Trial Information

Phase III 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

Objectives:

The primary objective of this study is to determine whether RICT leads to an improved
overall survival at three years 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

- Rate of complete and partial chimerism

- Safety and efficacy of donor lymphocyte infusions for relapse or minimal
residual disease.

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 or a transplant from an unrelated
donor.

- According to the investigator, fit for a RICT if a suitable sibling donor is found, and
also fit for further consolidation chemotherapy in case no suitable sibling donor is
found.

- At least one sibling willing to undergo HLA-typing

Procedures:

Patients will receive induction therapy according to institutional practice and will be
approached after achieving complete remission following one or two induction courses.
Patients without siblings or patients for whom a full-dose conditioned allogeneic
transplantation is planned will not be approached, neither will patients who are candidates
for an unrelated donor transplant or patients who are for 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, the sibling(s) will be briefly informed about the study
and asked if they are willing to undergo HLA-typing. Siblings with evident contraindications
to G-CSF or collection of peripheral blood stem cells should not proceed to HLA-typing.

- A patient's inclusion in the study is when blood sampling for tissue typing
(HLA-typing) of the first potential donor is made and an inclusion fax has been sent to
and approved by the national study office.

If found HLA-identical, the sibling will be asked to sign an informed consent to undergo
medical work-up and - if found fit for the procedures - G-CSF mobilization and harvest of
peripheral blood stem cells.

Included patients with a HLA-identical sibling 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, if deemed clinically
appropriate, 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 - 88 patients in the RICT group and 264
in the control group - 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.