombocythaemia Myelofibrosis 0 0
Steroid Refractory Graft Versus Host Disease 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ruxolitinib tablets or oral pediatric formulation, panobinostat capsules
Treatment: Drugs - ruxolitinib tablets or oral pediatric formulation

Experimental: ruxolitinib monotherapy - ruxolitinib monotherapy. Patients are to use the study treatment based on the parent protocol.

Experimental: combination of ruxolitinib + panobinostat - combination of ruxolitinib and panobinostat. Patients are to use the study treatment based on the parent protocol.


Treatment: Drugs: ruxolitinib tablets or oral pediatric formulation, panobinostat capsules
ruxolitinib tablets or oral pediatric formulation, panobinostat capsules

Treatment: Drugs: ruxolitinib tablets or oral pediatric formulation
ruxolitinib tablets or oral pediatric formulation

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

Outcomes
Primary outcome [1] 0 0
Number of Participants with Adverse Events as a Measure of Safety and Tolerability - Frequency and nature of adverse events and serious adverse events. GvHD Patient Population: At every quarterly visit, the investigator is required to confirm any infections or second primary malignancies under Adverse Events.
Pediatric GvHD population*: At every yearly visit, the investigator is to determine the Tanner staging (if applicable).
*Pediatric GvHD population herein refers to both pediatric and adolescents from parent protocols: CINC424F12201 (REACH-4) and CINC424G12201 (REACH-5).
Adolescent and Pediatric GvHD Patients: height and weight monitoring is required yearly by the investigator until 18 years old
Timepoint [1] 0 0
through study completion estimated to be approximately 12 years
Secondary outcome [1] 0 0
To evaluate clinical benefit as assessed by the investigator - Proportion of patients with clinical benefit as assessed by the investigator at scheduled visits.
Timepoint [1] 0 0
through study completion estimated to be approximately 12 years

Eligibility
Key inclusion criteria
Inclusion criteria:

Patients eligible for inclusion in this study have to meet all of the following criteria:

1. Patient is currently enrolled in a Novartis GDD or GMA-sponsored or Incyte-sponsored
clinical study (where Incyte can delegate the sponsorship to a preferred CRO, if
applicable) that is approved to enroll into this rollover study, and are receiving
either ruxolitinib or combination of ruxolitinib and panobinostat, and fulfilled all
of the requirements of the parent protocol.

2. Patient is currently benefiting from the treatment with ruxolitinib monotherapy or
combination of ruxolitinib and panobinostat, as determined by the investigator

3. Patient has demonstrated compliance, as assessed by the investigator, with the parent
study protocol requirements

4. Willingness and ability to comply with scheduled visits, treatment plans and any other
study procedures

5. Patient currently has no evidence of progressive disease, as determined by the
investigator, following previous treatment with ruxolitinib or combination of
ruxolitinib and panobinostat

6. Written informed consent obtained prior to enrolling in rollover study and receiving
study medication. If consent cannot be expressed in writing, it must be formally
documented and witnessed, ideally via an independent trusted witness.

Note 1: If the patient is a minor, the parent who signs the informed consent for the minor
must be a legally recognized parent or guardian. Where deemed appropriate by the clinician,
and the child's parent or guardian, the child will also be included in the all discussions
about the trials and the minor aged 12 and above assent will be obtained. The parent or
guardian will sign on the designated line on the ICF attesting to the fact that the child
had given consent.

Note 2: if the minor is an adolescent female, she will be informed during the assent
process that for safety purpose, a pregnancy test is required. She will also be told that
if it is positive, she will be counseled and will be assisted in telling her parents. If
the minor does not want to proceed, she will be advised not to sign consent and her
enrollment in this protocol will end.
Minimum age
1 Month
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

Patients eligible for this study must not meet any of the following criteria:

1. Patient has been permanently discontinued from study treatment in the parent study due
to any reason.

2. Patient's indication is currently approved and reimbursed in the local country.

3. Patient has participated in a combination trial other than the panobinostat and
ruxolitinib combination trial (CLBH589X2106), where ruxolitinib was dispensed in
combination with another study medication and until the termination of gestation,
confirmed by a positive hCG laboratory test.

4. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test.

5. Female patients between = 12 and < 18 years of age and of childbearing potential (e.g.
are menstruating) who do not agree to abstinence or, if sexually active, do not agree
to the use of highly effective contraception as defined below, throughout the study
and for up to 30 days after stopping treatment.

Women of childbearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
throughout the study duration inclusive of the 30-day safety follow up. Highly
effective contraception methods include:

- Total abstinence (when this is in line with the preferred and usual lifestyle of
the patient. Periodic abstinence (e.g., calendar, ovulation, symptom-thermal,
post-ovulation methods) and withdrawal are not acceptable methods of
contraception

- Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy or tubal ligation at least six weeks before
taking study treatment. In case of oophorectomy alone, only when the reproductive
status of the woman has been confirmed by follow up hormone level assessment

- Male sterilization (at least 6 months prior to screening). For female patients on
the study the vasectomized male partner should be the sole partner for that
patient.

- Use of oral, injected or implanted hormonal methods of contraception or placement
of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of
hormonal contraception that have comparable efficacy (failure rate <1%), for
example hormone vaginal ring or transdermal hormone contraception.

In case of use of oral contraception women should have been stable on the same pill
for a minimum of 3 months before taking study treatment.

Women are considered post-menopausal and not of childbearing potential if they have
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile
(e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral
oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago.
In the case of oophorectomy alone, only when the reproductive status of the woman has
been confirmed by follow up hormone level assessment is she considered not of
childbearing potential.

6. For patients on the combination of ruxolitinib and panobinostat:

- Women of childbearing potential unwilling to use highly effective methods of
contraception during dosing and for 3 months (female patients of childbearing
potential)

- Female sexual partner(s) of childbearing potential of male participants unwilling
to use highly effective methods of contraception during dosing and for 6 months
after stopping.

- Women of childbearing potential who use hormonal contraceptives and additionally
unwilling to use a barrier method for birth control.Sexually active males
(including vasectomised men) unwilling to use barrier contraception (condom with
spermicide) during intercourse and for 6 months after stopping treatment (in
order to prevent delivery of the drug via seminal fluid).

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
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Darlinghurst
Recruitment hospital [2] 0 0
Novartis Investigative Site - St Leonards
Recruitment hospital [3] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [4] 0 0
Novartis Investigative Site - Wooloongabba
Recruitment hospital [5] 0 0
Novartis Investigative Site - Bedford Park
Recruitment hospital [6] 0 0
Novartis Investigative Site - Box Hill
Recruitment hospital [7] 0 0
Novartis Investigative Site - Clayton
Recruitment hospital [8] 0 0
Novartis Investigative Site - Franston
Recruitment hospital [9] 0 0
Novartis Investigative Site - Perth
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
4102 - Wooloongabba
Recruitment postcode(s) [5] 0 0
5041 - Bedford Park
Recruitment postcode(s) [6] 0 0
3128 - Box Hill
Recruitment postcode(s) [7] 0 0
3168 - Clayton
Recruitment postcode(s) [8] 0 0
3199 - Franston
Recruitment postcode(s) [9] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Antwerpen
Country [2] 0 0
Belgium
State/province [2] 0 0
Brugge
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Belgium
State/province [4] 0 0
Liege
Country [5] 0 0
Bulgaria
State/province [5] 0 0
Pleven
Country [6] 0 0
Bulgaria
State/province [6] 0 0
Plovdiv
Country [7] 0 0
Bulgaria
State/province [7] 0 0
Sofia
Country [8] 0 0
Chile
State/province [8] 0 0
Valparaiso
Country [9] 0 0
Chile
State/province [9] 0 0
Santiago
Country [10] 0 0
China
State/province [10] 0 0
Beijing
Country [11] 0 0
China
State/province [11] 0 0
Zhejiang
Country [12] 0 0
Germany
State/province [12] 0 0
Aachen
Country [13] 0 0
Germany
State/province [13] 0 0
Dresden
Country [14] 0 0
Germany
State/province [14] 0 0
Magdeburg
Country [15] 0 0
Germany
State/province [15] 0 0
Mainz
Country [16] 0 0
Germany
State/province [16] 0 0
Ulm
Country [17] 0 0
Greece
State/province [17] 0 0
GR
Country [18] 0 0
Greece
State/province [18] 0 0
Patras
Country [19] 0 0
Hungary
State/province [19] 0 0
Budapest
Country [20] 0 0
Hungary
State/province [20] 0 0
Debrecen
Country [21] 0 0
Hungary
State/province [21] 0 0
Kaposvar
Country [22] 0 0
Hungary
State/province [22] 0 0
Kecskemet
Country [23] 0 0
Hungary
State/province [23] 0 0
Szeged
Country [24] 0 0
Hungary
State/province [24] 0 0
Szombathely
Country [25] 0 0
Israel
State/province [25] 0 0
Afula
Country [26] 0 0
Israel
State/province [26] 0 0
Jerusalem
Country [27] 0 0
Italy
State/province [27] 0 0
BA
Country [28] 0 0
Italy
State/province [28] 0 0
FI
Country [29] 0 0
Italy
State/province [29] 0 0
MI
Country [30] 0 0
Italy
State/province [30] 0 0
PA
Country [31] 0 0
Italy
State/province [31] 0 0
PV
Country [32] 0 0
Italy
State/province [32] 0 0
RC
Country [33] 0 0
Italy
State/province [33] 0 0
RM
Country [34] 0 0
Italy
State/province [34] 0 0
TO
Country [35] 0 0
Italy
State/province [35] 0 0
VA
Country [36] 0 0
Italy
State/province [36] 0 0
Napoli
Country [37] 0 0
Japan
State/province [37] 0 0
Aichi
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Seocho Gu
Country [39] 0 0
Korea, Republic of
State/province [39] 0 0
Seoul
Country [40] 0 0
Lebanon
State/province [40] 0 0
Beirut
Country [41] 0 0
Mexico
State/province [41] 0 0
Nuevo Leon
Country [42] 0 0
Portugal
State/province [42] 0 0
Lisboa
Country [43] 0 0
Russian Federation
State/province [43] 0 0
Moscow
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Petrozavodsk
Country [45] 0 0
South Africa
State/province [45] 0 0
Gauteng
Country [46] 0 0
South Africa
State/province [46] 0 0
Western Province
Country [47] 0 0
South Africa
State/province [47] 0 0
Pretoria
Country [48] 0 0
Spain
State/province [48] 0 0
Castilla Y Leon
Country [49] 0 0
Spain
State/province [49] 0 0
Catalunya
Country [50] 0 0
Spain
State/province [50] 0 0
Navarra
Country [51] 0 0
Sweden
State/province [51] 0 0
Huddinge
Country [52] 0 0
Sweden
State/province [52] 0 0
Lulea
Country [53] 0 0
Sweden
State/province [53] 0 0
Lund
Country [54] 0 0
Sweden
State/province [54] 0 0
Uddevalla
Country [55] 0 0
Thailand
State/province [55] 0 0
Bangkoknoi
Country [56] 0 0
Thailand
State/province [56] 0 0
Bangkok
Country [57] 0 0
Turkey
State/province [57] 0 0
Sihhiye
Country [58] 0 0
Turkey
State/province [58] 0 0
Istanbul
Country [59] 0 0
Turkey
State/province [59] 0 0
Izmir
Country [60] 0 0
Turkey
State/province [60] 0 0
Talas / Kayseri

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This roll-over protocol allows patients who are still receiving clinical benefit to continue
to be treated from multiple protocols in one program spanning multiple indications during the
completion of the parent study/(ies). The population for the roll-over study should be
consistent with the population defined in the program parent study/(ies). The primary
eligibility criteria for a patient to enter the roll-over protocol is the participation and
completion of a Novartis GDD&GMA/Incyte study with ruxolitinib monotherapy or combination of
ruxolitinib and panobinostat. Efficacy parameters would not be measured; however safety data
and an evaluation of clinical benefit will be collected.

Patients who have completed a prior study with ruxolitinib monotherapy or combination of
ruxolitinib and panobinostat and who are assessed by the Investigator to continue to benefit
from ongoing treatment will be eligible.
Trial website
https://clinicaltrials.gov/show/NCT02386800
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
+41613241111
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02386800