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

NCT03902665 | Completed Phase 2

• 1 other identifier: 1749
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Allogeneic hematopoietic stem cell transplantation

EXPERIMENTAL

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)

Interventions

Up-front allogeneic hematopoietic stem cell transplantation (HSCT) 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.

Also known as: HSCT

Allogeneic hematopoietic stem cell transplantation

Eligibility Criteria

• Age: 65 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead
• Associazione Italiana per la Ricerca sul Cancro: collaborator

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, RM, 00168, Italy

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Andrea Bacigalupo, Prof.

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 2, 2019
• First Posted: April 4, 2019
• Study Start: March 15, 2019
• Primary Completion: March 31, 2024
• Study Completion: June 30, 2024
• Last Updated: July 23, 2024

Record last verified: 2024-07

Locations

IT (1)