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

Vastra Gotaland Region

Status: Completed

Conditions: Acute Myeloid Leukemia

Treatments: Procedure: Reduced Intensity Conditioning Stem Cell Transplantation

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT00342316

TRALG1/02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 340 patients

Sex: All

Ages: 51 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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340 participants in 2 patient groups

Stem cell transplant (RICT)

Experimental group

Description:

Receiving intervention consisting of Reduced Intensity Conditioning Stem Cell Transplantation

Treatment:

Procedure: Reduced Intensity Conditioning Stem Cell Transplantation

Control arm

No Intervention group

Description:

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