Reduced Intensity Conditioning Transplantation Versus Standard of Care in Acute Myeloid Leukemia
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Procedure: Reduced Intensity Conditioning Stem Cell Transplantation
- Registration Number
- NCT00342316
- Lead Sponsor
- Vastra Gotaland Region
- Brief Summary
This study compares overall survival between patients with acute myeloid leukemia, who are in complete remission following initial treatment with chemotherapy and whose remission is maintained either with a transplantation of stem cells obtained from a sibling or unrelated donor or with standard treatment, which is additional chemotherapy.
The study hypothesis is that the group transplanted with stem cells from a donor will have a superior survival compared with patients treated with standard of care.
- Detailed Description
Objectives:
The primary objective of this study is to determine whether RICT leads to an improved overall survival compared to conventional treatment for AML.
The secondary objectives of this study are to determine if:
* RICT leads to a superior long-term overall survival compared to conventional therapy.
* RICT leads to a superior disease-free survival compared to conventional therapy.
* Time to relapse is different between RICT and control groups.
* Quality of life is different between the two treatment groups.
* in RICT patients only:
* Safety and feasibility of the procedure
* Incidence and severity of acute and chronic Graft versus Host Disease (GvHD)
* Rate of complete and partial chimerism
Study Population:
* Newly diagnosed patients with de novo or secondary AML, intermediate or poor risk, in first complete remission aged 51-70 years.
* Not planned for a full-dose allogeneic transplant.
* According to the investigator, fit for a RICT if a suitable donor (sibling or unrelated) is found, and also fit for further consolidation chemotherapy in case no suitable donor is found.
Procedures:
Patients will receive induction therapy according to institutional practice and can be included after achieving complete remission. Patients for whom a full-dose conditioned allogeneic transplantation is planned will not be approached, neither will patients who are for other reasons judged to be ineligible for a RICT. Eligible patients will be informed about the study. After the patient's consent has been obtained, potential sibling donor(s) will be briefly informed about the study and asked if they are willing to undergo HLA-typing. Siblings with evident contraindications to granulocyte colony stimulating factor (G-CSF) or collection of peripheral blood stem cells should not proceed to HLA-typing. A search for an unrelated matched donor (MUD) will be initiated if there is no potential sibling donor, or if sibs are not HLA-identical or otherwise not fit for the donation procedure. A patient's inclusion in the study is when blood sampling for tissue typing (HLA-typing) of the first potential sibling donor is made, or when a search warrant for a MUD is dispatched.
* Note: To enable an early donor search, patients may be registered, but not included, for the study prior to CR. These patients will be included at date of achieved CR. Registered patients not achieving CR will not be included.
Included patients with a HLA-identical sibling or with an identified MUD will be assigned to the RICT group, and included patients without such a donor will automatically be in the control group. This is a HLA-based assignment, and the final intent-to-treat analysis will be based on the treatment assignment.
After treatment assignment, patients on the control arm should receive consolidation therapy as per institutional practice, whereas patients on the RICT arm may proceed directly to RICT or receive one or maximum two consolidation courses. Patients should be in complete remission at the time of transplant. All patients will be followed for relapse and survival for a period of at least three years.
The inclusion of 352 patients in complete remission provides a statistical power of 90 % to detect a difference in overall survival at three years of 20 percentage points, ie from 30 % of control patients to 50 % in RICT patients.
Inclusion was terminated 2016-07-19 after 360 registered patients. However, some pts were excluded due to grave protocol deviations or withdrawn consent. The data base was locked in June 2018 for analysis with 309 pts (after exclusions). Follow-up was \>2 yrs fo all pts.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 340
- Newly diagnosed patients with de novo or secondary AML
- Intermediate or poor risk
- In first complete remission
- Age 51-70 years
- Fit for the procedure
- Fit for further consolidation chemotherapy
- Planned for a full-dose allogeneic transplant
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Stem cell transplant (RICT) Reduced Intensity Conditioning Stem Cell Transplantation Receiving intervention consisting of Reduced Intensity Conditioning Stem Cell Transplantation
- Primary Outcome Measures
Name Time Method Overall survival (OS) From Inclusion until one of the above events (≥2yrs in all surviving pts). OS is the time from Inclusion to death, lost to follow-up, refusal, or study termination.
- Secondary Outcome Measures
Name Time Method Non-relapse mortality (NRM). Numbers and causes of death in non-relapsed pts From Inclusion to relapse or death until study termination. NRM is death without preceding relapse, from Inclusion to study termination.
Disease-free survival From Inclusion to relapse, death or study termination. Follow-up ≥24 mo in all surviving pts. DFS is the time from Inclusion until date of first documented relapse, death from any cause whichever came first, assessed until study termination.
Quality of Life for pts in the RICT and Control Groups. All pts were asked to fill out the instrument at 12 and 24 months after inclusion European Organization for Research and Treatment of Cancer (EORTC). Quality of Life Questionnaire (QLQ), Cancer C) #30. An instrument commonly used for the evaluation of QoL after under and after cancer treatment
Acute and Chronic Graft-versus-Host Disease (GvHD) Acute GvHD: From transplant to 3 months. Chronic From transplantation to relapse, death or study termination In transplanted pts only. Acute GvHD appears from transplant to 100 days. Chronic GvHD occurs later, and often remains for years. Both are clinical diagnoses and cGvHD grading were performed annually until death or study termination.
Trial Locations
- Locations (25)
Dept of Hematology, University Hospital
🇩🇪Freiburg, Germany
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Cancer Care Manitoba
🇨🇦Winnipeg, Manitoba, Canada
McMaster Site Ward 3Z, Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Hematology, Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Hématologie, Maisonneuve-Rosemont Hospital
🇨🇦Montreal, Quebec, Canada
Hematology, Royal Victoria Hospital
🇨🇦Montreal, Quebec, Canada
L'Hôtel Dieu de Quebec
🇨🇦Quebec City, Quebec, Canada
Hématologie, Hospital CHA Enfant-Jésus
🇨🇦Quebec City, Quebec, Canada
Wellington Hospital
🇳🇿Wellington, New Zealand
Department of Hematology, Sahlgrenska University Hospital
🇸🇪Goteborg, Sweden
Sunderby Hospital
🇸🇪Luleå, Sweden
Skåne University Hospital Lund
🇸🇪Lund, Sweden
Karolinska University Hospital Huddinge
🇸🇪Stockholm, Sweden
Karolinska University Hospital Solna
🇸🇪Stockholm, Sweden
University Hospital Örebro
🇸🇪Örebro, Sweden
Uppsala Akademiska Hospital
🇸🇪Uppsala, Sweden
Turku University Hospital
🇫🇮Turku, Finland
University Hospital of Patras
🇬🇷Patras, Greece
Section of Hematology, National Hospital
🇳🇴Oslo, Norway
Austalasian Leukaemia &Lymphoma Group Limited
🇦🇺East Melbourne, Victoria, Australia
Tartu University Hospital
🇪🇪Tartu, Estonia
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia