CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploid Donor Natural Killer Cell Treatment in Older AML in First Complete Remission

• Status: Withdrawn
• Trial end date: 2017-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase II trial designed to test the safety and efficacy (disease free survival [DFS]) of related donor HLA-haploidentical NK-cell based therapy for the treatment of acute myelogenous leukemia (AML). The natural killer (NK) cell product will be given to patients 60 years and older who are in a first complete remission after 1 or 2 courses of standard AML induction. After a preparative regimen of cyclophosphamide and fludarabine, patients will receive a single infusion of either CD3-/CD19- NK cells or CD3-/CD56+ NK cells followed by a short course of Interleukin-2 (IL-2) to facilitate NK cell survival and expansion.

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

Details

• Lead Sponsor: Masonic Cancer Center, University of Minnesota
• Collaborators: Miltenyi Biomedicine GmbH; Miltenyi Biotec GmbH
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Vidarabine

Criteria

Inclusion Criteria:

• Diagnosis of acute myelogenous leukemia (except acute promyelocytic leukemia) in a first complete remission (CR1) and meet the following criteria:

• Meets the definition of complete remission by morphologic criteria including <5% blasts in a moderately cellular (> 20% cellularity) or cellular marrow.

• Complete remission (CR) was achieved after no more than 2 cycles of standard induction chemotherapy. Early re-induction therapy based on residual disease on a day 14 bone marrow (BM) will count as a 2nd cycle. Prior therapy with demethylating agents (i.e. azacitidine) is allowed, but patients must have attained CR after standard cytotoxic therapy (defined as absolute neutrophil count (ANC) > 1000 cells/μL, platelets > 100 x 10^9/L)

• No more than 3 months have lapsed from attainment of CR1

• No acute myelogenous leukemia (AML) consolidation therapy administered prior to enrollment

• Not a candidate for allogeneic stem cell transplantation

• ≥ 60 years of age

• Karnofsky performance status ≥ 70%

• Available related HLA haploidentical natural killer (NK) cell donor (sibling, offspring, or offspring of an HLA identical sibling) by at least Class I serologic typing at the A&B locus (donor age 18-75 years)

• At least 30 days since last dose of chemotherapy

• Adequate organ function within 14 days of enrollment defined as:

• Creatinine: ≤ 2.0 mg/dL

• Hepatic: aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) < 5 x upper limit of institutional normal (ULN)

• Pulmonary: oxygen saturation ≥ 90% on room air

• Cardiac: left ventricular ejection fraction (LVEF) by echocardiogram (ECHO or MUGA) ≥ 40%, no uncontrolled angina, uncontrolled atrial or ventricular arrhythmias, or evidence of acute ischemia or active conduction system abnormalities (rate controlled a-fib is not an exclusion)

• Ability to be off prednisone and other immunosuppressive drugs for at least 3 days prior to the NK cell infusion (excluding preparative regimen pre-meds)

• Voluntary written consent

Exclusion Criteria:

• Biphenotypic acute leukemia

• New progressive pulmonary infiltrates on screening chest x-ray or chest Computed Tomography scan that has not been evaluated with bronchoscopy (when 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 human immunodeficiency virus (HIV) - chronic asymptomatic viral hepatitis is allowed

• Pleural effusion large enough to be detectable on chest x-ray

• Known hypersensitivity to one or more of the study agents

Donor Selection:

• Related donor (sibling, offspring, or offspring of an HLA identical sibling) 18-75 years of age

• At least 40 kilograms

• In general good health as determined by the medical provider

• Negative for hepatitis and HIV on donor viral screen

• HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A&B locus

• Not pregnant

• Voluntary written consent