Haploidentical Natural Killer Cells to Treat Refractory or Relapsed Acute Myelogenous Leukemia (AML)
NCT ID: NCT01106950
Last Updated: 2017-12-28
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
15 participants
INTERVENTIONAL
2010-07-31
2012-12-31
Brief Summary
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Detailed Description
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All patients, including those who go on to transplant, will be followed to determine disease free survival, treatment related mortality, and time to relapse.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treated Patients
Patients are treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.
Natural Killer Cells
Given by infusion on Day 0. The product is T cell-depleted (CD3-) and B cell-depleted (CD19). Target dose for infusion is \< or = 8 x 10\^7 nucleated cells/kilogram.
Fludarabine
Administered as a 1 hour intravenous infusion once a day for 5 doses beginning on day -6.
Cyclophosphamide
Administered as a 2 hour intravenous infusion with high volume fluid flush and mesna per institutional guidelines on day -5 and -4 one hour after fludarabine infusion. (Day -4 administration may be omitted if patient has had a transplant in the previous 4 months.)
Denileukin diftitox
12 ug/kg/day will be administered on day -1 and day -2 intravenously.
Donor lymphapheresis
Day -1 before planned NK cell infusion, the donor will undergo lymphapheresis (Removal of lymphocytes from donated blood, with the remainder of the blood retransfused into the donor).
IL-2
Administered after NK cell infusion, 10 million units every other day for a total of 6 doses. (Patients weighing less than 45 kilograms will receive a dose of 5 million units/m\^2 every other day for 6 doses).
Interventions
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Natural Killer Cells
Given by infusion on Day 0. The product is T cell-depleted (CD3-) and B cell-depleted (CD19). Target dose for infusion is \< or = 8 x 10\^7 nucleated cells/kilogram.
Fludarabine
Administered as a 1 hour intravenous infusion once a day for 5 doses beginning on day -6.
Cyclophosphamide
Administered as a 2 hour intravenous infusion with high volume fluid flush and mesna per institutional guidelines on day -5 and -4 one hour after fludarabine infusion. (Day -4 administration may be omitted if patient has had a transplant in the previous 4 months.)
Denileukin diftitox
12 ug/kg/day will be administered on day -1 and day -2 intravenously.
Donor lymphapheresis
Day -1 before planned NK cell infusion, the donor will undergo lymphapheresis (Removal of lymphocytes from donated blood, with the remainder of the blood retransfused into the donor).
IL-2
Administered after NK cell infusion, 10 million units every other day for a total of 6 doses. (Patients weighing less than 45 kilograms will receive a dose of 5 million units/m\^2 every other day for 6 doses).
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Meets one of the following disease criteria:
* Primary acute myelogenous leukemia (AML) induction failure: no complete remission (CR) after 2 or more induction attempts
* Relapsed acute myelogenous leukemia (AML): not in CR after 1 or more cycles of standard re-induction therapy. 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
* blast count \< 30% within 10 days of starting protocol therapy
* Secondary AML from myelodysplastic syndrome (MDS)
* AML relapsed \> 2 months after transplant who do not have the option of donor lymphocyte infusions (e.g. recipients of autologous or umbilical cord blood \[UCB\] transplants) Patients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and CSF is clear for at least 2 weeks or magnetic resonance imaging (MRI) stable prior to enrollment. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment.
* Available related HLA-haploidentical donor (3-5 of 6 HLA-A, B and C)
* Karnofsky Performance Status \> 50% or Lansky Play score \> 50
* Adequate organ function defined as:
* Creatinine: ≤ 2.0 mg/dL (for pediatric patients - ClCr \> 50 ml/min or age adjusted Cr)
* Hepatic: Liver function tests (LFT's) \< 5 x upper limit of institutional normal (ULN)
* Pulmonary Function: oxygen saturation ≥ 90% on room air and pulmonary function \>50% corrected Diffusion lung capacity for carbon monoxide (DLCO) and Forced expiratory volume in one second (FEV1) Oxygen saturation \[\>92%\] can be used in child where pulmonary function tests (PFT's) cannot be obtained. (Testing required only if symptomatic or prior known impairment.)
* Cardiac Function: Ejection fraction (EF) ≥ 40%, no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
* Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to natural killer (NK) cell infusion (excluding denileukin diftitox pre-meds)
* Women of child bearing potential must have a negative pregnancy test within 14 days prior to study registration and agree to use adequate birth control during study treatment.
* Voluntary written consent
Exclusion Criteria
* Transplant \< 60 days prior to study enrollment
* New or progressive pulmonary infiltrates on screening chest x-ray or chest computated tomography (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). Surgical resection waives any waiting requirements.
* Uncontrolled bacterial or viral infections - chronic asymptomatic viral hepatitis is allowed
* Pleural effusion large enough to be detectable on chest x-ray
* Known hypersensitivity to any of the study agents used
* Received investigational drugs within the 14 days before enrollment
* Known active CNS involvement
2 Years
ALL
No
Sponsors
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Masonic Cancer Center, University of Minnesota
OTHER
Responsible Party
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Principal Investigators
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Jeffrey S. Miller, M.D.
Role: PRINCIPAL_INVESTIGATOR
Masonic Cancer Center, University of Minnesota
Locations
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Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Countries
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References
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Bachanova V, Cooley S, Defor TE, Verneris MR, Zhang B, McKenna DH, Curtsinger J, Panoskaltsis-Mortari A, Lewis D, Hippen K, McGlave P, Weisdorf DJ, Blazar BR, Miller JS. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood. 2014 Jun 19;123(25):3855-63. doi: 10.1182/blood-2013-10-532531. Epub 2014 Apr 9.
Other Identifiers
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MT2010-02
Identifier Type: OTHER
Identifier Source: secondary_id
1003M79954
Identifier Type: OTHER
Identifier Source: secondary_id
2010LS010
Identifier Type: -
Identifier Source: org_study_id