Reduced Intensity Conditioning Transplantation Versus Standard of Care in Acute Myeloid Leukemia

NCT ID: NCT00342316

Last Updated: 2020-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 340 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-12-18
• Study Completion Date: 2018-07-20

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stem cell transplant (RICT)

Receiving intervention consisting of Reduced Intensity Conditioning Stem Cell Transplantation

Group Type: EXPERIMENTAL

Reduced Intensity Conditioning Stem Cell Transplantation

Intervention Type: PROCEDURE

One of the following conditioning regimens:

1. Busulphan (orally or IV), fludarabine

2. Fludarabine, carmustine, melfalan

3. Cyclophosphamide, fludarabine

Control arm

Treatment according to standard of care, i.e. not undergoing RICT

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Reduced Intensity Conditioning Stem Cell Transplantation

One of the following conditioning regimens:

1. Busulphan (orally or IV), fludarabine

2. Fludarabine, carmustine, melfalan

3. Cyclophosphamide, fludarabine

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 51 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Canadian Blood and Marrow Transplant Group

NETWORK

Sponsor Role: collaborator

Australasian Leukaemia and Lymphoma Group

OTHER

Sponsor Role: collaborator

Vastra Gotaland Region

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mats Brune, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Göteborg University

Locations

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Austalasian Leukaemia &Lymphoma Group Limited

East Melbourne, Victoria, Australia

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

Hématologie, Hospital CHA Enfant-Jésus

Québec, Quebec, Canada

L'Hôtel Dieu de Quebec

Québec, Quebec, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Tartu University Hospital

Tartu, , Estonia

Turku University Hospital

Turku, , Finland

Dept of Hematology, University Hospital

Freiburg im Breisgau, , Germany

University Hospital of Patras

Pátrai, , Greece

Christchurch Hospital

Christchurch, , New Zealand

Wellington Hospital

Wellington, , New Zealand

Section of Hematology, National Hospital

Oslo, , Norway

Department of Hematology, Sahlgrenska University Hospital

Gothenburg, , Sweden

Sunderby Hospital

Luleå, , Sweden

Skåne University Hospital Lund

Lund, , Sweden

University Hospital Örebro

Örebro, , Sweden

Karolinska University Hospital Huddinge

Stockholm, , Sweden

Karolinska University Hospital Solna

Stockholm, , Sweden

Uppsala Akademiska Hospital

Uppsala, , Sweden

Countries

Australia; Canada; Estonia; Finland; Germany; Greece; New Zealand; Norway; Sweden

Other Identifiers

TRALG1/02

Identifier Type: -

Identifier Source: org_study_id