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Acute Myelogenous LeukemiaPhase 2NCT01639456

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

A Phase 2 study testing CD3-/CD19- natural killer cells, CD3-CD56+ natural killer cells and CliniMACS® CD3 and CD19 Reagent System in people with Acute Myelogenous Leukemia, run by Masonic Cancer Center, University of Minnesota at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Acute Myelogenous Leukemia
What is being tested?
CD3-/CD19- natural killer cells, CD3-CD56+ natural killer cells and CliniMACS® CD3 and CD19 Reagent System
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
Oct 2013to Jan 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • ≥ 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

Who cannot join

  • 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:
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

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)

Being tested
CD3-/CD19- natural killer cells, CD3-CD56+ natural killer cells, CliniMACS® CD3 and CD19 Reagent System, CliniMACS® CD56 Reagent System, Cyclophosphamide
Keywords
acute myelogenous leukemia
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CD3-/CD19- natural killer cellsBiological

    Infused on Day 0. The final CD3-/CD19- product must contain at least 20% NK cells based on previous studies using this cell product processing technique. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.

  • CD3-CD56+ natural killer cellsBiological

    Infused on Day 0. The final CD3-/CD56+ product must contain at least 70% NK cells based on a previous study using this cell product processing technique. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.

  • CliniMACS® CD3 and CD19 Reagent SystemDevice

    In combination used to simultaneously deplete CD3+ cells to remove T-lymphocytes and deplete CD19+ cells to remove B-lymphocytes (CD3-/CD19-). The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.

  • CliniMACS® CD56 Reagent SystemDevice

    CliniMACS® CD3 and CD19 Reagent System will be used in addition to CliniMACS® CD56 Reagent System to enrich CD56+ NK cells. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.

  • CyclophosphamideDrug

    Also called Cytoxin

    Infused intravenously 60 mg/kg x day -5

  • FludarabineDrug

    Also called Fludara

    Fludarabine 25 mg/m2 x days -6 through -2

  • AldesleukinDrug

    Also called IL-2

    IL-2 subcutaneously at 6 million units every other day for 6 doses - begin evening of the NK cell infusion.

Study groups in NCT01639456
Study groupRoleWhat they receive
Patients Using CD3-/CD19- NK cell productExperimentalPatients receive the apheresis product (collected day -1: enriched for NK cells using the CliniMACS® CD3 and CD19 Reagent System in combination with the large-scale tubing set (Miltenyi Biotec) to simultaneously deplete CD3+ cells to remove T-lymphocytes and deplete CD19+ cells to remove B-lymphocytes (CD3-/CD19- natural killer cells). Patients will also receive Cyclophosphamide, Fludarabine and Aldesleukin.
Receives: Biological: CD3-/CD19- natural killer cells; Device: CliniMACS® CD3 and CD19 Reagent System; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Aldesleukin
Patients Using CD3-/CD56+ purified NK cell productExperimentalPatients receive the apheresis product (collected day -1): purified for NK cells using the CliniMACS® CD3 Reagent System (Miltenyi Biotec) in combination with the large-scale tubing set to deplete CD3+ cells and then use the CliniMACS® CD56 Reagent System to enrich CD56+ NK cells (CD3-CD56+ natural killer cells). Patients will also receive Cyclophosphamide, Fludarabine and Aldesleukin.
Receives: Biological: CD3-CD56+ natural killer cells; Device: CliniMACS® CD3 and CD19 Reagent System; Device: CliniMACS® CD56 Reagent System; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Aldesleukin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease-Free Survival

    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.

    Measured: 1 Year

Secondary outcomes (6)

  1. Incidence of Infusional Toxicities

    Patients will be monitored for adverse effects of the NK cell infusion such as rash, acute allergic reaction, bronchospasm, respiratory distress, and acute vascular leak syndrome.

    Measured: Day 100

  2. Incidence of Chronic Graft-Versus-Host Disease (GVHD)

    Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.

    Measured: 1 Year

  3. Incidence of Acute Graft-Versus-Host Disease (GVHD)

    Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.

    Measured: Day 100

  4. Treatment-Related Mortality

    In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.

    Measured: Day 100, 1 Year and 2 Years

  5. Overall Survival

    The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate.

    Measured: 1 Year and 2 Years

  6. Disease-Free Survival

    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.

    Measured: 2 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2012 (estimated)
  2. Study startOct 2013
  3. Primary completionJan 2017 (estimated)
  4. Study completionJan 2017 (estimated)

Why it stopped: study was abandoned and a new study was written to replace this one

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01639456
Sponsor's protocol ID
2011LS151
Other IDs
MT2011-26
Status last verified
Nov 2017
First submitted
10 Jul 2012
Last updated
2 Dec 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CD3-/CD19- natural killer cells, CD3-CD56+ natural killer cells and CliniMACS® CD3 and CD19 Reagent System in people with Acute Myelogenous Leukemia, run by Masonic Cancer Center, University of Minnesota at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 2 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease-Free Survival (time frame: 1 Year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01639456.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2017.

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