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

NCT ID: NCT03902665

Last Updated: 2024-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-15
• Study Completion Date: 2024-06-30

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%.

Conditions

Acute Myeloid Leukemia, Adult

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Up-front allogeneic hematopoietic stem cell transplantation (HSCT)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

HSCT

Eligibility Criteria

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

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Associazione Italiana per la Ricerca sul Cancro

OTHER

Sponsor Role: collaborator

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

BACIGALUPO ANDREA

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrea Bacigalupo, Prof.

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Universitario A. Gemelli, IRCCS

Locations

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, RM, Italy

Countries

Italy

Other Identifiers

1749

Identifier Type: -

Identifier Source: org_study_id