Clinical trial NCT00342316: Reduced Intensity Conditioning Transplantation Versus Standard of Care in Acute Myeloid Leukemia
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia
Stem Cell Transplantation
Reduced Intensity Conditioning
Survival
Relapse
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: The Canadian Blood and Marrow Transplant Group
name: Australasian Leukaemia and Lymphoma Group
First posted: 2006-06-21
Enrollment: 340
Sex: ALL
Minimum age (years): 51
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* Planned for a full-dose allogeneic transplant

Primary outcomes:
measure: Overall survival (OS)
timeFrame: From Inclusion until one of the above events (≥2yrs in all surviving pts).
Secondary outcomes:
measure: Disease-free survival
timeFrame: From Inclusion to relapse, death or study termination. Follow-up ≥24 mo in all surviving pts.
measure: Quality of Life for pts in the RICT and Control Groups.
timeFrame: All pts were asked to fill out the instrument at 12 and 24 months after inclusion
measure: Non-relapse mortality (NRM). Numbers and causes of death in non-relapsed pts
timeFrame: From Inclusion to relapse or death until study termination.
measure: Acute and Chronic Graft-versus-Host Disease (GvHD)
timeFrame: Acute GvHD: From transplant to 3 months. Chronic From transplantation to relapse, death or study termination
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: East Melbourne
country: Australia
facility: Austalasian Leukaemia &Lymphoma Group Limited
state: Victoria
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: Hamilton
country: Canada
facility: McMaster Site Ward 3Z, Hamilton Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: Hematology, Ottawa Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hématologie, Maisonneuve-Rosemont Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hematology, Royal Victoria Hospital
state: Quebec
city: Quebec City
country: Canada
facility: Hématologie, Hospital CHA Enfant-Jésus
state: Quebec
city: Quebec City
country: Canada
facility: L'Hôtel Dieu de Quebec
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Freiburg
country: Germany
facility: Dept of Hematology, University Hospital
city: Patras
country: Greece
facility: University Hospital of Patras
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Oslo
country: Norway
facility: Section of Hematology, National Hospital
city: Goteborg
country: Sweden
facility: Department of Hematology, Sahlgrenska University Hospital
city: Luleå
country: Sweden
facility: Sunderby Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital Lund
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Huddinge
city: Stockholm
country: Sweden
facility: Karolinska University Hospital Solna
city: Uppsala
country: Sweden
facility: Uppsala Akademiska Hospital
city: Örebro
country: Sweden
facility: University Hospital Örebro
Study officials:
affiliation: Göteborg University
name: Mats Brune, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: