Injection of Lymphocytes From Haplo-identical Donor Following Chemotherapy in Patients With High-risk Acute Myeloblastic Leukemia Not Eligible for an Allogeneic Hematopoietic Stem Cell Transplantation (ILDA)

Phase I Study Testing the Injection of Lymphocytes From Haplo-identical Donor Following Chemotherapy in Patients With High-risk Acute Myeloblastic Leukemia Not Eligible for an Allogeneic Hematopoietic Stem Cell Transplantation

Patients with high risk AML non eligible for an intensive treatment and for an allogeneic transplantation will be treated with azacitidine and venetoclax. The fourth, fifth and sixth injection of azacitidine will be followed by injection of haplo-identical lymphocytes (HLI). This is a single-center phase I study to identify the dose of HLI with the most tolerable toxicity. TheBayesian continuous reassessment method (CRM) will be used

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Biological: DLI

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Thierry Guillaume; Phone Number: 02 40 08 49 45; Email: thierry.guillaume@chu-nantes.fr

Study Locations

• France
  • Nantes, France, 44000
    • Recruiting
    • CHU de Nantes
    • Contact: Thierry Guillaume; Phone Number: 0240084945; Email: thierry.guillaume@chu-nantes.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age ≥18 years
• patients with de novo or secondary AML, with an unfavorable or intermediate karyotype (according to the 2017 ELN classification), or patients with relapsing AML who may receive second-line treatment

• not candidates for intensive induction, for the following reasons

  • 75 years or ≥ 18 to 74 years and at least one of the following comorbidities: PS ≥ 2 or a history of heart failure requiring treatment or LVEF ≤ 50% or chronic stable angina or FEV1 ≤ 65% or DLCO ≤ 65% or creatinine clearance <45 ml / min; or liver damage with total bilirubin> 1.5 N or other comorbidities that the hematologist considers incompatible with intensive treatment
• ineligible for a classic allogeneic hematopoietic stem cell transplant due to the presence of co-morbidities or too high a risk of toxicity >70 years old or at least one of the following comorbidities: PS ≥ 2 or a history of heart failure requiring treatment or LVEF ≤ 50% or chronic stable angina or FEV1 ≤ 65% or DLCO ≤ 65% or creatinine clearance <45 ml / min; or liver damage with total bilirubin> 1.5 N
• may receive chemotherapy with hypomethylating agents have a partially compatible (haplo-identical) major family donor (≥18 years old) eligible for lymphocyte donation.

Exclusion Criteria:

• AML with favorable karyotype (according to ELN 2017) in RC1
• Patient with refractory or progressive AML
• Other progressive cancer in progress
• Karnosky index <60% or PS> 2
• Severe hepatic function disturbance: transaminases> 5 N, hyperbilirubinemia> 30 µm / L
• Severe infection requiring hospitalization.
• Psychiatric illness compromising the understanding of the information or the carrying out of the study.
• woman of childbearing potential and refusing an effective method of contraception.
• Minor
• Adult under tutorship or curatorship, under legal protection or under family authorization
• Minor family donor (<18 years old)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
number of DLT	by day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
cumulative incidence of relapse	1 YEAR
relapse-free survival	1 YEAR
overall survival	1 YEAR

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Thierry Guillaume, CHU de Nantes

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2021
• Primary Completion (Anticipated): November 1, 2024
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 13, 2021

Study Record Updates

• Last Update Posted (Actual): May 11, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Leukemia; Leukemia, Myeloid, Acute
• Other Study ID Numbers: RC20_0357

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No