Up-front Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia Patients Aged 65-75
Study Details
Study Description
Brief Summary
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%.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Allogeneic hematopoietic stem cell transplantation 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)
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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Rate of complete remission equal or higher than 60% [From day 56 to day +70 post-transplant]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients aged 65-75
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Patients with de novo or secondary acute myeloid leukemia (AML) - intermediate or high risk according to European LeukemiaNet (ELN) recommendations 2017
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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
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Haploidentical family stem cell donor or other suitable donors available
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Fit and unfit patients by geriatric scale assessment
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Signed informed consent.
Exclusion Criteria:
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Acute Myeloid Leukemia good risk according to European LeukemiaNet 2017
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Positive serology for Human Immunodeficiency Virus.
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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 .
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Life expectancy less than 30 days.
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Frail patients by geriatric scale assessment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fondazione Policlinico Universitario A. Gemelli IRCCS | Roma | RM | Italy | 00168 |
Sponsors and Collaborators
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Associazione Italiana per la Ricerca sul Cancro
Investigators
- Principal Investigator: Andrea Bacigalupo, Prof., Fondazione Policlinico Universitario A. Gemelli, IRCCS
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UBA17