CR-AIR-009
Research type
Research Study
Full title
A Phase III, multicenter, randomised controlled study to compare safety and efficacy of a haploidentical HSCT and adjunctive treatment with ATIR101, a T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells, versus a haploidentical HSCT with post-transplant cyclophosphamide in patients with a hematologic malignancy (HATCY study)
IRAS ID
225522
Contact name
Annelies Legters
Contact email
Sponsor organisation
Kiadis Pharma Netherlands BV
Eudract number
2016-004672-21
Clinicaltrials.gov Identifier
Duration of Study in the UK
4 years, 5 months, 0 days
Research summary
Research Summary \nThere are no curative therapies for blood cancer apart from a blood stem cell transplantation. A major complication for blood stem cell transplantations is graft-versus-host-disease (GVHD). To reduce the risk of GVHD, it is best to have a fully matching donor. However, this is often not possible. An alternative is to use a family donor whose cells only partially match (haploidentical donor). \n\nThis study will compare the safety and efficacy of two methods to perform haploidentical blood stem cell transplantations (HSCT). The methods are referred to as ‘post-transplantation cyclophosphamide (PTCy)’ and ‘ATIR101’. Patients will be randomly assigned to the PTCy or the ATIR101 method. \n\nPTCy: After the HSCT, part of the mature donor immune cells will get activated as they recognise the patients’ body as foreign (GVHD causing cells). A high dose of cyclophosphamide is given on day 3 and day 4 or 5 to kill these activated mature donor immune cells, leaving the rest of the donor cells alive. Immune suppressive agents are given for approximately 6 months to prevent further GVHD from happening.\n\nATIR101: Mature donor immune cells are removed as much as possible from the HSCT before it is given. The patient will not receive immune suppressive agents. To help fight against infections, the patient will receive an infusion of mature donor immune cells from which the GVHD causing cells have been removed (ATIR101). In order to produce ATIR101, white blood cells from patient and donor are collected prior to the blood stem cell transplantation and these are treated in a specialised manufacturing facility. \n\nAfter the HSCT, weekly assessments will be performed for the first 10 weeks, then monthly until 6 months, every 2 months until month 12 and every 3 months until month 24. In total, approximately 195 patients in Europe and North-America will participate.\n\nSummary of Results\n\nATIR101 and post-transplantation cyclophosphamide:\nOn 29 November 2017, the pharmaceutical company Kiadis Pharma Netherlands B.V. initiated a phase III clinical study (phase III clinical studies compare a new treatment with the best currently available treatment, the so-called standard treatment). The phase III clinical study was initiated to compare the safety and effectiveness of a new therapy called “ATIR101” with the standard treatment of cyclophosphamide (PTCy) given after a specific type of stem cell transplantation (haploidentical) in patients with certain types of blood cancers. A haploidentical stem cell transplantation is a procedure during which a patient’s unhealthy blood-forming cells are replaced with healthy cells from a related donor (from a sibling, a parent, or child), but not “matched” donor (where the donor cells are completely matched to the patient’s cells). Patients participating in this study had previously responded to chemotherapy and irradiation treatments to achieve complete remission (when tests, physical exams, and scans show that all signs of cancer are gone), though were at high risk of having their blood cancer came back. Participants in the study were randomly assigned (like flipping a coin) to receive either the new therapy, ATIR101, or standard treatment of PTCy following their stem cell transplantation procedure. \n\nATIR101:\nATIR101 is a medicine developed with the aim to improve survival in patients with blood cancers being treated with a haploidentical stem cell transplantation. ATIR101 was given to these patients after a stem cell transplantation procedure with stem cells from which certain cells (T-cells) were removed (depleted). \n\nT-cells are a type of white blood cell and a powerful part of the immune system. During a stem cell transplantation with a non-matched donor, T-cells may identify the new healthy cells as “foreign” and attack the patient’s tissues. This action by the T-cells can cause a serious side-effect called graft-versus-host disease (GVHD). Removing T-cells from the healthy donor stem cells before giving them to the patient reduces the risk of GVHD, but also makes it harder for the transplantation recipient to rebuild their immune system to fight against infections and recurrence of the cancer cells. \n\nATIR101 was made specific for each patient, and contained the donor’s healthy T-cells, that were selectively treated to remove just those cells that might attack the patient’s tissue and cause GVHD. ATIR101 cells were then given after the transplantation procedure to replace the missing T-cells in the transplanted patient to help fight infections and fight cancer cells.\n\nPTCy:\nPost-transplantation cyclophosphamide (PTCy) is considered a standard treatment administered to patients undergoing stem cell transplantation to prevent transplantation rejection and GVHD. \n\nBased on results of earlier studies using ATIR101, this clinical study was aimed to test the effect of using ATIR101 as a promising treatment alternative to the standard use of PTCy to improve transplantation outcomes.\n\nStudy CR-AIR-009\nThis study was planned to enroll a total of 250 patients, who were randomly assigned to receive either a stem cell transplantation (from which T-cells have been removed) followed by ATIR101 infusion (given by dripping into a vein), or a stem cell transplantation (containing T-cells) followed by a high dose of PTCy. Both men and women 18-70 years old were invited to participate in the clinical study. Participants in the study were followed for 2 years after the stem cell transplantation. \n\nSeveral cancer centers around the world participated in this study, including centers in Belgium, Canada, Croatia, the Netherlands, Portugal, Spain, the United Kingdom, and the United States. \n\nThe study was coordinated by Prof. Denis Claude Roy, MD from the Research Center and Cellular Therapy Laboratory at the Maisonneuve-Rosemont Hospital (Montreal, Canada) and Prof. Stephan Mielke, MD from the Centre for Allogeneic Stem Cell Transplantation at Karolinska University Hospital (Stockholm, Sweden).\n\nSummary of study results CR-AIR-009:\nThe aim of this study was to see if using ATIR101 after stem cell transplant was better than (superior to) the standard treatment using PTCy. This was measured by monitoring the time a patient lived without any signs of GVHD or symptoms of blood cancer (called GVHD-free/relapse free survival) for patients treated with ATIR101 when compared to patients treated with PTCy. The results of the study show that ATIR101 did not show better results than PTCy for GVHD-free/relapse free survival in these patients. \n\nIn the ATIR101 group of patients, there was a higher-than-expected percentage of patients who stopped participation in the study earlier than planned and before they received ATIR101 treatment. This was mainly due to the time needed to make the personalized medication (a medication specifically made for the patients from his/her donor’s cells), and the patient’s opted to leave the study to have other treatments. Together with more favorable data on GVHD-free/relapse free survival for treatment with PTCy, enrollment into the study was stopped earlier than planned on 12 November 2019.\n\nThe information collected from all patients enrolled in the study until the study was stopped on 12 November 2019 (referred to as the “active study phase”) showed that there were no unexpected side-effects in patients who received ATIR101. Serious side-effects in patients treated in both groups were side effects usually seen in patients undergoing stem cell transplantation. \n\nLong term follow-up results CR-AIR-009:\nAfter enrollment into the study was stopped, on 12 November 2019, all patients who received treatment with ATIR101 or PTCy, and who were still in the study, were followed for 2 years from their transplant date for the collection of information about any serious side-effects, occurrence of GVHD and survival. \n\nThe results confirm the findings collected during the “active study phase,” and showed that patients treated with ATIR101 had no better results for GVHD-free/relapse free survival when compared to patients who received treatment with PTCy. \n\nThe 2-year follow-up safety information (safety data) did not show any safety concerns and are consistent with the safety information collected during the “active study phase.” \n
REC name
South Central - Oxford A Research Ethics Committee
REC reference
17/SC/0554
Date of REC Opinion
18 Jan 2018
REC opinion
Further Information Favourable Opinion