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

Acute Myeloid Leukemia, Adult Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03902665
• Other study ID #: UBA17
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: March 15, 2019
• Est. completion date: March 30, 2021

Study information

• Verified date: April 2019
• Source: Policlinico Universitario Agostino Gemelli
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 3
• Est. completion date: March 30, 2021
• Est. primary completion date: March 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia, Adult
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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.

Locations

Country	Name	City	State
Italy	Fondazione Policlinico Universitario A. Gemelli IRCCS	Roma	RM

Sponsors (2)

Lead Sponsor	Collaborator
Policlinico Universitario Agostino Gemelli	Associazione Italiana per la Ricerca sul Cancro

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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