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A Randomized Trial Comparing CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy in Older Adults With Acute Myelogenous Leukemia in First Complete Remission


Phase 2
18 Years
75 Years
Not Enrolling
Both
Acute Myelogenous Leukemia

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Trial Information

A Randomized Trial Comparing CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy in Older Adults With Acute Myelogenous Leukemia in First Complete Remission


The trial will use a single-stage design and will take place in two parts. The first part
will support the selection of the better NK cell product as measured by in vivo NK cell
expansion. Successful in vivo NK cell expansion is defined as 40% donor DNA and 40% of
lymphocytes are NK cells at day 7 post infusion OR 20% donor DNA and 20% of lymphocytes are
NK cells at day 14 post infusion.

Part 1: 1:1 randomization with 10 patients per cohort to either:

1. CD3-/CD19- NK cell product or

2. CD3-/CD56+ purified NK cell product The product with better NK cell expansion will be
used for the rest of the trial. If the results and safety profile are equivalent, the
CD56+ selection approach will be used. If neither approach results in successful NK
cell expansion, the trial will be stopped and the platform redesigned.

Part 2: complete the trial by enrolling an additional 26 patients using the product deemed
successful during part 1 to estimate the primary endpoint (DFS at 12 months)


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Disease-Free Survival

Outcome Description:

the length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.

Outcome Time Frame:

1 Year

Safety Issue:

No

Principal Investigator

Jeffrey S. Miller, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota

Authority:

United States: Food and Drug Administration

Study ID:

2011LS151

NCT ID:

NCT01639456

Start Date:

June 2013

Completion Date:

January 2017

Related Keywords:

  • Acute Myelogenous Leukemia
  • acute myelogenous leukemia
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

Washington University School of MedicineSaint Louis, Missouri  63110
Masonic Cancer Center, University of MinnesotaMinneapolis, Minnesota  55455