Haploidentical Natural Killer Cells to Treat Refractory or Relapsed Acute Myelogenous Leukemia (AML)

• Status: Terminated
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase II therapeutic study of related donor HLA-haploidentical NK-cell based therapy after a high dose of fludarabine/cyclophosphamide with denileukin diftitox preparative regimen for the treatment of poor prognosis acute myelogenous leukemia (AML).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Masonic Cancer Center, University of Minnesota
• Treatments: Cyclophosphamide; Denileukin diftitox; Fludarabine; Fludarabine phosphate; Interleukin-2

Criteria

Inclusion Criteria:

• ≥ 2 years of age

• 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:

• Bi-phenotypic acute leukemia

• 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