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

Primary Purpose

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

Status
Completed
Phase
Phase 1
Locations
Italy
Study Type
Interventional
Intervention
Autologous NK cells infusions
Sponsored by
Gruppo Italiano Malattie EMatologiche dell'Adulto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring 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

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • ISS/AIFA
  • Ospedale S. Eugenio
  • Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
  • Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
  • Università degli Studi - Policlinico di Tor Vergata
  • Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Autologous NK Cells infusions

Arm Description

Outcomes

Primary Outcome Measures

To determine the MTD and the recommended final dose (RD) to be used for further investigations.

Secondary Outcome Measures

Number of adverse events.
To assess the safety and tolerabilty of the treatment by evaluating frequency, type and intensity of adverse events (AEs) according to the CTC classification, as well as the patients' compliance and clinically relevant changes in the laboratory parameters.
Number of patients able to complete the study.
To evaluate the feasibility of the procedure in terms of number of patients able to complete the study and time to complete enrolment.
Time to complete enrolment.
Protocol feasibility.
Number and characteristics of immunologic modifications.
To assess the immunologic modifications induced by the procedure; in particular, to verify the functional and cytotoxic activity against tumor cell lines and primary fresh allogeneic and autologous blasts cryopreserved at diagnosis, and to monitor the frequency, phenotype and activation status of the infused NK cell populations by flow cytometry analyses, Chromium release cytotoxic assays and intracellular cytokine production.
Number of patients who respond to treatment.
To evaluate the clinical response to the treatment in terms of control of MRD with quantitative (Q)- RT-PCR.
Number of patients alive after treatment conclusion.
To evaluate OS in terms of number of patients alive.
Number of patients alive without progression.
To evaluate the TTP in terms of number of patients alive without progression.

Full Information

First Posted
July 7, 2014
Last Updated
March 29, 2023
Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto
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1. Study Identification

Unique Protocol Identification Number
NCT02185781
Brief Title
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
January 28, 2015 (Actual)
Primary Completion Date
November 2021 (Actual)
Study Completion Date
November 29, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Autologous NK Cells infusions
Arm Type
Experimental
Intervention Type
Other
Intervention Name(s)
Autologous NK cells infusions
Intervention Description
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.
Primary Outcome Measure Information:
Title
To determine the MTD and the recommended final dose (RD) to be used for further investigations.
Time Frame
One year from start of treatment.
Secondary Outcome Measure Information:
Title
Number of adverse events.
Description
To assess the safety and tolerabilty of the treatment by evaluating frequency, type and intensity of adverse events (AEs) according to the CTC classification, as well as the patients' compliance and clinically relevant changes in the laboratory parameters.
Time Frame
Two years from start of treatment.
Title
Number of patients able to complete the study.
Description
To evaluate the feasibility of the procedure in terms of number of patients able to complete the study and time to complete enrolment.
Time Frame
One year from start of treatment.
Title
Time to complete enrolment.
Description
Protocol feasibility.
Time Frame
Three years from first patient enrollment.
Title
Number and characteristics of immunologic modifications.
Description
To assess the immunologic modifications induced by the procedure; in particular, to verify the functional and cytotoxic activity against tumor cell lines and primary fresh allogeneic and autologous blasts cryopreserved at diagnosis, and to monitor the frequency, phenotype and activation status of the infused NK cell populations by flow cytometry analyses, Chromium release cytotoxic assays and intracellular cytokine production.
Time Frame
One year from start of treatment.
Title
Number of patients who respond to treatment.
Description
To evaluate the clinical response to the treatment in terms of control of MRD with quantitative (Q)- RT-PCR.
Time Frame
One year from treatment start.
Title
Number of patients alive after treatment conclusion.
Description
To evaluate OS in terms of number of patients alive.
Time Frame
Two years from treatment start.
Title
Number of patients alive without progression.
Description
To evaluate the TTP in terms of number of patients alive without progression.
Time Frame
One year from treatment start.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roberto Foà
Organizational Affiliation
Policlinico Umberto I di Roma
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Giovanni Torelli
Organizational Affiliation
Policlinico Umberto I di Roma
Official's Role
Study Director
Facility Information:
Facility Name
ISS/AIFA
City
Roma
Country
Italy
Facility Name
Ospedale S. Eugenio
City
Roma
Country
Italy
Facility Name
Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
City
Roma
Country
Italy
Facility Name
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
City
Roma
Country
Italy
Facility Name
Università degli Studi - Policlinico di Tor Vergata
City
Roma
Country
Italy
Facility Name
Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia
City
Roma
Country
Italy

12. IPD Sharing Statement

Learn more about this trial

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

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