Acute Lymphoblastic LeukemiaPhase 1NCT02185781
Phase I Study of Adoptive Immunotherapy With Enriched and Expanded Autologous Natural Killer (NK) Cells for Patients With Ph+ Acute Lymphoblastic Leukemia (ALL)
A Phase 1 study testing Autologous NK cells infusions in people with Acute Lymphoblastic Leukemia and Complete Hematologic Remission (CHR), run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 6 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Complete Hematologic Remission (CHR), Persistent/Recurrent Minimal Residual Disease (MRD)
- What is being tested?
- Autologous NK cells infusions
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 6 sitesItaly
- Study dates
- 28 Jan 2015to 29 Nov 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Italy6 sites
ISS/AIFA
Roma
Ospedale S. Eugenio
Roma
Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
Roma
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
Roma
Università degli Studi - Policlinico di Tor Vergata
Roma
Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia
Roma
About this study
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
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.
Read the 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)
- Being tested
- Autologous NK cells infusions
- 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
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous NK cells infusionsOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Autologous NK Cells infusions | Experimental | Not described Receives: Other: Autologous NK cells infusions |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the MTD and the recommended final dose (RD) to be used for further investigations.
Measured: One year from start of treatment.
Secondary outcomes (7)
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.
Measured: Two years from start of treatment.
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.
Measured: One year from start of treatment.
Time to complete enrolment.
Protocol feasibility.
Measured: Three years from first patient enrollment.
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.
Measured: One year from start of treatment.
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.
Measured: One year from treatment start.
Number of patients alive after treatment conclusion.
To evaluate OS in terms of number of patients alive.
Measured: Two years from treatment start.
Number of patients alive without progression.
To evaluate the TTP in terms of number of patients alive without progression.
Measured: One year from treatment start.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2014 (estimated)
- Study start28 Jan 2015
- Primary completionNov 2021
- Study completion29 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'Adulto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Roberto Foà, Study chair, Policlinico Umberto I di RomaGiovanni Torelli, Study director, Policlinico Umberto I di Roma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02185781
- Sponsor's protocol ID
- LAL 2013
- Status last verified
- Mar 2023
- First submitted
- 7 Jul 2014
- Last updated
- 30 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02185781
- Acronym / sponsor ID
- LAL 2013
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'AdultoUniversity, hospital or other
- Study start
- 28 Jan 2015 (actual)
- Primary completion
- Nov 2021 (actual)
- Study completion
- 29 Nov 2021 (actual)
- First posted
- 10 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Autologous NK Cells infusions | Experimental | Other: Autologous NK cells infusions |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous NK cells infusionsEach 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. | Other | Autologous NK Cells infusions |
Primary outcome
To determine the MTD and the recommended final dose (RD) to be used for further investigations.
Time frame: One year from start of treatment.
7 secondary outcomes
Number of adverse events.
Time frame: Two years from start of treatment.
Number of patients able to complete the study.
Time frame: One year from start of treatment.
Time to complete enrolment.
Time frame: Three years from first patient enrollment.
Number and characteristics of immunologic modifications.
Time frame: One year from start of treatment.
Number of patients who respond to treatment.
Time frame: One year from treatment start.
Number of patients alive after treatment conclusion.
Time frame: Two years from treatment start.
Number of patients alive without progression.
Time frame: One year from treatment start.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roberto Foà study chair
Policlinico Umberto I di Roma
Giovanni Torelli study director
Policlinico Umberto I di Roma
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous NK cells infusions in people with Acute Lymphoblastic Leukemia and Complete Hematologic Remission (CHR), run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 6 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the MTD and the recommended final dose (RD) to be used for further investigations. (time frame: One year from start of treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2023; AzTrials last refreshed its copy on 31 Oct 2026.