Acute Myeloid LeukemiaPhase 2NCT01370213
NK Cell Based Non-Myeloablative Transplantation in Acute Myeloid Diseases
A Phase 2 study testing Preparative Regimen, NK Cells and Interleukin-2 in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Masonic Cancer Center, University of Minnesota at 4 sites in United States.
Trial summary
This is a phase II multi-institutional therapeutic study of NK-cell based nonmyeloablative haploidentical transplantation for the treatment of high-risk acute myeloid diseases. Enrollment will use a two-stage design. Stage 1 will enroll 15 patients unless an early stopping rule is met. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- What is being tested?
- Preparative Regimen, NK Cells and Interleukin-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 4 sitesUnited States
- Study dates
- Sep 2011to Apr 2017
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)
- RAEB-1 or RAEB-2 fitting within one of the following disease groups:
- Primary induction failure (PIF): Patients who have not achieved a complete remission (CR) after two induction cycles of cytotoxic therapy (i.e. 7+ 3, MEC, FLAG, etc.) and having ≤ 10,000 absolute circulating blasts measured at least 21 days from prior therapy. Hydroxyurea may be used to control blasts count. Demethylating agents do not count as induction therapy; however early re-induction therapy based on residual disease on a day 14 BM will count as a 2nd cycle
- Relapsed Disease with low disease burden (AML or MDS with ≤ 10,000 absolute circulating blasts. No re-induction attempts are required, but a maximum of 2 reinduction attempts are allowed to be eligible.
- CR3 or greater: This will include CRp defined as CR without platelet recovery to 100,000/mcL.
- CR1 or CR2 with high risk features: Includes therapy induced, prior MDS or MPD, high risk cytogenetic or molecular phenotype with no available donor (sibling or unrelated adult)
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- Patients with known prior central nervous system (CNS) involvement are eligible provided that it has been treated and CSF is clear for at least 2 weeks prior to enrollment. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment.
- Available related HLA-haploidentical adult donor by at least Class I serologic typing at the A\&B locus
- Karnofsky score > 50%
- Adequate organ function within 28 days of study registration defined as:
- Hepatic: AST ≤ 3 x upper limit of institutional normal, total bilirubin ≤ 2.0 mg/dl
- Renal: estimated glomerular filtration rate (GFR) ≥ 50 mL/min/1.73m^2
- Pulmonary: Oxygen saturation ≥ 90% on room air and DLCOcor ≥ 40%
- Cardiac: Ejection Fraction ≥ 35% and no uncontrolled angina, severe uncontrolled ventricular or arterial arrhythmias, or any evidence of acute ischemia or active conduction system abnormalities (rate controlled atrial fibrillation is not an exclusion)
- Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to NK cell infusion (except for those prescribed as part of the study)
- Women of child bearing potential must have a negative pregnancy test within 28 days prior to study registration and agree to use adequate birth control during study treatment
- Voluntary written consent
Who cannot join
- Biphenotypic leukemia
- Allogeneic transplant for AML within previous 6 months
- New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been evaluated with bronchoscopy, if feasible. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
- Uncontrolled bacterial, fungal or viral infections including HIV - chronic asymptomatic viral hepatitis is allowed
- Known hypersensitivity to any of the study agents
- Received any investigational drugs within the 14 days before 1st dose of fludarabine
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- Requires agents other than hydroxyurea to control blast count
- Donor Selection:
- Related donor (sibling, parent, offspring, parent or offspring of an HLA identical sibling) 12-75 years of age. (It is recognized individual institutions may have differing donor age guidelines. This is acceptable as long as no donor is younger than 12 years or older than 75 years).
- Body weight of at least 40 kilograms
- In general good health as determined by the medical provider
- HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A\&B locus
- Able and willing to have up to 4 separate apheresis collections
- Not pregnant
- Voluntary written consent
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory University
Atlanta, Georgia, 30322
Ohio State University
Columbus, Ohio, 43210
University of Minnesota, Masonic Cancer Center
Minneapolis, Minnesota, 55455
Washington University
St Louis, Missouri, 63110
About this study
Official title: Multi-Center Phase II Trial of NK Cell Based Non-Myeloablative Haploidentical Transplantation for Patients With High-Risk Acute Myeloid Diseases
This is a phase II multi-institutional therapeutic study of NK-cell based nonmyeloablative haploidentical transplantation for the treatment of high-risk acute myeloid diseases. Enrollment will use a two-stage design. Stage 1 will enroll 15 patients unless an early stopping rule is met. If 9 or more of these first 15 patients achieve leukemia free neutrophil engraftment at day +28 accrual will move to stage 2. In stage 2, an additional 28 patients will be enrolled for a total of 43 patients. Patients will be followed for disease response for 2 years.
Read the detailed description
A reduced intensity conditioning using Fludara, Cytoxan, and irradiation will start on day -22, followed by infusion of donor NK (natural killer) cells on day-17, 6 doses of interleukin-2 (IL-2) to promote NK expansion (day -17 to day -7), 2 doses of ATG for additional immunosuppression to promote engraftment (day -5 to -4), and infusion of a TCR α/β-depleted same donor graft on day 0.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- Being tested
- Preparative Regimen, NK Cells, Interleukin-2, CD34 Graft/Anti-thymocyte globulin, Donor TCR α/β-depleted Graft/ATG
- Keywords
- non-myeloablative haploidentical transplant, hematopoietic cell transplant, natural killer cells, adoptive cellular therapy
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Preparative RegimenDrug
Also called Fludara, Cytoxan, radiation
Preparative Regimen:
- fludarabine 40 mg/m^2 x 4 doses on Days -22 through -19 pretransplant, 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pretransplant, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pretransplant,
NK CellsBiological
Also called Natural Killer cells
CD3^- CD19^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pretransplant.
Interleukin-2Drug
Also called IL-2
Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion
CD34 Graft/Anti-thymocyte globulinBiological
Also called ATG
Single donor filgrastim mobilized CD34+ selected peripheral blood stem cell graft (minimum cell dose of 5 x 10^6/kg) on day 0. Rabbit anti-thymocyte globulin (ATG) will be administered on day -1 (0.5 mg/kg) and day +1 and +2 (2.5 mg/kg) pretransplant per institutional guidelines. ATG dosing not identical for all patients.
Donor TCR α/β-depleted Graft/ATGBiological
Also called stem cell graft
Single donor TCR α/β-depleted filgrastim-mobilized peripheral blood stem cells (PBSC) graft (minimum cell dose of 5 x 10^6/kg) on day 0. ATG will be administered on days -6 and -5 (3mg/kg) for most patients.
| Study group | Role | What they receive |
|---|---|---|
| CD34 Schema - High-Risk Acute Myeloid Disease | Experimental | Patients with high risk acute myeloid disease treated with preparative regimen including Fludara, Cytoxan and total body irradiation followed by haploidentical donor NK cells, Interleukin-2, rabbit anti-thymocyte globulin, and filgrastim mobilized CD34+ selected peripheral blood stem cell graft from the same donor. Receives: Drug: Preparative Regimen; Biological: NK Cells; Drug: Interleukin-2; Biological: CD34 Graft/Anti-thymocyte globulin |
| TCRα/β Schema - High-Risk Acute Myeloid Disease | Experimental | Patients with high risk acute myeloid disease treated with preparative regimen including Fludara, Cytoxan and total body irradiation followed by haploidentical donor NK cells, Interleukin-2, rabbit anti-thymocyte globulin, and same donor TCR α/β-depleted cells infusion. Receives: Drug: Preparative Regimen; Biological: NK Cells; Drug: Interleukin-2; Biological: Donor TCR α/β-depleted Graft/ATG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Donor Neutrophil Engraftment
The rate of donor neutrophil engraftment in the absence of leukemia at day +28 will be determined. Successful neutrophil engraftment is defined as an absolute donor-derived neutrophil count of >500 cells/μl. Leukemia free is defined as <5% bone marrow blasts, absence of blasts with Auer rods; absence of extramedullary disease; but cytogenetic or molecular minimal residual disease is allowed.
Measured: Day 28
Secondary outcomes (4)
Number of Participants With Disease Free Survival
Measured: At 6 Months
Number of Participants With Treatment Related Mortality (TRM)
Cumulative incidence will be used to estimate TRM.
Measured: At 6 Months
Number of Participants Who Relapse
Cumulative incidence will be used to estimate relapse.
Measured: 2 Years
Number of Participants With Early In Vivo Expansion of Natural Killer (NK) Cells
Successful in vivo donor NK cell expansion will be defined by measuring an absolute circulating donor-derived NK cell count of >100 cells/μl in patient's peripheral blood 12 days after infusion.
Measured: Day 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2011 (estimated)
- Study startSep 2011
- Primary completionApr 2016
- Study completionApr 2017
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.
- Other trials for Acute Myeloid 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 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, M.D., Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01370213
- Sponsor's protocol ID
- 2011LS027
- Other IDs
- MT2011-05
- Status last verified
- Apr 2020
- First submitted
- 8 Jun 2011
- Last updated
- 13 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-Center Phase II Trial of NK Cell Based Non-Myeloablative Haploidentical Transplantation for Patients With High-Risk Acute Myeloid Diseases
- ClinicalTrials.gov ID
- NCT01370213
- Acronym / sponsor ID
- 2011LS027
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndrome
- Keywords
- non-myeloablative haploidentical transplant, hematopoietic cell transplant, natural killer cells, adoptive cellular therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Sep 2011
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 9 Jun 2011 (estimated)
- Results
- Posted 16 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II multi-institutional therapeutic study of NK-cell based nonmyeloablative haploidentical transplantation for the treatment of high-risk acute myeloid diseases. Enrollment will use a two-stage design. Stage 1 will enroll 15 patients unless an early stopping rule is met. If 9 or more of these first 15 patients achieve leukemia free neutrophil engraftment at day +28 accrual will move to stage 2. In stage 2, an additional 28 patients will be enrolled for a total of 43 patients. Patients will be followed for disease response for 2 years.
Detailed description
A reduced intensity conditioning using Fludara, Cytoxan, and irradiation will start on day -22, followed by infusion of donor NK (natural killer) cells on day-17, 6 doses of interleukin-2 (IL-2) to promote NK expansion (day -17 to day -7), 2 doses of ATG for additional immunosuppression to promote engraftment (day -5 to -4), and infusion of a TCR α/β-depleted same donor graft on day 0.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CD34 Schema - High-Risk Acute Myeloid Disease | Experimental | Drug: Preparative Regimen, Biological: NK Cells, Drug: Interleukin-2, Biological: CD34 Graft/Anti-thymocyte globulinPatients with high risk acute myeloid disease treated with preparative regimen including Fludara, Cytoxan and total body irradiation followed by haploidentical donor NK cells, Interleukin-2, rabbit anti-thymocyte globulin, and filgrastim mobilized CD34+ selected peripheral blood stem cell graft from the same donor. |
| TCRα/β Schema - High-Risk Acute Myeloid Disease | Experimental | Drug: Preparative Regimen, Biological: NK Cells, Drug: Interleukin-2, Biological: Donor TCR α/β-depleted Graft/ATGPatients with high risk acute myeloid disease treated with preparative regimen including Fludara, Cytoxan and total body irradiation followed by haploidentical donor NK cells, Interleukin-2, rabbit anti-thymocyte globulin, and same donor TCR α/β-depleted cells infusion. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)
- Primary induction failure (PIF): Patients who have not achieved a complete remission (CR) after two induction cycles of cytotoxic therapy (i.e. 7+ 3, MEC, FLAG, etc.) and having ≤ 10,000 absolute circulating blasts measured at least 21 days from prior therapy. Hydroxyurea may be used to control blasts count. Demethylating agents do not count as induction therapy; however early re-induction therapy based on residual disease on a day 14 BM will count as a 2nd cycle
- Relapsed Disease with low disease burden (AML or MDS with ≤ 10,000 absolute circulating blasts. No re-induction attempts are required, but a maximum of 2 reinduction attempts are allowed to be eligible.
- CR3 or greater: This will include CRp defined as CR without platelet recovery to 100,000/mcL.
- CR1 or CR2 with high risk features: Includes therapy induced, prior MDS or MPD, high risk cytogenetic or molecular phenotype with no available donor (sibling or unrelated adult)
Key exclusion criteria (15 listed)
- Biphenotypic leukemia
- Allogeneic transplant for AML within previous 6 months
- New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that has not been evaluated with bronchoscopy, if feasible. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
- Uncontrolled bacterial, fungal or viral infections including HIV - chronic asymptomatic viral hepatitis is allowed
- Known hypersensitivity to any of the study agents
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 |
|---|---|---|
| Preparative RegimenAlso: Fludara, Cytoxan, radiationPreparative Regimen: 1) fludarabine 40 mg/m^2 x 4 doses on Days -22 through -19 pretransplant, 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pretransplant, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pretransplant, | Drug | CD34 Schema - High-Risk Acute Myeloid Disease, TCRα/β Schema - High-Risk Acute Myeloid Disease |
| NK CellsAlso: Natural Killer cellsCD3^- CD19^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pretransplant. | Biological | CD34 Schema - High-Risk Acute Myeloid Disease, TCRα/β Schema - High-Risk Acute Myeloid Disease |
| Interleukin-2Also: IL-2Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion | Drug | CD34 Schema - High-Risk Acute Myeloid Disease, TCRα/β Schema - High-Risk Acute Myeloid Disease |
| CD34 Graft/Anti-thymocyte globulinAlso: ATGSingle donor filgrastim mobilized CD34+ selected peripheral blood stem cell graft (minimum cell dose of 5 x 10^6/kg) on day 0. Rabbit anti-thymocyte globulin (ATG) will be administered on day -1 (0.5 mg/kg) and day +1 and +2 (2.5 mg/kg) pretransplant per institutional guidelines. ATG dosing not identical for all patients. | Biological | CD34 Schema - High-Risk Acute Myeloid Disease |
| Donor TCR α/β-depleted Graft/ATGAlso: stem cell graftSingle donor TCR α/β-depleted filgrastim-mobilized peripheral blood stem cells (PBSC) graft (minimum cell dose of 5 x 10^6/kg) on day 0. ATG will be administered on days -6 and -5 (3mg/kg) for most patients. | Biological | TCRα/β Schema - High-Risk Acute Myeloid Disease |
Primary outcome
Number of Participants With Donor Neutrophil Engraftment
Time frame: Day 28
The rate of donor neutrophil engraftment in the absence of leukemia at day +28 will be determined. Successful neutrophil engraftment is defined as an absolute donor-derived neutrophil count of >500 cells/μl. Leukemia free is defined as <5% bone marrow blasts, absence of blasts with Auer rods; absence of extramedullary disease; but cytogenetic or molecular minimal residual disease is allowed.
4 secondary outcomes
Number of Participants With Disease Free Survival
Time frame: At 6 Months
Number of Participants With Treatment Related Mortality (TRM)
Time frame: At 6 Months
Number of Participants Who Relapse
Time frame: 2 Years
Number of Participants With Early In Vivo Expansion of Natural Killer (NK) Cells
Time frame: Day 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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, M.D. principal investigator
Masonic Cancer Center, University of Minnesota
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Preparative Regimen, NK Cells and Interleukin-2 in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by Masonic Cancer Center, University of Minnesota at 4 sites 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 17 inclusion and 15 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 13 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 16 Dec 2019). 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?
Number of Participants With Donor Neutrophil Engraftment (time frame: Day 28). 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 13 May 2020; AzTrials last refreshed its copy on 7 Nov 2026.