search
Back to results

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

Primary Purpose

Acute Myelogenous Leukemia

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CD3-/CD19- natural killer cells
CD3-CD56+ natural killer cells
CliniMACS® CD3 and CD19 Reagent System
CliniMACS® CD56 Reagent System
Cyclophosphamide
Fludarabine
Aldesleukin
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring acute myelogenous leukemia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Masonic Cancer Center, University of Minnesota
  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Patients Using CD3-/CD19- NK cell product

Patients Using CD3-/CD56+ purified NK cell product

Arm Description

Patients 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.

Patients 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.

Full Information

First Posted
July 10, 2012
Last Updated
November 29, 2017
Sponsor
Masonic Cancer Center, University of Minnesota
Collaborators
Miltenyi Biomedicine GmbH
search

1. Study Identification

Unique Protocol Identification Number
NCT01639456
Brief Title
CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploid Donor Natural Killer Cell Treatment in Older AML in First Complete Remission
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Withdrawn
Why Stopped
study was abandoned and a new study was written to replace this one
Study Start Date
October 2013 (undefined)
Primary Completion Date
January 2017 (Anticipated)
Study Completion Date
January 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota
Collaborators
Miltenyi Biomedicine GmbH

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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: CD3-/CD19- NK cell product or 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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myelogenous Leukemia
Keywords
acute myelogenous leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Patients Using CD3-/CD19- NK cell product
Arm Type
Experimental
Arm Description
Patients 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.
Arm Title
Patients Using CD3-/CD56+ purified NK cell product
Arm Type
Experimental
Arm Description
Patients 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.
Intervention Type
Biological
Intervention Name(s)
CD3-/CD19- natural killer cells
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
CD3-CD56+ natural killer cells
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
CliniMACS® CD3 and CD19 Reagent System
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
CliniMACS® CD56 Reagent System
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxin
Intervention Description
Infused intravenously 60 mg/kg x day -5
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Fludarabine 25 mg/m2 x days -6 through -2
Intervention Type
Drug
Intervention Name(s)
Aldesleukin
Other Intervention Name(s)
IL-2
Intervention Description
IL-2 subcutaneously at 6 million units every other day for 6 doses - begin evening of the NK cell infusion.
Primary Outcome Measure Information:
Title
Disease-Free Survival
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.
Time Frame
1 Year
Secondary Outcome Measure Information:
Title
Incidence of Infusional Toxicities
Description
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.
Time Frame
Day 100
Title
Incidence of Chronic Graft-Versus-Host Disease (GVHD)
Description
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Time Frame
1 Year
Title
Incidence of Acute Graft-Versus-Host Disease (GVHD)
Description
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Time Frame
Day 100
Title
Treatment-Related Mortality
Description
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Time Frame
Day 100, 1 Year and 2 Years
Title
Overall Survival
Description
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.
Time Frame
1 Year and 2 Years
Title
Disease-Free Survival
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.
Time Frame
2 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey S. Miller, M.D.
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs