A Study Comparing Allogeneic Hematopoietic Cell Transplantation Versus Best Available Standard of Care Therapy in Elderly Patients With Acute Myeloid Leukemia (ALLO-BEST)

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ClinicalTrials.gov Identifier: NCT04822766

Recruitment Status : Recruiting

First Posted : March 30, 2021

Last Update Posted : January 25, 2022

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Sponsor:

Information provided by (Responsible Party):

Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

A subject of major interest for researchers, clinicians, patients, and payers, is the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of these older patients with AML. With conventional induction chemotherapy or hypomethylating agents, the expected 2-year overall survival (OS) is less than 25% in patients with intermediate- or high-risk disease. The 2-year OS ranges from 50 to 56% with allo-HSCT in AML patients older than 65 years.

With a phase III comparative, randomized, controlled, prospective, multicenter study, the trial aim to assess prospectively the outcomes and quality of life of older patients with AML receiving allo-HSCT strategy compared to those receiving a non-transplant approach.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia	Procedure: Hematopoietic stem cell transplantation Drug: Best chemotherapy treatment	Not Applicable

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Detailed Description:

Every year, 30,000 patients in Europe and 20,000 in the USA are diagnosed with acute myeloid leukemia (AML). More than half of them are over 65 years old. In this older population, the median overall survival (OS) is only 2 to 8 months. With conventional induction chemotherapy or hypomethylating agents, the expected 2-year OS is less than 25% in patients with intermediate- or high-risk disease.

Performing an allo-HSCT in older patients is however still controversial because of the higher risk of non-relapse mortality (15 to 35%) and graft-versus-host disease. Depending on the center policy, patients older than 65 years will either be contraindicated for transplant or will receive allo-HSCT. Noteworthy, no prospective randomized trial has yet compared allo-HSCT to a non-transplant strategy in older patients with AML. A previous attempt made 10 years ago, by the EBMT to run a slightly similar trial, has failed in France and most European countries, mainly (i) because it mandated the type of transplant procedure to be applied and (ii) because of the absence of novel and effective drugs.

Every year, 30,000 patients in Europe and 20,000 in the USA are diagnosed with acute myeloid leukemia (AML). More than half of them are over 65 years old. In this older population, the median overall survival (OS) is only 2 to 8 months. With conventional induction chemotherapy or hypometylating agents, the expected 2-year OS is less than 25% in patients with intermediate- or high-risk disease.

New targeted therapies and treatment strategies are evolving rapidly. A standardized unique treatment administrated to all sub-types of AML is no longer the optimal approach for induction and non-transplant maintenance strategies. No treatment has reached consensus for older patients. For these reasons, this trial will not limit the choices of drugs administered to the patients but compare two strategies allowing patients to receive the best available standard of care.

The trial aim to assess prospectively the outcomes and quality of life of older patients with AML receiving allo-HSCT strategy compared to those receiving a non-transplant approach.

Patients will receive initial treatment with chemotherapy (or other appropriate non-palliative therapy). Once first complete remission is achieved and a donor is identified, patients will be included.

Patients will be randomly assigned (1:1) after inclusion to receive one of the following strategy:

Allogeneic hematopoietic stem cell transplantation arm: patients will undergo allo-HSCT after consolidation therapy (or completion of other appropriate non-palliative strategy) according to standard procedures of the transplant center (choice of donor, conditioning regimen, GVHD and infection prophylaxis). The use of novel therapies (such as sorafenib, midaustorine, venetoclax, etc.) will be allowed as post-transplantation maintenance strategy
Non-transplant arm: patients will be treated according to the standard procedures of the treating center for this type of population.

All patients will receive the best available treatments (including additional conventional chemotherapy or other non-palliative therapies such as 5-azacytidine, decitabine, venetoclax, midaustorine, enasidenib, etc.). Supportive care will be performed according to each participating center usual practice.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	172 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Allogeneic Hematopoietic Cell Transplantation Versus Best Available Standard of Care Therapy in Elderly Patients With Acute Myeloid Leukemia: a Randomized Phase 3 Trial
Actual Study Start Date :	December 31, 2021
Estimated Primary Completion Date :	January 2024
Estimated Study Completion Date :	January 2024

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Familial acute myeloid leukemia with mutated CEBPA Cytogenetically normal acute myeloid leukemia Core binding factor acute myeloid leukemia

MedlinePlus related topics: Acute Myeloid Leukemia Leukemia

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Chemotherapy	Drug: Best chemotherapy treatment patients will be treated according to the standard procedures of the treating center for this type of population. Patients will receive the best available treatments (including additional conventional chemotherapy or other non-palliative therapies such as 5-azacytidine, decitabine, venetoclax, midaustorine, enasidenib, etc.).
Experimental: Allogeneic Hematopoietic Cell Transplantation Time of transplant procedure The best available treatments of AML	Procedure: Hematopoietic stem cell transplantation patients will undergo allo-HSCT after consolidation therapy (or completion of other appropriate non-palliative strategy) according to standard procedures of the transplant center (choice of donor, conditioning regimen, GVHD and infection prophylaxis). The use of novel therapies (such as sorafenib, midaustorine, venetoclax, etc.) will be allowed as post-transplantation maintenance strategy.

Arm

Intervention/treatment

Active Comparator: Chemotherapy

Drug: Best chemotherapy treatment

patients will be treated according to the standard procedures of the treating center for this type of population. Patients will receive the best available treatments (including additional conventional chemotherapy or other non-palliative therapies such as 5-azacytidine, decitabine, venetoclax, midaustorine, enasidenib, etc.).

Experimental: Allogeneic Hematopoietic Cell Transplantation

Time of transplant procedure The best available treatments of AML

Procedure: Hematopoietic stem cell transplantation

patients will undergo allo-HSCT after consolidation therapy (or completion of other appropriate non-palliative strategy) according to standard procedures of the transplant center (choice of donor, conditioning regimen, GVHD and infection prophylaxis). The use of novel therapies (such as sorafenib, midaustorine, venetoclax, etc.) will be allowed as post-transplantation maintenance strategy.

Outcome Measures

Primary Outcome Measures :

Overall survival [ Time Frame: 2 years after the inclusion ]
From inclusion (time of identification of potential donor) until death or at 24 months, whichever comes first]

Secondary Outcome Measures :

Leukemia free survival [ Time Frame: within the 2 years after inclusion ]
from inclusion (time of identification of potential donor) until relapse and/or death from any cause or at 24 months, whichever comes first
Assessment of MRD and time to relapse from inclusion up to 2 years [ Time Frame: : time between inclusion and date of relapse or at 24 months, whichever comes first] ]
Quality of life FACT-BMT [ Time Frame: at baseline, 12 and 24 months after inclusion ]
FACT-BMT (Functional Assessment of Cancer Therapy - Bone Marrow Transplant)
Quality of life EQ 5D 5L [ Time Frame: at baseline, 12 and 24 months after inclusion ]
EQ 5D 5L (EuroQol group)
The Incremental cost-effectiveness ratios (ICERs) expressed in cost per quality-adjusted life-year (QALY) gained [ Time Frame: 2 years after inclusion ]
from inclusion (time of identification of potential donor) until death from any cause or at 24 months, whichever comes first
The Incremental cost-effectiveness ratios (ICERs) expressed in cost per Life Year Gained [ Time Frame: 2 years after inclusion ]
from inclusion (time of identification of potential donor) until death from any cause or at 24 months, whichever comes first
Non-relapse mortality [ Time Frame: within the 2 years after inclusion ]
from inclusion (time of identification of potential donor) until death without evidence of relapse or at 24 months, whichever comes first
In allo-HSCT patients only: cumulative incidence of acute and chronic graft-versus-host disease (GVHD) [ Time Frame: within the 2 years after inclusion ]
from transplantation until occurrence of GVHD or death from any cause or at 24 months after inclusion, whichever comes first
In allo-HSCT patients only: severity of acute and chronic graft-versus-host disease (GVHD) [ Time Frame: within the 2 years after inclusion ]
from transplantation until occurrence of GVHD or death from any cause or at 24 months after inclusion, whichever comes first

Eligibility Criteria

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Ages Eligible for Study:	65 Years to 75 Years (Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Men and women
Age ≥ 65 and ≤ 75 years
Newly diagnosed patients with de novo or secondary AML in first complete remission who are considered as potential candidates and eligible for an allo-HSCT procedure
Presence of a donor (matched related or unrelated or haplo-mismatched) willing to donate peripheral blood stem cells
Patient is fit for the allo-HSCT procedure
Patient is fit for further consolidation therapy (non-transplant arm)
Written informed consent

Exclusion Criteria:

Acute promyelocytic leukemia (AML FAB M3)
AML deemed not eligible for allo-HSCT
Karnofsky score <70%
HIV positive patient
Life expectancy less than one month according to the attending physician
Acute or chronic heart failure (Cardiac ejection fraction < 40%)
Pulmonary function - diffusion capacity < 50% predicted
Estimated glomerular filtration rate < 50 ml/min (CKD-EPI)
Severe neurological disorders
Patient subject to a legal protection measure (guardianship, curatorship and safeguard of justice) or unable to consent
Patient deprived of their liberty by a judicial or administrative decision
Patient with severe psychiatric disorders or hospitalized without consent for psychiatric care

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04822766

Contacts

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Contact: Rémy DULERY, MD	01 49 28 26 20	remy.dulery@aphp.fr
Contact: Mohamad MOHTY, PU-PH	01 49 28 26 20	mohamad.mohty@inserm.fr

Locations

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France
Saint Antoine Hospital - Hematology Department	Recruiting
Paris, France, 75012
Contact: Rémy DULERY, MD 01 49 28 26 20 remy.dulery@aphp.fr
Contact: Mohamad MOHTY, PU6PH 01 49 28 26 20 mohamad.mohty@inserm.fr

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

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Principal Investigator:	Rémy DULERY, MD	Assistance Publique - Hôpitaux de Paris

More Information

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Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT04822766
Other Study ID Numbers:	APHP200134 2020-A01456-33 ( Other Identifier: ANSM )
First Posted:	March 30, 2021 Key Record Dates
Last Update Posted:	January 25, 2022
Last Verified:	January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Assistance Publique - Hôpitaux de Paris:


Allogeneic hematopoietic cell transplantation acute myeloid leukemia

Additional relevant MeSH terms:

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Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms by Histologic Type Neoplasms

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