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

Study Overview
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Brief Summary
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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%.

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

Conditions
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Acute Myeloid Leukemia, Adult

Intervention / Treatment
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* Drug: Up-front allogeneic hematopoietic stem cell transplantation (HSCT)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogeneic hematopoietic stem cell transplantation<br>Day -6, -5 Thiotepa 5 mg/kg/day . Day -4 to -3 Busulfan i. v 3,2 mg/kg/day and fludarabine i.v. 50 mg/m2 /day Day -2 fludarabine i.v. 50 mg/m2 Day -1 Rest Day 0 Begin cyclosporine; Infusion of T cell replete bone marrow transplant Day 1 Begin mycophenolate mofetil Day 3 and 5 Cyclophosphamide 50 mg/kg IV and Mesna Day 6 G-colony stimulating factor | Drug: Up-front allogeneic hematopoietic stem cell transplantation (HSCT)<br>* 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.<br>* Other names: HSCT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From day 56 to day +70 post-transplant |