Clinical trial NCT02185781: Phase I Study of Adoptive Immunotherapy With Enriched and Expanded Autologous Natural Killer (NK) Cells for Patients With Ph+ Acute Lymphoblastic Leukemia (ALL)
Official title: Phase I Protocol 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia
Complete Hematologic Remission (CHR)
Persistent/Recurrent Minimal Residual Disease (MRD)
Keywords: Phase I
Adoptive immunotherapy
Enriched and expanded autologous natural killer (NK) cells
Ph+ acute lymphoblastic leukemia
≥60 years
Not eligible for other post-CHR treatment modalities
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2014-07-10
Enrollment: 6
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: To determine the MTD and the recommended final dose (RD) to be used for further investigations.
timeFrame: One year from start of treatment.
Secondary outcomes:
measure: Number of adverse events.
timeFrame: Two years from start of treatment.
measure: Number of patients able to complete the study.
timeFrame: One year from start of treatment.
measure: Time to complete enrolment.
timeFrame: Three years from first patient enrollment.
measure: Number and characteristics of immunologic modifications.
timeFrame: One year from start of treatment.
measure: Number of patients who respond to treatment.
timeFrame: One year from treatment start.
measure: Number of patients alive after treatment conclusion.
timeFrame: Two years from treatment start.
measure: Number of patients alive without progression.
timeFrame: One year from treatment start.
Other outcomes:
Locations:
city: Roma
country: Italy
facility: ISS/AIFA
city: Roma
country: Italy
facility: Ospedale S. Eugenio
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
city: Roma
country: Italy
facility: Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
city: Roma
country: Italy
facility: Università degli Studi - Policlinico di Tor Vergata
city: Roma
country: Italy
facility: Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia
Study officials:
affiliation: Policlinico Umberto I di Roma
name: Roberto Foà
role: STUDY_CHAIR
affiliation: Policlinico Umberto I di Roma
name: Giovanni Torelli
role: STUDY_DIRECTOR
References: