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Leukemia, Myelogenous, AcutePhase 2NCT01106950

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

A Phase 2 study testing Natural Killer Cells, Fludarabine and Cyclophosphamide in people with Leukemia, Myelogenous, Acute, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 2 years and older
Conditions the study is for
Leukemia, Myelogenous, Acute
What is being tested?
Natural Killer Cells, Fludarabine and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
Jul 2010to Dec 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 2 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • ≥ 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
Show all 18Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: Adoptive Transfer of Haploidentical Natural Killer Cells to Treat Refractory or Relapsed AML MT2010-02

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).

Read the detailed description

Patients achieving a complete remission and neutrophil recovery (ANC > 500) for at least 4 weeks will be considered for allogeneic transplant to prolong remission (independent of this study).

All patients, including those who go on to transplant, will be followed to determine disease free survival, treatment related mortality, and time to relapse.

Being tested
Natural Killer Cells, Fludarabine, Cyclophosphamide, Denileukin diftitox, Donor lymphapheresis
Keywords
acute myelogenous leukemia, primary acute myelogenous leukemia, secondary acute myelogenous leukemia, relapsed 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.

  • Natural Killer CellsBiological

    Given by infusion on Day 0. The product is T cell-depleted (CD3-) and B cell-depleted (CD19). Target dose for infusion is < or = 8 x 10^7 nucleated cells/kilogram.

  • FludarabineDrug

    Also called Fludara

    Administered as a 1 hour intravenous infusion once a day for 5 doses beginning on day -6.

  • CyclophosphamideDrug

    Also called Cytoxan

    Administered as a 2 hour intravenous infusion with high volume fluid flush and mesna per institutional guidelines on day -5 and -4 one hour after fludarabine infusion. (Day -4 administration may be omitted if patient has had a transplant in the previous 4 months.)

  • Denileukin diftitoxDrug

    Also called Ontak

    12 ug/kg/day will be administered on day -1 and day -2 intravenously.

  • Donor lymphapheresisProcedure or surgery

    Day -1 before planned NK cell infusion, the donor will undergo lymphapheresis (Removal of lymphocytes from donated blood, with the remainder of the blood retransfused into the donor).

  • IL-2Drug

    Also called Interleukin-2

    Administered after NK cell infusion, 10 million units every other day for a total of 6 doses. (Patients weighing less than 45 kilograms will receive a dose of 5 million units/m^2 every other day for 6 doses).

Study groups in NCT01106950
Study groupRoleWhat they receive
Treated PatientsExperimentalPatients are treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.
Receives: Biological: Natural Killer Cells; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Denileukin diftitox; Procedure: Donor lymphapheresis; Drug: IL-2

What is being measured

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

  1. Percent of Patients With Successful Expansion of Natural Killer Cells After Infusion

    The primary objective of this study was to estimate the incidence of in vivo expansion of natural killer (NK) cells 14 days after infusion of an allogeneic donor product enriched for NK progenitors. Successful in vivo donor NK cell expansion was defined by measuring an absolute circulating donor-derived NK cell count of >100 cells/ul in the patient's peripheral blood 14 days after infusion.

    Measured: Day 14

Secondary outcomes (5)

  1. Percent of Patients With Complete Remission of Disease

    Disease response was defined as complete remission (disease response) by morphologic criteria including <5% blasts in a moderately cellular or cellular marrow. Complete remission was also correlated with NK cell expansion in vivo, IL-15 levels and donor/recipient KIR B genotyping, and Treg depletion.

    Measured: At least 4 weeks after last dose (28 days)

  2. Percent of Patients With Disease Free Survival

    Number of patients alive and disease free at 6 months. 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: Month 6

  3. Percent of Patients With Incidence of Relapse

    Number of patients who have had a relapse(the return of disease after its apparent recovery/cessation) after obtaining a complete remission of their disease.

    Measured: Month 6

  4. Number of Patients With Treatment-Related Death

    Number of patients who died within the first 100 days of treatment due to toxicity.

    Measured: Day 100

  5. Percent of Patients With Natural Killer Cell Expansion Versus KIR Genotype Versus Treg Depletion

    Association between in vivo natural killer (NK) cell expansion and complete response without platelet recovery (CRp) with donor killer immunoglobulin-like (KIR) genotype and Treg depletion. In vivo donor NK cell expansion was correlated with regulatory T-cell (Treg) depletion as detected on flow cytometry.

    Measured: Day 14

Timeline

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

  1. First posted20 Apr 2010 (estimated)
  2. Study startJul 2010
  3. Primary completionOct 2011
  4. Study completionDec 2012

Why it stopped: study drug (Ontak) no longer available

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01106950
Sponsor's protocol ID
2010LS010
Other IDs
MT2010-02, 1003M79954
Status last verified
Dec 2017
First submitted
19 Apr 2010
Last updated
28 Dec 2017
Data monitoring committee
Yes

Publications

  • Bachanova V, Cooley S, Defor TE, Verneris MR, Zhang B, McKenna DH, Curtsinger J, Panoskaltsis-Mortari A, Lewis D, Hippen K, McGlave P, Weisdorf DJ, Blazar BR, Miller JS. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood. 2014 Jun 19;123(25):3855-63. doi: 10.1182/blood-2013-10-532531. Epub 2014 Apr 9.

    PubMed 24719405

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Natural Killer Cells, Fludarabine and Cyclophosphamide in people with Leukemia, Myelogenous, Acute, run by Masonic Cancer Center, University of Minnesota at 1 site 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 18 inclusion and 8 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: stopped early, as of the sponsor's last update on 28 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 1 site 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?

Yes. Results are posted in the registry (first posted 26 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percent of Patients With Successful Expansion of Natural Killer Cells After Infusion (time frame: Day 14). 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 NCT01106950, which also lists 1 linked publication.

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 28 Dec 2017.

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