Clinical trial NCT04886206: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Acute Myeloid Leukemia (AML)
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2021-05-13
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Continual Reassessment Method for MTD
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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)

Primary outcomes:
measure: number of DLT
timeFrame: by day 14
Secondary outcomes:
measure: cumulative incidence of relapse
timeFrame: 1 YEAR
measure: relapse-free survival
timeFrame: 1 YEAR
measure: overall survival
timeFrame: 1 YEAR
Other outcomes:
Locations:
city: Nantes
country: France
facility: CHU de Nantes
Study officials:
affiliation: Nantes University Hospital
name: Thierry Guillaume
role: PRINCIPAL_INVESTIGATOR
References: