A phase 2, open label trial of guadecitabine (SGI-110) in patients with T-cell lymphoma

Phase 2

Completed

• Conditions: T-cell lymphoma; Cancer - Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

• Registration Number: ACTRN12618000028202
• Lead Sponsor: Monash Health

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-01-12
• Study Completion: 2021-12-31
• Last Update Posted: 15 May 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 20

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.

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

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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[At two years after commencement of treatment];Overall response rate (ORR = complete response [CR] + partial response [PR]) to guadecitabine in patients with T-cell lymphoma, assessed by PET/CT scan[At two years after commencement of treatment]

Secondary Outcome Measures

Name	Time	Method
Progression free survival of patients with T-cell lymphoma treated with guadecitabine[At two years after commencement of treatment];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[At two years after commencement of treatment]