Acute Myeloid LeukemiaNCT00342316
Reduced Intensity Conditioning Transplantation Versus Standard of Care in Acute Myeloid Leukemia
A study testing Reduced Intensity Conditioning Stem Cell Transplantation in people with Acute Myeloid Leukemia, run by Vastra Gotaland Region at 25 sites in 9 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 51 to 70 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Reduced Intensity Conditioning Stem Cell Transplantation
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 340 participants
- Where
- 25 sitesin 9 countries
- Study dates
- 18 Dec 2003to 20 Jul 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 51 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Planned for a full-dose allogeneic transplant
Trial locations and contacts
25 sites in 9 countries.
25 sites in 9 countries
Canada8 sites
McMaster Site Ward 3Z, Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5
Hématologie, Maisonneuve-Rosemont Hospital
Montreal, Quebec, H1T 2M4
Hematology, Royal Victoria Hospital
Montreal, Quebec, H3A 1A1
Hematology, Ottawa Hospital
Ottawa, Ontario, K1H 8L6
Hématologie, Hospital CHA Enfant-Jésus
Québec, Quebec, G1J 1Z4
L'Hôtel Dieu de Quebec
Québec, Quebec
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
Cancer Care Manitoba
Winnipeg, Manitoba, R3E 0V9
Sweden7 sites
Department of Hematology, Sahlgrenska University Hospital
Gothenburg, 41345
Sunderby Hospital
Luleå
Skåne University Hospital Lund
Lund
University Hospital Örebro
Örebro
Karolinska University Hospital Huddinge
Stockholm
Karolinska University Hospital Solna
Stockholm
Uppsala Akademiska Hospital
Uppsala
Australia3 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Austalasian Leukaemia &Lymphoma Group Limited
East Melbourne, Victoria, 3002
New Zealand2 sites
Christchurch Hospital
Christchurch
Wellington Hospital
Wellington, 6021
Germany1 site
Dept of Hematology, University Hospital
Freiburg im Breisgau, 79106
About this study
Official title: Prospective Controlled Clinical Study of Allogeneic Stem Cell Transplantation With Reduced Conditioning (RICT) Versus Best Standard of Care in Acute Myeloid Leukemia (AML)in First Complete Remission (CR)
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.
Read the 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.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Reduced Intensity Conditioning Stem Cell Transplantation
- Keywords
- Acute Myeloid Leukemia, Stem Cell Transplantation, Reduced Intensity Conditioning, Survival, Relapse
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reduced Intensity Conditioning Stem Cell TransplantationProcedure or surgery
One of the following conditioning regimens:
- Busulphan (orally or IV), fludarabine
- Fludarabine, carmustine, melfalan
- Cyclophosphamide, fludarabine
| Study group | Role | What they receive |
|---|---|---|
| Stem cell transplant (RICT) | Experimental | Receiving intervention consisting of Reduced Intensity Conditioning Stem Cell Transplantation Receives: Procedure: Reduced Intensity Conditioning Stem Cell Transplantation |
| Control arm | No intervention | Treatment according to standard of care, i.e. not undergoing RICT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
OS is the time from Inclusion to death, lost to follow-up, refusal, or study termination.
Measured: From Inclusion until one of the above events (≥2yrs in all surviving pts).
Secondary outcomes (4)
Disease-free survival
DFS is the time from Inclusion until date of first documented relapse, death from any cause whichever came first, assessed until study termination.
Measured: From Inclusion to relapse, death or study termination. Follow-up ≥24 mo in all surviving pts.
Quality of Life for pts in the RICT and Control Groups.
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
Measured: All pts were asked to fill out the instrument at 12 and 24 months after inclusion
Non-relapse mortality (NRM). Numbers and causes of death in non-relapsed pts
NRM is death without preceding relapse, from Inclusion to study termination.
Measured: From Inclusion to relapse or death until study termination.
Acute and Chronic Graft-versus-Host Disease (GvHD)
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.
Measured: Acute GvHD: From transplant to 3 months. Chronic From transplantation to relapse, death or study termination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2006 (estimated)
- Study start18 Dec 2003
- Primary completion5 Jul 2018
- Study completion20 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Vastra Gotaland RegionThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Formally, this is not Phase III study, since there are no new drugs or interventions. Rather - a prospective, controlled study where we include pts aimed for alloSCT before any donor search. Both groups of pts (with or without a matched donor) are followed ≥2yrs. The hypothesis is that pts with a donor do better than those without a donor (sib and/or unrelated).
- Masking
- None (open label)
- Enrolment
- 340 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vastra Gotaland Region
- Sponsor type
- Other government
- Collaborators
- The Canadian Blood and Marrow Transplant Group, Australasian Leukaemia and Lymphoma Group
- Responsible party
- Sponsor
- Investigators
- Mats Brune, MD, PhD, Principal investigator, Göteborg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00342316
- Sponsor's protocol ID
- TRALG1/02
- Status last verified
- Jan 2020
- First submitted
- 20 Jun 2006
- Last updated
- 27 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Controlled Clinical Study of Allogeneic Stem Cell Transplantation With Reduced Conditioning (RICT) Versus Best Standard of Care in Acute Myeloid Leukemia (AML)in First Complete Remission (CR)
- ClinicalTrials.gov ID
- NCT00342316
- Acronym / sponsor ID
- TRALG1/02
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Acute Myeloid Leukemia, Stem Cell Transplantation, Reduced Intensity Conditioning, Survival, Relapse
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 340 participants (actual)
- Lead sponsor
- Vastra Gotaland RegionOther government
- Collaborators
- The Canadian Blood and Marrow Transplant Group, Australasian Leukaemia and Lymphoma Group
- Study start
- 18 Dec 2003
- Primary completion
- 5 Jul 2018 (actual)
- Study completion
- 20 Jul 2018 (actual)
- First posted
- 21 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Formally, this is not Phase III study, since there are no new drugs or interventions. Rather - a prospective, controlled study where we include pts aimed for alloSCT before any donor search. Both groups of pts (with or without a matched donor) are followed ≥2yrs. The hypothesis is that pts with a donor do better than those without a donor (sib and/or unrelated).
| Arm | Type | Receives |
|---|---|---|
| Stem cell transplant (RICT) | Experimental | Procedure: Reduced Intensity Conditioning Stem Cell TransplantationReceiving intervention consisting of Reduced Intensity Conditioning Stem Cell Transplantation |
| Control arm | No intervention | –Treatment according to standard of care, i.e. not undergoing RICT |
Who may qualify
- Ages
- 51 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (1 listed)
- Planned for a full-dose allogeneic transplant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Reduced Intensity Conditioning Stem Cell TransplantationOne of the following conditioning regimens: 1. Busulphan (orally or IV), fludarabine 2. Fludarabine, carmustine, melfalan 3. Cyclophosphamide, fludarabine | Procedure or surgery | Stem cell transplant (RICT) |
Primary outcome
Overall survival (OS)
Time frame: 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.
4 secondary outcomes
Disease-free survival
Time frame: From Inclusion to relapse, death or study termination. Follow-up ≥24 mo in all surviving pts.
Quality of Life for pts in the RICT and Control Groups.
Time frame: All pts were asked to fill out the instrument at 12 and 24 months after inclusion
Non-relapse mortality (NRM). Numbers and causes of death in non-relapsed pts
Time frame: From Inclusion to relapse or death until study termination.
Acute and Chronic Graft-versus-Host Disease (GvHD)
Time frame: Acute GvHD: From transplant to 3 months. Chronic From transplantation to relapse, death or study termination
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mats Brune, MD, PhD principal investigator
Göteborg University
25 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Reduced Intensity Conditioning Stem Cell Transplantation in people with Acute Myeloid Leukemia, run by Vastra Gotaland Region at 25 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in Canada, Sweden, Australia, New Zealand, Estonia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (OS) (time frame: From Inclusion until one of the above events (≥2yrs in all surviving pts).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.