Haploidentical Donor Natural Killer Cell Infusion With IL-15 in Acute Myelogenous Leukemia (AML)

• Status: Completed
• Trial end date: 2015-03-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a single center, "modified standard design" dose escalation study designed to determine the maximum tolerated, minimum efficacious dose (MTD/MED) of IL-15 (Intravenous Recombinant Human IL-15) and incidence of donor natural killer (NK) cell expansion by day +14 when given after haploidentical donor NK cells in patients with relapse or refractory acute myelogenous leukemia (AML).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Masonic Cancer Center, University of Minnesota

Criteria

Inclusion Criteria:

• ≥ 18 years of age

• Meets one of the following disease criteria:

• Primary acute myelogenous leukemia (AML) induction failure: no complete response (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 induction therapy. For patients > 60 years of age the 1 cycle of standard chemotherapy is not required if either of the following is met:

• relapse within 6 months of last chemotherapy

• blast count <30% within 10 days of starting protocol

• 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 cerebrospinal fluid (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 donor (3-5 of 6 HLA-A, B and C)

• Karnofsky Performance Status > 50%

• Adequate organ function defined as:

• Creatinine: ≤ 2.0 mg/dL

• Hepatic: Liver function tests (LFT's) < 5 times upper limit of institutional normal (ULN)

• Pulmonary Function: oxygen saturation ≥ 90% on room air and pulmonary function >50% corrected DLCO and FEV1 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 preparative regimen pre-medications)

• Women of child bearing potential and men with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy.

• Voluntary written consent

Exclusion Criteria:

• Bi-phenotypic acute leukemia

• Transplant < 60 days prior to study enrollment

• Pregnant or breastfeeding - The agents used in this study include those that fall under Pregnancy Category D - have known teratogenic potential. Women of child bearing potential must have a negative pregnancy test within 14 days of study treatment start

• Active autoimmune disease

• History of severe asthma, presently on chronic medications (a history of mild asthma not requiring therapy is eligible)

• 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). 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

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 (low resolution)

• Not pregnant

• Agree to undergo donor viral screening panel

• Able and willing to undergo apheresis

• Voluntary written consent