Up-front Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia Patients Aged 65-75

Fondazione Policlinico Universitario Agostino Gemelli IRCCS19 enrolled

Overview

Patients with acute myeloid leukemia aged 65-75 have a very poor prognosis, irrespective of the treatment strategy, including demethylating agents or conventional chemotherapy. With these approaches, remission rates do not exceed 40%, and overall disease-free survival at 1 year is in the order of 15%. The hypothesis is that up-front allogeneic hematopoietic stem cell transplant will produce a complete remission rate of 60% on day +56-70, and disease-free survival at 1 year of 30%. This is a single arm phase II study of upfront allogeneic stem cell transplantation, for patients with acute myeloid leukemia aged 65-75: the primary endpoint is a complete remission rate on day +56-70. The secondary endpoint is a 1-year overall disease-free survival of 30%.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Myeloid Leukemia, Adult

Interventions

Patients classified as fit/unfit are included in the HSCT program. There are two early approaches allowed. A) Patients will be left untreated until HSCT B) Patients will receive 1 short course of chemotherapy before HSCT (Ara-C and anthracycline). Selection of strategy A or B, will be patient based on disease characteristics and dynamics or presence of high tumor load. Conditioning for haplo-HSCT should be started as soon as possible, within day 45 after initial diagnosis. This is to avoid delayed transplantation. Two dosing levels of the Thiotepa-Busulfan-Fludarabine (TBF) based protocol are allowed based on the clinical condition of the patient: fit patients below 70 will receive the TBF with 2 days of Busulfan, whereas patients with poorer clinical condition or above the age of 70 will receive a dose-reduced TBF, in which Busulfan may be reduced to 1 day only.

Eligibility

Sex: ALLMin age: 65 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients aged 65-75 * Patients with de novo or secondary acute myeloid leukemia (AML) - intermediate or high risk according to European LeukemiaNet (ELN) recommendations 2017 * Untreated patients at diagnosis of acute myeloid leukemia - patients may have received treatment for high-risk myelodysplastic syndromes with hypomethylating agents (HMA). They should not have received a course of induction chemotherapy to be eligible for this study * Haploidentical family stem cell donor or other suitable donors available * Fit and unfit patients by geriatric scale assessment * Signed informed consent. Exclusion Criteria: * Acute Myeloid Leukemia good risk according to European LeukemiaNet 2017 * Positive serology for Human Immunodeficiency Virus. * Serious organ dysfunction: left ventricular ejection fraction \< 40%, forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) \<50% of predicted, Liver Function Tests \> 5 x the upper limit of normal, or creatinine clearance \<30 ml/min . * Life expectancy less than 30 days. * Frail patients by geriatric scale assessment

Outcomes

Primary Outcomes

Rate of complete remission equal or higher than 60%

As a primary outcome measure, the rate of complete remission in treated patients will be evaluated. Complete remission will be assessed from days +56 to days +70 after transplant. A complete remission rate equal to or higher than 60% is expected.

Time frame: From day 56 to day +70 post-transplant