Phase I Study of Adoptive Immunotherapy With Enriched and Expanded Autologous Natural Killer (NK) Cells for Patients With Ph+ Acute Lymphoblastic Leukemia (ALL)

NCT ID: NCT02185781

Last Updated: 2023-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-28
• Study Completion Date: 2021-11-29

Brief Summary

The present study aims at studying how safe and tolerable a new therapy for patients with Acute Lymphoblastic Leukemia (ALL) is.

This new therapy consists of an immunotherapy, that is an approach focusing on the immune system, and it targets ALL patients in complete remission but who may still have the disease at a cellular level (this is called 'minimal residual disease').

For any further information, please, discuss with your treating physician.

Detailed Description

This is an open label, multicenter, phase I study of adoptive immunotherapy with enriched and expanded autologous natural killer (NK) cells for patients with Ph+ acute lymphoblastic leukemia (ALL) in complete hematologic remission (CHR) but with persistent/recurrent minimal residual disease (MRD) ≥60 years or not eligible for other post-CHR treatment modalities.

The study will investigate the safety and tolerability of a new type of NK-based immunotherapy based on the infusion of escalating doses of ex-vivo expanded autologous NK cells in Ph+ ALL patients. A maximum of 6 patients will be enrolled in two different steps. No conditioning therapies will be administered before the infusion of the expanded NK cells. Patients may receive tyrosine kinase inhibitor (TKI) maintenance.

Conditions

Acute Lymphoblastic Leukemia; Complete Hematologic Remission (CHR); Persistent/Recurrent Minimal Residual Disease (MRD)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Autologous NK Cells infusions

Group Type: EXPERIMENTAL

Autologous NK cells infusions

Intervention Type: OTHER

Each patient will receive repeated intravenous (IV) infusions of escalating doses of expanded autologous NK cells.

The initial dose will be 1 x 106/kg of recipient body weight (BW), followed by half log increments of the dose level for each infusion, to a maximum of 1 x 108/kg of recipient BW or until they experience any toxicity, for a maximum of 5 infusions. The minimum interval between each infusion will be 28 days. No conditioning therapies will be administered before the infusion of the expanded NK cells. Patients may receive TKI maintenance.

Interventions

Autologous NK cells infusions

Each patient will receive repeated intravenous (IV) infusions of escalating doses of expanded autologous NK cells.

The initial dose will be 1 x 106/kg of recipient body weight (BW), followed by half log increments of the dose level for each infusion, to a maximum of 1 x 108/kg of recipient BW or until they experience any toxicity, for a maximum of 5 infusions. The minimum interval between each infusion will be 28 days. No conditioning therapies will be administered before the infusion of the expanded NK cells. Patients may receive TKI maintenance.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adult subjects with Ph+ ALL in CHR (1st or 2nd) with MRD positivity confirmed at baseline, older or equal to 60 years or not eligible for other post-CHR treatment modalities.
• WHO score 0-1.
• Hematopoietic, liver and renal normal functions defined as follows:

WBC bigger or equal to 2.000/mm3 lymphocytes bigger or equal to 500/mm3 neutrophils bigger or equal to 1.000/mm3 platelets bigger or equal to 50.000/mm3 Hb bigger or equal to 9 g/dl creatinine fewer or equal to 1.5 x ULN bilirubin fewer or equal to 1.5 x ULN AST and ALT less than 3 times the upper limit of normal. LDH less than 2 times the upper limit of normal.

• For male and female subjects of childbearing potential, agreement to use effective contraception.
• Authorization by Istituto Superiore di Sanità (ISS) according to DM 2 March 2004.
• Signed written informed consent according to ICH/EU/GCP and national local regulations.

Exclusion Criteria

• Concurrent chemotherapy or immunotherapy (TKI maintenance is permitted).
• Any contraindications to perform a leukapheretic procedure for mononuclear cell collection.
• Active or chronic infection, including Treponema, HIV, HBV and/or HCV unless antigen/PCR negative.
• Presence of autoimmune symptoms.
• Pregnant or lactating females.
• Simultaneous participation in another clinical trial.
• Any physical or psychological impediment in a patient that could lead the investigator to suspect his/her poor compliance to the protocol.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roberto Foà

Role: STUDY_CHAIR

Policlinico Umberto I di Roma

Giovanni Torelli

Role: STUDY_DIRECTOR

Policlinico Umberto I di Roma

Locations

ISS/AIFA

Roma, , Italy

Ospedale S. Eugenio

Roma, , Italy

Università Cattolica del Sacro Cuore - Policlinico A. Gemelli

Roma, , Italy

Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia

Roma, , Italy

Università degli Studi - Policlinico di Tor Vergata

Roma, , Italy

Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia

Roma, , Italy

Countries

Italy

Other Identifiers

LAL 2013

Identifier Type: -

Identifier Source: org_study_id