Acute Myelogenous LeukemiaPhase 2NCT02395822
MT2014-25: Haplo NK With SQ IL-15 in Adult Relapsed or Refractory AML Patients
A Phase 2 study testing IL-15 in people with Acute Myelogenous Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
A phase II trial of CD3/CD19 depleted, IL-15 activated, donor natural killer (NK) cells in adults and subcutaneous IL-15 given after a preparative regimen for the treatment of relapsed or refractory acute myelogenous leukemia (AML). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Myelogenous Leukemia
- What is being tested?
- IL-15
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2015to 1 Dec 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Meets ONE of the following disease criteria:
- Primary AML induction failure: no CR after 2 or more induction attempts
- Relapsed AML or Secondary AML (from MDS or treatment related): not in CR after 1 or more cycles of standard re-induction therapy
- AML relapsed > 2 months after transplant: No re-induction required, and no more than 1 re-induction cycle is allowed.
- Relapsed AML for patients > 60 years of age the 1 cycle of standard chemotherapy is not required if either of the following criteria is met:
- Relapse within 6 months of last chemotherapy
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- BM blast count < 30% within 10 days of starting protocol therapy
- Available related HLA-haploidentical donor (aged 14 to 75 years) by at least Class I serologic typing at the A\&B locus
- Karnofsky Performance Status ≥ 60%
- Patients must have adequate organ within 14 days (28 days for pulmonary and cardiac) of study registration
- Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to NK cell infusion (excluding preparative regimen pre-medications).
- Agrees to use contraception prior to study entry and for the duration of study participation.
Who cannot join
- Bi-phenotypic acute leukemia.
- Transplant < 60 days prior to study enrollment.
- Active autoimmune disease.
- History of severe asthma
- Uncontrolled intercurrent illness
- New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been evaluated with bronchoscopy
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- Pleural effusion large enough to be detectable on chest x-ray.
- Pregnant women
- History of HIV, active or chronic hepatitis B, hepatitis C or HTLV-I infection
- Known hypersensitivity to any of the study agents used
- Received investigational drugs within the 14 days of study registration.
- Known active CNS involvement.
- Criteria For Initial Donor Selection:
- Related donors (sibling, parent, offspring, parent or offspring of an HLA identical sibling).
- 14-75 years of age.
- At least 40 kilogram body weight.
- In general good health as determined by the evaluating medical provider.
- HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A\&B locus.
- Not pregnant.
- Able and willing to undergo apheresis.
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: MT2014-25: Haploidentical Donor Natural Killer (NK) Cell Infusion With Subcutaneous Recombinant Human IL-15 (rhIL-15) in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)
A phase II trial of CD3/CD19 depleted, IL-15 activated, donor natural killer (NK) cells in adults and subcutaneous IL-15 given after a preparative regimen for the treatment of relapsed or refractory acute myelogenous leukemia (AML). The primary objective is to study the potential efficacy of NK cells and IL-15 to achieve complete remission while maintaining safety.
- Conditions
- Acute Myelogenous Leukemia
- Being tested
- IL-15
- Keywords
- AML, Relapsed, Refractory
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IL-15Biological
Also called Interleukin-15
Preparative Regimen:
Fludarabine 25 mg/m2 x 5 days start day -6 Cyclophosphamide 60 mg/kg x 2 days on day -5 and -4 (if < 4 months from prior transplant, omit day -4 dose)
IL-15 Activated Donor NK Cells:
The apheresis product (collected day -1) will be enriched for NK cells with the large-scale CliniMacs® device (Miltenyi) by depletion of CD3+ cells to remove T-lymphocytes and depletion of CD19+ cells to remove B-lymphocytes. The NK cell enriched product will be activated by overnight incubation with10 ng/ml IL-15 under GMP conditions and infused on day 0.
IL-15 to Facilitate NK Cell Survival and Expansion:
IL-15 at 2 mcg/kg subcutaneously (SC) beginning day +1, once a day for 5 days followed by a 2 day rest, and then once a day for 5 days for 10 doses total
| Study group | Role | What they receive |
|---|---|---|
| Preparative Regimen and SubQ rHuIL-15 | Experimental | Preparative Regimen of Fludarabine and Cyclophosphamide
IL-15 Activation of Donor NK Cells:
IL-15 to Facilitate NK Cell Survival and Expansion Receives: Biological: IL-15 |
What is being measured
The primary outcome is the main question the study is designed to answer.
< 5% Marrow Blast, no Circulating Peripheral Blasts and Neutrophil Count of > 1 x 10^9/L
Without platelet recovery
Measured: Day 42 post NK cell infusion
Secondary outcomes (4)
In Vivo Expansion (>100) of NK Cells (Defined at CD56+/CD3- Lymphocytes)
Measured: Day 14 post NK cell infusion
Proportion of Patients Experiencing Grade, 3, 4, and 5 Toxicities (Assessed by CTCAE v. 4)
Measured: Days 1-5 and Days 8-12, 24 hours after the last IL-15 dose, Day +28, Day +42
Treatment Related Mortality
Measured: 6 months post-therapy
Number of Subjects Achieving Complete Response, Defined as in Vivo Donor Derived NK Cell Expansion of > 100 Donor Derived NK Cells.
Measured: Day 42 post NK cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2015 (estimated)
- Study start1 Oct 2015
- Primary completion1 Dec 2016
- Study completion1 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myelogenous LeukemiaStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey Miller, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02395822
- Sponsor's protocol ID
- 2014LS092
- Status last verified
- Dec 2017
- First submitted
- 16 Feb 2015
- Last updated
- 20 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Cooley S, He F, Bachanova V, Vercellotti GM, DeFor TE, Curtsinger JM, Robertson P, Grzywacz B, Conlon KC, Waldmann TA, McKenna DH, Blazar BR, Weisdorf DJ, Miller JS. First-in-human trial of rhIL-15 and haploidentical natural killer cell therapy for advanced acute myeloid leukemia. Blood Adv. 2019 Jul 9;3(13):1970-1980. doi: 10.1182/bloodadvances.2018028332.
PubMed 31266741
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MT2014-25: Haploidentical Donor Natural Killer (NK) Cell Infusion With Subcutaneous Recombinant Human IL-15 (rhIL-15) in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)
- ClinicalTrials.gov ID
- NCT02395822
- Acronym / sponsor ID
- 2014LS092
- Conditions
- Acute Myelogenous Leukemia
- Keywords
- AML, Relapsed, Refractory
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- 1 Oct 2015 (actual)
- Primary completion
- 1 Dec 2016 (actual)
- Study completion
- 1 Dec 2016 (actual)
- First posted
- 24 Mar 2015 (estimated)
- Results
- Posted 10 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A phase II trial of CD3/CD19 depleted, IL-15 activated, donor natural killer (NK) cells in adults and subcutaneous IL-15 given after a preparative regimen for the treatment of relapsed or refractory acute myelogenous leukemia (AML). The primary objective is to study the potential efficacy of NK cells and IL-15 to achieve complete remission while maintaining safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Preparative Regimen and SubQ rHuIL-15 | Experimental | Biological: IL-15Preparative Regimen of Fludarabine and Cyclophosphamide IL-15 Activation of Donor NK Cells: IL-15 to Facilitate NK Cell Survival and Expansion |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Meets ONE of the following disease criteria:
- Available related HLA-haploidentical donor (aged 14 to 75 years) by at least Class I serologic typing at the A\&B locus
- Karnofsky Performance Status ≥ 60%
- Patients must have adequate organ within 14 days (28 days for pulmonary and cardiac) of study registration
- Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to NK cell infusion (excluding preparative regimen pre-medications).
Key exclusion criteria (20 listed)
- Bi-phenotypic acute leukemia.
- Transplant < 60 days prior to study enrollment.
- Active autoimmune disease.
- History of severe asthma
- Uncontrolled intercurrent illness
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 |
|---|---|---|
| IL-15Also: Interleukin-15Preparative Regimen: Fludarabine 25 mg/m2 x 5 days start day -6 Cyclophosphamide 60 mg/kg x 2 days on day -5 and -4 (if < 4 months from prior transplant, omit day -4 dose) IL-15 Activated Donor NK Cells: The apheresis product (collected day -1) will be enriched for NK cells with the large-scale CliniMacs® device (Miltenyi) by depletion of CD3+ cells to remove T-lymphocytes and depletion of CD19+ cells to remove B-lymphocytes. The NK cell enriched product will be activated by overnight incubation with10 ng/ml IL-15 under GMP conditions and infused on day 0. IL-15 to Facilitate NK Cell Survival and Expansion: IL-15 at 2 mcg/kg subcutaneously (SC) beginning day +1, once a day for 5 days followed by a 2 day rest, and then once a day for 5 days for 10 doses total | Biological | Preparative Regimen and SubQ rHuIL-15 |
Primary outcome
< 5% Marrow Blast, no Circulating Peripheral Blasts and Neutrophil Count of > 1 x 10^9/L
Time frame: Day 42 post NK cell infusion
Without platelet recovery
4 secondary outcomes
In Vivo Expansion (>100) of NK Cells (Defined at CD56+/CD3- Lymphocytes)
Time frame: Day 14 post NK cell infusion
Proportion of Patients Experiencing Grade, 3, 4, and 5 Toxicities (Assessed by CTCAE v. 4)
Time frame: Days 1-5 and Days 8-12, 24 hours after the last IL-15 dose, Day +28, Day +42
Treatment Related Mortality
Time frame: 6 months post-therapy
Number of Subjects Achieving Complete Response, Defined as in Vivo Donor Derived NK Cell Expansion of > 100 Donor Derived NK Cells.
Time frame: Day 42 post NK cell infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31266741Cooley S, He F, Bachanova V, Vercellotti GM, DeFor TE, Curtsinger JM, Robertson P, Grzywacz B, Conlon KC, Waldmann TA, McKenna DH, Blazar BR, Weisdorf DJ, Miller JS. First-in-human trial of rhIL-15 and haploidentical natural killer cell therapy for advanced acute myeloid leukemia. Blood Adv. 2019 Jul 9;3(13):1970-1980. doi: 10.1182/bloodadvances.2018028332.
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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.
Jeffrey Miller, MD principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IL-15 in people with Acute Myelogenous Leukemia, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
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 12 inclusion and 20 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 20 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
< 5% Marrow Blast, no Circulating Peripheral Blasts and Neutrophil Count of > 1 x 10^9/L (time frame: Day 42 post NK cell infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02395822, which also lists 1 linked publication.
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 20 Feb 2018.