Back to resultsInjection 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)
Primary Purpose
Acute Myeloid Leukemia (AML)
Status
Recruiting
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
DLI
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia (AML)
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)
Sites / Locations
- CHU de NantesRecruiting
Outcomes
Primary Outcome Measures
number of DLT
Secondary Outcome Measures
cumulative incidence of relapse
relapse-free survival
overall survival
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04886206
Brief Title
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
Acronym
ILDA
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
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 10, 2021 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Continual Reassessment Method for MTD
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Biological
Intervention Name(s)
DLI
Intervention Description
the patients will receive the injection of donor lymphocytes from haplo-identical donor (the son or daughter or possibly nephew or niece of the patient). No immunosuppressive drugs will be used. The HLI dose levels are 1) 1x107 CD3+/kg 2) 5x107 CD3+/kg 3) 7.5x107 CD3+/kg 4) 1x108 CD3+/kg.The CRM method (Continual Reassessment Method) was chosen to specify the dose of cells to be injected, each patient being assigned a dose that is believed to be associated with the target toxicity corresponding to the maximum tolerated dose (MTD). The dose-toxicity curve will be readjusted after assessing the toxicity of each patient.
Primary Outcome Measure Information:
Title
number of DLT
Time Frame
by day 14
Secondary Outcome Measure Information:
Title
cumulative incidence of relapse
Time Frame
1 YEAR
Title
relapse-free survival
Time Frame
1 YEAR
Title
overall survival
Time Frame
1 YEAR
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thierry Guillaume
Phone
02 40 08 49 45
Email
thierry.guillaume@chu-nantes.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thierry Guillaume
Organizational Affiliation
Nantes University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Nantes
City
Nantes
ZIP/Postal Code
44000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thierry Guillaume
Phone
0240084945
Email
thierry.guillaume@chu-nantes.fr
12. IPD Sharing Statement
Learn more about this trial
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
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