Haploidentical Stem Cell Transplant With or Without NK Cell Infusion in AML and MDS (Bigeminy)

Haploidentical Stem Cell Transplantation With or Without NK Cell Infusion in Refractory/Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome:The BigEMINy Study

Relapse after an allogeneic hematopoietic stem cell transplantation (HSCT) is high in patients with advanced AML, in the 50% range. NK cells have been shown to possess significant anti-leukemic activity and may be used to reduce the incidence of relapse in patients with advanced AML.

Investigators hypothesize that the administration of a purified boost of NK cells on day +7 post HSCT, will reduce the incidence of relapse from the current 50% to 25%. In a phase III multicenter clinical study, 116 patients will be randomized to receive or not a boost of donor NK cells on day +7 post-HSCT. The first 10 patients in the experimental arm will be analyzed for toxicity. The stopping rule will be a transplant related mortality of more than 50% in the first 20 patients who received NK cells.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Myelodysplasia
• Intervention / Treatment: Biological: Haplo SCT with NK cells; Biological: Haplo SCT

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andrea Bacigalupo, Prof; Phone Number: +390630154180; Email: andrea.bacigalupo@unicatt.it
• Study Contact Backup: Name: Luciana Teofili, Dr; Email: luciana.teofili@unicatt.it

Study Locations

• Italy
  • RM
    • Roma, RM, Italy, 00168
      • Fondazione Policlinico Universitario A. Gemelli IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of AML or MDS
• Patients not in remission at the time of transplant
• Age 18-75
• ECOG performance status <2
• Availability of a family HLA haploidentical donor, eligible to donate both marrow cells and unstimulated lymphocytes (1 apheresis procedure at day +7) .

Exclusion Criteria:

• Positive serologic markers for human immunodeficiency virus (HIV)
• Acute hepatitis B virus (HBV) or acute hepatitis C virus (HCV) infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Haplo-stem cell transplant followed by NK infusion; Haplo stem cell transplant (from bone marrow or apheresis) is followed by a haplo-NK cell infusion (target dose ≥1*106/kg b.w.) at day 7. Unstimulated haplo-NK cells are collected through apheresis Mononuclear cells are then subjected to a preliminary negative selection of CD3+ cells and to a subsequent positive selection of CD56+ cells. CD3 negative/CD56 positive cells are infused	Biological: Haplo SCT with NK cells; Patients in this arm receive haplo-SCT followed by one boost of NK cells one/two weeks after the transplant. Lymphocyte are collected by apheresis from the donor one-two weeks after BM harvest. CD3 negative/CD56 positive cells are selected by immunomagnetic columns (other lymphocytes are stored to be used as DLI); Other Names: haplo SCT followed by NK cell infusion
Active Comparator: Haplo-stem cell transplant; Patients in this arm receive standard haplo stem cell transplant (from bone marrow or apheresis) transplant without subsequent NK cell infusion.	Biological: Haplo SCT; Patients in this arm receive a standard haplo-SCT. All administerd therapies are the same as in other arm, except for the NK cell boost..; Other Names: Standard haplo SCT without subsequent NK cell boost.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leukemia relapse	Cumulative incidence of leukemia relapse.	1 year after bone marrow transplant

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Collaborators: Ministry of Health, Italy
• Investigators: Principal Investigator: Andrea Bacigalupo, Prof, Fondazione Policlinico Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Actual): September 28, 2023
• Study Completion (Actual): September 28, 2023

Study Registration Dates

• First Submitted: November 14, 2019
• First Submitted That Met QC Criteria: November 15, 2019
• First Posted (Actual): November 18, 2019

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia
• Other Study ID Numbers: 2588 (Nederlands trial register)

Drug and device information, study documents

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