Open-Label Extension of Guadecitabine Clinical Studies
Research type
Research Study
Full title
An Open-Label, Multicentre, Extension Study for Subjects who participated in prior Guadecitabine Clinical Studies
IRAS ID
277407
Contact name
Manish Jain
Contact email
Sponsor organisation
Astex Pharmaceuticals, Inc.
Eudract number
2017-004603-52
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
102743, IND Number
Duration of Study in the UK
1 years, 5 months, 28 days
Research summary
Summary of Research
Guadecitabine is study medication being evaluated in patients with haematological malignancies including acute myeloid leukaemia (AML), myelodysplastic syndromes (MDS), and chronic myelomonocytic leukaemia (CMML), and solid tumours including ovarian cancer and hepatocellular carcinoma (HCC). This study is a multicenter, open-label extension study. Participants in a parent study who are benefiting from guadecitabine at the time of database lock will be the potential participants. In the UK, this includes patients with MDS or CMML.
For people who suffer from MDS, their bone marrow does not produce enough healthy blood cells. While MDS is relatively uncommon, the incidence increases with age, therefore it is often more complicated to manage as there is a lessened ability to tolerate intensive treatment due to the presence of one or more non-cancerous diseases that occurs simultaneously with MDS. Patients with MDS have an increased risk of acute leukaemia (a serious and life
threatening blood cancer). Overall survival in patients with MDS is also reduced.CMML is characterised as having too many monocytes, a type of blood cell produced in the bone marrow that helps
the other blood cells remove damaged tissue in the blood. Prognosis is generally poor in CMML patients, with an
average survival of 12 to 19 months.Preliminary data indicate clinical activity of guadecitabine in AML and MDS, with the potential benefits of symptom improvement, improvement in blood counts, decreased need for transfusions, delayed disease progression including progression to AML, delayed need for subsequent anticancer therapy, and prolongation of survival. Hence, benefits of response to treatment may outweigh incremental risks of guadecitabine therapy.
Participants will attend clinic visits on Days 1-5 of each 28-day cycle to receive treatment with guadecitabine, for as long as they continue to benefit from guadecitabine, or until guadecitabine becomes commercially available.
Summary of Final Research
In this Astex Pharmaceuticals, Inc. (Astex) study, SGI-110-12, patients enrolled (called “subjects”) had a blood cancer called acute myeloid leukemia, myelodysplastic syndromes, or chronic myelomonocytic leukemia. Upon completion of data collection on Astex-sponsored original guadecitabine studies, subjects on these studies still benefiting from guadecitabine treatment were provided ongoing guadecitabine treatment on the SGI-110-12 extension study. Guadecitabine doses, determined by study doctors based on the doses subjects received in the original studies, were administered at study centers by study personnel the first 5 days of each 4-week treatment cycle. The goals of this study were to provide ongoing treatment to patients benefitting the treatment and to collect data on guadecitabine’s safety and how long subjects on guadecitabine lived.
On 18 July 2018, the first subject signed an informed consent to be able to participate in this study. The last observation of a subject for this study was on 04 October 2021. Thirty-five subjects were enrolled and received guadecitabine in North America, the European Union, Asian Pacific countries, and Australia. At enrollment, subjects’ average age was 75.3 years, and ages ranged from 27 to 94 years. Twenty subjects (57%) were male. Twenty-four subjects (69%) were white.
While in this study, half of the subjects received more than 7 cycles of treatment, and half received fewer than 7 cycles. Subjects received as few as 1 cycle and as many as 26 cycles.
When Astex stopped this study and the guadecitabine development program, 9 subjects (26%) had died, 7 subjects (20%) had decided to withdraw from the study, and 19 subjects (54%) were withdrawn.
Thirty one subjects (89%) had at least 1 adverse event (AE). The AEs were severe in 15 subjects (43%), life-threatening in 8 subjects (23%), or fatal in 1 subject (3%). The AEs in at least 4 subjects were a low number of a type of blood cell important in fighting infections (8 subjects, 23%), a low number of this type of blood cell plus fever (7 subjects, 20%), lung infection (pneumonia) (6 subjects, 19%), a low number of blood cells that carry oxygen to organs (anemia) and a low number of blood cells that help blood to clot (each, 5 subjects, 14%), and diarrhea and fever (each, 4 subjects, 11%). In 20 subjects (57%), these AEs were considered serious, usually because they resulted in or lengthened hospitalization. The serious AEs in more than 1 subject were a low number of a type of blood cell important in fighting infections plus fever (7 subjects, 20%), lung infection (pneumonia) (6 subjects, 19%), and response to infection by the body that damages body tissues (sepsis) (3 subjects, 9%).
Fourteen subjects (40%) had at least 1 AE reported by a study doctor as related to guadecitabine. These AEs were severe in 4 subjects (11%) or life threatening in 6 subjects (17%); none resulted in death. The AEs reported related to guadecitabine in at least 3 subjects were a low number of a type of blood cell important in fighting infections and a low number of this type of blood cell plus fever (each, 5 subjects, 14%), a low number of blood cells that help blood to clot (4 subjects, 11%), and lung infection (pneumonia) (3 subjects, 9%). In 7 subjects (20%), these AEs were considered serious, usually because they resulted in or lengthened hospitalization. These serious AEs reported in more than 1 subject were a low number of a type of blood cell important in fighting infections plus fever (5 subjects, 14%) and lung infection (pneumonia) (3 subjects, 9%).
No subjects had guadecitabine discontinued because of AEs, but 9 subjects (26%) had guadecitabine interrupted and 1 subject (3%) had the dose of guadecitabine reduced because of AEs. No subjects had guadecitabine discontinued or the dose of guadecitabine reduced because of an AE reported by a study doctor as related to guadecitabine, but 3 subjects (9%) had guadecitabine interrupted because of related AEs.
Within 30 days after last receiving quadecitabine, 1 subject (3%) died from worsening of the cancer (progressive disease). More than 30 days after last receiving quadecitabine, 8 subjects (23%) died. The 8 deaths were from worsening of the cancer (progressive disease, 3 subjects, 9%), AEs (3 subjects, 9%), or “Other” (2 subjects, 6%). None of the 3 fatal AEs (liver cancer and lung infections [pneumonia and viral pneumonia]) were reported by study doctors as related to guadecitabine.
No medically important or guadecitabine-related trends were seen in laboratory results other than those connected with low numbers of various types of blood cells, often seen in patients with blood cancers.
When Astex stopped this study 2583.0 days (about 7 years) from the dates subjects entered into the original studies, half of the subjects were alive and half the subjects were no longer alive.REC name
North West - Greater Manchester Central Research Ethics Committee
REC reference
20/NW/0135
Date of REC Opinion
17 Apr 2020
REC opinion
Further Information Favourable Opinion