Acute Myeloid LeukemiaNCT00187096
Natural Killer (NK) Cell Transplantation for AML
A study testing Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2, Natural Killer Cell Infusion and CliniMACS System in people with Acute Myeloid Leukemia, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
The purpose of this study is to assess the safety and efficacy of infusing natural killer cells from a donor as treatment for patients with acute myeloid leukemia in remission or who have experienced relapse. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2, Natural Killer Cell Infusion and CliniMACS System
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Mar 2013
- Phase
- Interventional
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participants with AML that is in complete remission, is relapsed or refractory, or with increasing minimal residual disease.
- Participants in complete remission must have recovered from toxicity of previous therapy and have evidence of bone marrow recovery
- Participants who had prior stem cell transplant (SCT) must have no evidence of GVHD and 60 or more days have elapsed since the SCT.
Who cannot join
- Participants who are pregnant
- Participants with inadequate renal, liver, or pulmonary functions
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Official title: Pilot Study Of Haplo-Identical Natural Killer Cell Transplantation For Acute Myeloid Leukemia
The purpose of this study is to assess the safety and efficacy of infusing natural killer cells from a donor as treatment for patients with acute myeloid leukemia in remission or who have experienced relapse.
Read the detailed description
Natural killer (NK) cells extracted from a [parental] donor are infused intravenously. Most patients are given a multi-agent chemotherapeutic conditioning regimen prior to the infusion. The conditioning regimen may be omitted for patients who have previously received traditional stem cell transplant.
Details of Treatment Plan:
Stratum 1 (AML in complete remission)
Cyclophosphamide 60 mg/kg IV Day -7 Fludarabine 25 mg/m2/day IV Days -6 through -2 Donor pheresis Day -1 Start IL-2 on Day -1, then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0
Stratum 2 (AML that is refractory or relapsed or AML with increasing minimal residual disease)
Clofarabine 40 mg/m2 IV, days -6 through -2 Etoposide 100 mg/m2 IV, days -6 through -2 Cyclophosphamide 400 mg/m2 IV, days -6 through 02 Donor pheresis Day -1 Start IL-2 Day -1, and then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0.
For patients who have received prior SCT, the conditioning regimen may be omitted if the NK cells are obtained from the original SCT donor.
Cytokine regimen (stratum 1 and 2): 1 million units/m2 of IL-2 given subcutaneously three times per week for two weeks (6 doses) starting on the evening of day -1.
NK Cell Transplantation (stratum 1 and 2): NK cells from haplo-identical family donor will be infused on day 0.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2, Natural Killer Cell Infusion, CliniMACS System
- Keywords
- Leukemia, Myeloid, Acute
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2Drug
See Detailed Description section for additional details of treatment interventions.
Natural Killer Cell InfusionProcedure or surgery
See Detailed Description section for additional details of treatment interventions.
CliniMACS SystemDevice
See Detailed Description section for additional details of treatment interventions.
| Study group | Role | What they receive |
|---|---|---|
| Stratum 1 | Experimental | Stratum 1 (AML in complete remission)
Cyclophosphamide 60 mg/kg IV Day -7 Fludarabine 25 mg/m2/day IV Days -6 through -2 Donor pheresis Day -1 Start IL-2 on Day -1, then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0 Receives: Drug: Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2; Procedure: Natural Killer Cell Infusion; Device: CliniMACS System |
| Stratum 2 | Experimental | Stratum 2 (AML that is refractory or relapsed or AML with increasing minimal residual disease)
Clofarabine 40 mg/m2 IV, days -6 through -2 Etoposide 100 mg/m2 IV, days -6 through -2 Cyclophosphamide 400 mg/m2 IV, days -6 through 02 Donor pheresis Day -1 Start IL-2 Day -1, and then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0. Receives: Drug: Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2; Procedure: Natural Killer Cell Infusion; Device: CliniMACS System |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant
Document the number of patients experiencing grade 3 or 4 toxicities during conditioning and up to 100 days post-transplant. Toxicities were identified using Common Toxicity Criteria V 3.0 criteria.
Measured: Beginning at on therapy through 100 days post-transplant
Proportion of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant
Document the proportion of patients experiencing grade 3 or 4 toxicities during conditioning and up to 100 days post-transplant. Toxicities were identified using Common Toxicity Criteria V 3.0 criteria.
Measured: Beginning at on therapy through 100 days post-transplant
Secondary outcomes (8)
Duration of Engraftment of Natural Killer (NK) Cells
NK cell engraftment defined as NK cell chimerism in recipients.
Measured: Measured at days 2, 7, 14, 21 and 28 after NK cell transplantation, and up to 189 days post transplant as clinically indicated
Percent of Peak NK Cell Chimerism
The maximum percent of donor NK cell in recipients during a four-week period after NK cell infusion.
Measured: Days 2, 7, 14, 21 and 28 after NK cell transplantation
Percent of Detectable Donor NK Cells at Day 28
The percent of detectable donor NK cells in recipients at 28 days after NK cell infusion. Three of 10 participants had detectable donor cells at week 4. The results report the percent of detectable cells in the 3 participants.
Measured: At 28 days
Day That Maximum NK Cell Engraftment Was Reached
The time elapsed after transplantation in days until peak KIR-mismatched donor NK cell expansion was reached in recipients
Measured: Day 0 through Day 28 post NK cell transplantation
Number of KIR-mismatched NK Cells
Number of KIR-mismatched donor NK cells in recipients' blood at day 2 and day 14 post NK cell infusion.
Measured: Day 2 and day 14 post NK cell transplantation
Number of Participants With Evidence of NK Cells Lysing a Target Cell Line (K562)
NK cells in recipient achieving ability to lyse target cell line (K562) within normal range established by donor NK cells.
Measured: Days 2, 7, 14, 21, and 28 after NK cell transplantation
Relapse-free Survival
For Arm 1, the efficacy of NK cell transplantation will be reported as the proportion of participants who achieve complete or partial remission. Kaplan-Meier estimates of relapse-free survival and confidence interval was determined by binomial distribution because no events were observed. The binomial interval is based on the number of patients at risk.
Measured: Up to 2 years post NK cell transplantation
Overall Survival
Overall survival is defined as the time relapse from on study date to death with those alive at last follow up date censored. The Kaplan-Meier method was used to compute survival probability estimates and confidence interval was determined by binomial distribution (for no events or all events) or by log hazard method. The binomial interval is based on the number of patients at risk.
The confidence intervals for Arm 1 and Arm 2a were determined by binomial distribution.
The confidence interval for Arm 2b was determined by log hazard method.
Measured: Up to 2 years post NK cell transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startSep 2005
- Primary completionFeb 2012
- Study completionMar 2013
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 Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey E. Rubnitz, M.D., Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00187096
- Sponsor's protocol ID
- NKAML
- Status last verified
- Oct 2013
- First submitted
- 12 Sep 2005
- Last updated
- 19 Jun 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Rubnitz JE, Inaba H, Ribeiro RC, Pounds S, Rooney B, Bell T, Pui CH, Leung W. NKAML: a pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia. J Clin Oncol. 2010 Feb 20;28(6):955-9. doi: 10.1200/JCO.2009.24.4590. Epub 2010 Jan 19.
PubMed 20085940
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study Of Haplo-Identical Natural Killer Cell Transplantation For Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT00187096
- Acronym / sponsor ID
- NKAML
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Leukemia, Myeloid, Acute
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- Sep 2005
- Primary completion
- Feb 2012 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Posted 9 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety and efficacy of infusing natural killer cells from a donor as treatment for patients with acute myeloid leukemia in remission or who have experienced relapse.
Detailed description
Natural killer (NK) cells extracted from a [parental] donor are infused intravenously. Most patients are given a multi-agent chemotherapeutic conditioning regimen prior to the infusion. The conditioning regimen may be omitted for patients who have previously received traditional stem cell transplant.
Details of Treatment Plan:
Stratum 1 (AML in complete remission)
Cyclophosphamide 60 mg/kg IV Day -7 Fludarabine 25 mg/m2/day IV Days -6 through -2 Donor pheresis Day -1 Start IL-2 on Day -1, then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0
Stratum 2 (AML that is refractory or relapsed or AML with increasing minimal residual disease)
Clofarabine 40 mg/m2 IV, days -6 through -2 Etoposide 100 mg/m2 IV, days -6 through -2 Cyclophosphamide 400 mg/m2 IV, days -6 through 02 Donor pheresis Day -1 Start IL-2 Day -1, and then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0.
For patients who have received prior SCT, the conditioning regimen may be omitted if the NK cells are obtained from the original SCT donor.
Cytokine regimen (stratum 1 and 2): 1 million units/m2 of IL-2 given subcutaneously three times per week for two weeks (6 doses) starting on the evening of day -1.
NK Cell Transplantation (stratum 1 and 2): NK cells from haplo-identical family donor will be infused 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 |
|---|---|---|
| Stratum 1 | Experimental | Drug: Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2, Procedure: Natural Killer Cell Infusion, Device: CliniMACS SystemStratum 1 (AML in complete remission) Cyclophosphamide 60 mg/kg IV Day -7 Fludarabine 25 mg/m2/day IV Days -6 through -2 Donor pheresis Day -1 Start IL-2 on Day -1, then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0 |
| Stratum 2 | Experimental | Drug: Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2, Procedure: Natural Killer Cell Infusion, Device: CliniMACS SystemStratum 2 (AML that is refractory or relapsed or AML with increasing minimal residual disease) Clofarabine 40 mg/m2 IV, days -6 through -2 Etoposide 100 mg/m2 IV, days -6 through -2 Cyclophosphamide 400 mg/m2 IV, days -6 through 02 Donor pheresis Day -1 Start IL-2 Day -1, and then 3 times per week x 2 weeks NK Cell purification and infusion on Day 0. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Participants with AML that is in complete remission, is relapsed or refractory, or with increasing minimal residual disease.
- Participants in complete remission must have recovered from toxicity of previous therapy and have evidence of bone marrow recovery
- Participants who had prior stem cell transplant (SCT) must have no evidence of GVHD and 60 or more days have elapsed since the SCT.
Key exclusion criteria (2 listed)
- Participants who are pregnant
- Participants with inadequate renal, liver, or pulmonary functions
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 |
|---|---|---|
| Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2See Detailed Description section for additional details of treatment interventions. | Drug | Stratum 1, Stratum 2 |
| Natural Killer Cell InfusionSee Detailed Description section for additional details of treatment interventions. | Procedure or surgery | Stratum 1, Stratum 2 |
| CliniMACS SystemSee Detailed Description section for additional details of treatment interventions. | Device | Stratum 1, Stratum 2 |
Primary outcome
Number of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant
Time frame: Beginning at on therapy through 100 days post-transplant
Document the number of patients experiencing grade 3 or 4 toxicities during conditioning and up to 100 days post-transplant. Toxicities were identified using Common Toxicity Criteria V 3.0 criteria.
Proportion of Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant
Time frame: Beginning at on therapy through 100 days post-transplant
Document the proportion of patients experiencing grade 3 or 4 toxicities during conditioning and up to 100 days post-transplant. Toxicities were identified using Common Toxicity Criteria V 3.0 criteria.
8 secondary outcomes
Duration of Engraftment of Natural Killer (NK) Cells
Time frame: Measured at days 2, 7, 14, 21 and 28 after NK cell transplantation, and up to 189 days post transplant as clinically indicated
Percent of Peak NK Cell Chimerism
Time frame: Days 2, 7, 14, 21 and 28 after NK cell transplantation
Percent of Detectable Donor NK Cells at Day 28
Time frame: At 28 days
Day That Maximum NK Cell Engraftment Was Reached
Time frame: Day 0 through Day 28 post NK cell transplantation
Number of KIR-mismatched NK Cells
Time frame: Day 2 and day 14 post NK cell transplantation
Number of Participants With Evidence of NK Cells Lysing a Target Cell Line (K562)
Time frame: Days 2, 7, 14, 21, and 28 after NK cell transplantation
Relapse-free Survival
Time frame: Up to 2 years post NK cell transplantation
Overall Survival
Time frame: Up to 2 years post NK cell transplantation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20085940Rubnitz JE, Inaba H, Ribeiro RC, Pounds S, Rooney B, Bell T, Pui CH, Leung W. NKAML: a pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia. J Clin Oncol. 2010 Feb 20;28(6):955-9. doi: 10.1200/JCO.2009.24.4590. Epub 2010 Jan 19.
- St. Jude Children's Research HospitalLink provided by the sponsor.
Related trials for Acute Myeloid Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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 E. Rubnitz, M.D. principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cyclophosphamide, Fludarabine, Clofarabine, Etoposide, Interleukin-2, Natural Killer Cell Infusion and CliniMACS System in people with Acute Myeloid Leukemia, run by St. Jude Children's Research Hospital 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 3 inclusion and 2 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 19 Jun 2014. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Nov 2012). 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 Patients Experiencing Grade 3 or 4 Toxicities During Conditioning and up to 100 Days Post-transplant (time frame: Beginning at on therapy through 100 days post-transplant). The study lists 2 primary outcomes in all. 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 NCT00187096, 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 19 Jun 2014.