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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)

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ClinicalTrials.gov Identifier: NCT02185781
Recruitment Status : Unknown
Verified August 2018 by Gruppo Italiano Malattie EMatologiche dell'Adulto.
Recruitment status was:  Recruiting
First Posted : July 10, 2014
Last Update Posted : August 6, 2018
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

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.


Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Complete Hematologic Remission (CHR) Persistent/Recurrent Minimal Residual Disease (MRD) Other: Autologous NK cells infusions Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 2014
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : October 2018


Arm Intervention/treatment
Experimental: Autologous NK Cells infusions Other: 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.





Primary Outcome Measures :
  1. 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 Measures :
  1. Number of adverse events. [ Time Frame: Two years from start of treatment. ]
    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.

  2. Number of patients able to complete the study. [ Time Frame: One year from start of treatment. ]
    To evaluate the feasibility of the procedure in terms of number of patients able to complete the study and time to complete enrolment.

  3. Time to complete enrolment. [ Time Frame: Three years from first patient enrollment. ]
    Protocol feasibility.

  4. Number and characteristics of immunologic modifications. [ Time Frame: One year from start of treatment. ]
    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.

  5. Number of patients who respond to treatment. [ Time Frame: One year from treatment start. ]
    To evaluate the clinical response to the treatment in terms of control of MRD with quantitative (Q)- RT-PCR.

  6. Number of patients alive after treatment conclusion. [ Time Frame: Two years from treatment start. ]
    To evaluate OS in terms of number of patients alive.

  7. Number of patients alive without progression. [ Time Frame: One year from treatment start. ]
    To evaluate the TTP in terms of number of patients alive without progression.



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02185781


Contacts
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Contact: Paola Fazi, PhD p.fazi@gimema.it
Contact: Enrico Crea e.crea@gimema.it

Locations
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Italy
ISS/AIFA Not yet recruiting
Roma, Italy
Contact: Annarita Meneguz         
Principal Investigator: Annarita Meneguz         
Ospedale S. Eugenio Recruiting
Roma, Italy
Contact: Paolo DE FABRITIIS, Pr.         
Principal Investigator: Paolo DE FABRITIIS, Pr.         
Sub-Investigator: Benedetta Neri         
Università Cattolica del Sacro Cuore - Policlinico A. Gemelli Recruiting
Roma, Italy
Contact: Livio Pagano         
Principal Investigator: Livio Pagano         
Sub-Investigator: Luana Fianchi         
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia Recruiting
Roma, Italy
Contact: Roberto Foà         
Principal Investigator: Roberto Foà         
Sub-Investigator: Giovanni Torelli         
Università degli Studi - Policlinico di Tor Vergata Not yet recruiting
Roma, Italy
Contact: Adriano Venditti         
Principal Investigator: Adriano Venditti, dr.         
Sub-Investigator: Ilaria Del Principe, Dr.         
Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
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Study Chair: Roberto Foà Policlinico Umberto I di Roma
Study Director: Giovanni Torelli Policlinico Umberto I di Roma
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Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT02185781    
Other Study ID Numbers: LAL 2013
First Posted: July 10, 2014    Key Record Dates
Last Update Posted: August 6, 2018
Last Verified: August 2018
Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
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
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasm, Residual
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes