Sequential Conditioning in Haploidentical Transplantation for Refractory Acute Myeloid Leukemia

NCT03035422 | Completed

• 1 other identifier: 2016-A00862-49
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment option with a significant chance of healing in acute myeloid leukemia (AML) or refractory multiple relapses after chemotherapy. However, all patients with an indication of allo-HSC can not benefit because of two limitations: the toxicity of the treatment and graft shortage available.

Conditions

Refractory Acute Myeloid Leukemia

Keywords

Allogenic cell stem transplant, Sequential chemotherapy Haploidentical transplant

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  The aim is to describe the efficacy of the combination of a SET followed by haploidentical transplant with post-transplant immune modulation by pDLI in patients with AML. The main objective is to assess overall survival at 2 years in these patients.

  2 years after transplantation

Secondary Outcomes (7)

• Partial or complete remission rate by standard criteria Relapse incidence and death related to the disease

  90 days and then 6, 12 and 24 months after transplantation

• Cumulative incidence of death not related to relapse

  90 days and then 12 and 24 months after transplantation

• Cumulative incidence of acute and chronic graft against host disease (GVHD)

  100 days and then 12 and 24 months after transplantation

• Number of patients for whom pDLI was possible.

  2 years after transplantation

• Study of immune reconstitution post-transplant in the peripheral blood will be used:CD4 lymphocyte levels, CD8, T regulators, Natural Killer cells and B cells

  90 days and then 6, 12 and 24 months after transplantation

Study Arms (1)

Patients with primary refractory acute myeloid leukemia

OTHER

Patients with primary refractory acute myeloid leukemia

Drug: Sequential Packaging (SET); Drug: Transfusion graft; Drug: Prevention of GVHD; Drug: Care supports; Drug: Lymphocyte injection of prophylactic donor (PDLI)

Interventions

Sequential Packaging (SET) DRUG

Sequential chemotherapy: * Thiotepa 5 mg / kg / day for 1 day (D-13) * Cyclophosphamide 400 mg / m² / day for 4 days (J-12 to J-9) * Etoposide 100 mg / m² / day for 4 days (J-12 to J-9) Repos days J-8 and J-6 Reduced-intensity conditioning (RIC) * Fludarabine 30 mg / m² / day for 5 days (J-5 to D-1) * Busulfan IV 3.2 mg / kg / day for 2 days (J-5 and J-4) * Anti-lymphocyte serum (Thymoglobuline) 2.5 mg / kg / day for 2 days (J-3 and J-2)

Patients with primary refractory acute myeloid leukemia

Transfusion graft DRUG

Graft of peripheral stem cells is preferred at D0

Patients with primary refractory acute myeloid leukemia

Prevention of GVHD DRUG

* Cyclophosphamide 50mg / kg / day on days D + 3 and D + 5 * Cyclosporine A (CSA; 3 mg / kg / day IV from D + 6) * Mycophenolate mofetil (MMF; 30 mg / kg / day, maximum x2 1g / day from day J + 6)

Patients with primary refractory acute myeloid leukemia

Care supports DRUG

According to the protocols of each center

Patients with primary refractory acute myeloid leukemia

Lymphocyte injection of prophylactic donor (PDLI) DRUG

According to the protocols of each center. In the absence of clinical indication against-disease (GVHD), phasing MMF between days D + 35 and D + 56, then phasing APF between D + 62 and D + 90 \- PDLI: 3 injections from the D + 120 patients who discontinued immunosuppressive therapy for ≥ 1 month and having no active GVHD or history of acute GVHD grade\> II

Patients with primary refractory acute myeloid leukemia

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with a confirmed diagnosis of acute myeloid leukemia after primary induction treatment failure (persistent leukemia after 2 cycles of induction chemotherapy)
• Patient age ≥ 18 to \<60 years
• Cardiac ejection fraction of the left ventricle ≥ 45%
• Lung function - free diffusion capacity for carbon monoxide ≥ 50% of predicted value
• Creatinine clearance ≥ 50 ml / min depending on the CKD-EPI formula
• Availability of an HLA haploidentical donor in the family
• Collection of non-opposition

You may not qualify if:

• Uncontrolled invasion of CNS
• Availability of an HLA identical family donor who agreed to donate hematopoietic stem cells OR non-related donor HLA-compatible 10/10 on HLA-A alleles, B, C, and DRB1 DQB1 available and ready to give in 4 weeks to make a decision allograft
• Presence in the patient HLA-specific antibodies directed against an antigen HLA haploidentical donor family
• Karnofsky score \<70%
• Patient HIV positive
• Hepatitis B or C or chronic active
• Uncontrolled infection at the time of start packing
• Contraindication to the use of treatments provided by the Protocol
• Previous history of allo-HSC
• No beneficiary of a social security scheme.

Sponsors & Collaborators

• Association for Training, Education, and Research in Hematology, Immunology, and Transplantation: lead

Study Sites (1)

Service d'hématologie Clinique Hôpital Saint Antoine

Paris, 75012, France

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 Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2016
• First Posted: January 30, 2017
• Study Start: January 15, 2018
• Primary Completion: December 18, 2021
• Study Completion: December 18, 2021
• Last Updated: July 25, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)