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Trial registered on ANZCTR


Registration number
ACTRN12618000028202
Ethics application status
Approved
Date submitted
14/12/2017
Date registered
12/01/2018
Date last updated
20/11/2019
Date data sharing statement initially provided
17/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 2, open label trial of guadecitabine (SGI-110) in patients with T-cell lymphoma
Scientific title
A phase 2, open label trial to evaluate safety, tolerability and efficacy of guadecitabine (SGI-110) in patients with T-cell lymphoma
Secondary ID [1] 293616 0
Nil known
Universal Trial Number (UTN)
Trial acronym
STELLAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
T-cell lymphoma 305876 0
Condition category
Condition code
Cancer 305075 305075 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Guadecitabine (SGI-110) 60mg/m2 administered by treating clinician subcutaneously (SC) daily for five days (days 1-5) in 28-day treatment cycles. Treatment should be administered for at least six cycles in the absence of disease progression requiring alternative therapy. Treatment will continue indefinitely if tolerated for as long as patient derives benefit (i.e. complete remission, partial remission or stable disease).
Intervention code [1] 299872 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 304251 0
Safety and tolerability of guadecitabine administration in patients with T-cell lymphoma, assessed by adverse events identified via treating clinician review of patient at protocol-specified assessments and data linkage to medical records
Timepoint [1] 304251 0
At two years after commencement of treatment
Primary outcome [2] 304252 0
Overall response rate (ORR = complete response [CR] + partial response [PR]) to guadecitabine in patients with T-cell lymphoma, assessed by PET/CT scan
Timepoint [2] 304252 0
At two years after commencement of treatment
Secondary outcome [1] 341370 0
Progression free survival of patients with T-cell lymphoma treated with guadecitabine
Timepoint [1] 341370 0
At two years after commencement of treatment
Secondary outcome [2] 341371 0
Overall response rate (ORR = complete response [CR] + partial response [PR]) to guadecitabine in the subgroup of patients with angioimmunoblastic T-cell lymphoma, assessed by PET/CT scan
Timepoint [2] 341371 0
At two years after commencement of treatment

Eligibility
Key inclusion criteria
1) Age >18 years old
2) ECOG performance status 0-3.
3) Histologically confirmed diagnosis of a mature T-cell neoplasm, as defined by the 2016 World Health Organisation (WHO) classification system and including (but not restricted to):
a) Anaplastic large cell lymphoma (ALCL), ALK positive or negative
b) Angioimmunoblastic T-cell lymphoma (AITL)
c) Cutaneous T-cell lymphomas (CTCL) including mycosis fungoides (MF) and Sezary syndrome (SS).
d) Enteropathy associated T-cell lymphoma (EATL)
e) Hepatosplenic T-cell lymphoma (HSTL)
f) Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS)
g) T-cell prolymphocytic leukaemia (T-PLL)
4) Measurable disease as defined by disease presentation utilising standard response criteria for systemic (Cheson et al, Blood 2014) or cutaneous disease (Olsen et al, J Clin Oncol 2011).
5) Either:
a) Subjects with relapsed or refractory disease who are unsuitable for high-dose therapy and/or autologous stem cell transplantation in the opinion of the investigator.
b) Subjects with relapsed or refractory disease despite high-dose therapy and/or prior stem cell transplantation.
c) Subjects with newly diagnosed and previously untreated disease who are unfit to receive CHOP/CHOP-like therapy or the disease specific standard of care in the opinion of the investigator.
6) An interval of at least two weeks since treatment with chemotherapy, immunotherapy or biological therapy prior to enrolment. Corticosteroids up to 20mg per prednisolone equivalent per day are permitted for non-lymphoma indications and autoimmune manifestations of lymphoma (e.g. haemolysis).
7) Life expectancy > 3 months.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Prior treatment with guadecitabine or other DNA hypomethylating agent (e.g. azacitidine, decitabine).
2) Hypersensitivity to guadecitabine , azacitidine, decitabine or their excipients.
3) Second malignancy currently requiring active therapy except:
a. Breast or prostate cancer stable on or responding to endocrine therapy.
b. Pre-existing or concurrently diagnosed MDS (including chronic myelomonocytic leukaemia), or AML with bone marrow blasts <31%.
c. Non-melanomatous skin cancers such as basal or squamous cell carcinomas.
4) Patients with known active central nervous system involvement.
5) Renal impairment with creatinine clearance (as estimated by the Cockroft-Gault or other medically acceptable formula) <30ml/min.
6) Liver cirrhosis / chronic liver disease Child-Pugh B or C; total serum bilirubin >2.5x upper limit of normal (ULN), except for subjects with Gilbert’s syndrome for whom the direct bilirubin is <2.5 ULN.
7) Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection not controlled on antiviral therapy. Inactive hepatitis carrier status or low viral hepatitis titre on antivirals is permitted.
8) Inability to understand and comply with study procedures, or unable to provide written informed consent before any study-specific procedure.
9) Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all antibiotics; or advanced pulmonary disease requiring >2 litres per minute (LPM) oxygen.
10) Known illness or condition that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol.
11) Any uncontrolled intercurrent medical condition or laboratory abnormality, which would in the opinion of the investigator make participation unsafe.
12) Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures during the study and for at least 3 months after completing treatment and must agree not to become pregnant or father a child while receiving treatment with guadecitabine and for at least 3 months after completing treatment.

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)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
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
Sample size has been pragmatically determined and 20 patients are expected to be registered on the study in 24 months. With 20 evaluable patients, the maximum standard error for the overall response rate after six cycles of induction is 11.2%. This is considered to be a suitable level of precision for a phase II pilot study.
95% confidence intervals will be reported for ORR in the first six (induction) cycles for all patients and also for those patients in the AITL subgroup. A Bayesian approach will also be adopted to monitor and report the posterior probability distributions for ORR should such interim reports be required by the DMSC.

Recruitment
Recruitment status
Recruiting
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,VIC
Recruitment hospital [1] 9567 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 9569 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 18322 0
2139 - Concord
Recruitment postcode(s) [2] 18320 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 298228 0
Commercial sector/Industry
Name [1] 298228 0
ASTEX Pharmaceuticals Inc.
Address [1] 298228 0
4420 Rosewood Drive, Suite 200
Pleasanton, CA 94588
Country [1] 298228 0
United States of America
Primary sponsor type
Hospital
Name
Monash Health
Address
246 Clayton Road
Clayton, VIC 3168
Country
Australia
Secondary sponsor category [1] 297346 0
None
Name [1] 297346 0
Address [1] 297346 0
Country [1] 297346 0
Other collaborator category [1] 279867 0
Hospital
Name [1] 279867 0
Concord Hospital
Address [1] 279867 0
Hospital Rd
Concord NSW 2139
Country [1] 279867 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299237 0
Monash Health Human Research Ethics Committee A
Ethics committee address [1] 299237 0
246 Clayton Road
Clayton, VIC 3168
Ethics committee country [1] 299237 0
Australia
Date submitted for ethics approval [1] 299237 0
14/11/2017
Approval date [1] 299237 0
18/12/2017
Ethics approval number [1] 299237 0
HREC/17/MonH/555

Summary
Brief summary
The purpose of this study is to test the safety, tolerability and anti-tumour activity of the research study drug, guadecitabine.

Who is it for?
You may be eligible for this study if you are an adult who has been diagnosed with T-cell non-Hodgkin lymphoma, which has (a) not been treated, (b) been deemed unsuitable for standard therapy or (c) have relapsed or refractory disease.

Study details
All participants will receive subcutaneous injections of guadecitabine for the first 5 days of a 28 day treatment cycle. Treatments will be given for at least 6 of these 28 day cycles. This is a safety and efficacy trial, so any adverse events will be recorded and the effect of the study treatment on the lymphoma will be monitored using a PET or CT scan.

This study will provide information about this study drug and allow subsequent study of this potential treatment for T-cell non-Hodgkin lymphoma.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79758 0
A/Prof Jake Shortt
Address 79758 0
Department of Haematology
Level 4, Monash Medical Centre
246 Clayton Road
Clayton, VIC 3168
Country 79758 0
Australia
Phone 79758 0
+61 3 9594 4044
Fax 79758 0
+61 3 9594 6495
Email 79758 0
jake.shortt@monashhealth.org
Contact person for public queries
Name 79759 0
Ms Micheleine Uhe
Address 79759 0
Haematology Research
Level 1, McCulloch House, Monash Medical Centre
246 Clayton Rd, Clayton VIC 3168
Country 79759 0
Australia
Phone 79759 0
+61 3 9594 4044
Fax 79759 0
+61 3 9594 6495
Email 79759 0
micheleine.uhe@monashhealth.org
Contact person for scientific queries
Name 79760 0
A/Prof Jake Shortt
Address 79760 0
Department of Haematology
Level 4, Monash Medical Centre
246 Clayton Road
Clayton, VIC 3168
Country 79760 0
Australia
Phone 79760 0
+61 3 9594 4044
Fax 79760 0
+61 3 9594 6495
Email 79760 0
jake.shortt@monashhealth.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not currently planned to share IPD but this may change in future
What supporting documents are/will be available?
No other documents available
Summary results
No Results