Donor Peripheral Stem Cell Transplant in Treating Patients With Relapsed Acute Myeloid Leukemia

Sponsor
Masonic Cancer Center, University of Minnesota (Other)
Overall Status
Completed
CT.gov ID
NCT00274846
Collaborator
(none)
21
Enrollment
1
Location
1
Arm
39
Duration (Months)
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells and natural killer (NK) cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This clinical trial is studying how well a peripheral stem cell transplant using NK cells from a donor works in treating patients with relapsed acute myeloid leukemia.

Condition or DiseaseIntervention/TreatmentPhase
  • Biological: aldesleukin
  • Biological: therapeutic allogeneic lymphocytes
  • Drug: cyclophosphamide
  • Drug: fludarabine phosphate
  • Procedure: in vitro treated peripheral blood stem cell transplantation
Phase 2

Detailed Description

OBJECTIVES:

Primary

  • Evaluate the in vivo expansion of natural killer (NK) cells 14 days after treatment with allogeneic NK cell-enriched peripheral blood stem cell transplantation in patients with relapsed acute myeloid leukemia.

Secondary

  • Determine the response rate, in terms of complete remission, in patients treated with this regimen.

  • Correlate complete remission rate with NK cell expansion, interleukin-15 levels, and donor/recipient killer immunoglobulin receptor (KIR) ligand matching status in patients treated with this regimen.

  • Determine the overall and progression-free survival of patients treated with this regimen.

  • Determine the toxicity of this regimen in these patients.

OUTLINE: This is an open-label study.

  • Induction therapy: Patients receive fludarabine IV on days -6 to -2 and cyclophosphamide IV on day -5 or on days -5 and -4.

  • Allogeneic natural killer (NK) cell-enriched peripheral blood stem cell transplantation: Patients receive allogeneic NK cell-enriched peripheral blood stem cells IV over 15-60 minutes on day 0. Patients also receive interleukin-2 subcutaneously beginning on day 0 and continuing 3 times a week for up to 2 weeks.

After completion of study treatment, patients are followed periodically for 3 months.

Study Design

Study Type:
Interventional
Actual Enrollment :
21 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Allogeneic Natural Killer Cells in Patients With Relapsed Acute Myelogenous Leukemia
Study Start Date :
Mar 1, 2005
Actual Primary Completion Date :
Jun 1, 2008
Actual Study Completion Date :
Jun 1, 2008

Arms and Interventions

ArmIntervention/Treatment
Experimental: Intent-to-Treat

All patients treated with natural killer (NK) cells (at a dose of 1.5-8 x 10^7/kg.)

Biological: aldesleukin
10 million units three times a week for a total of 6 doses. For any subject less than 45 kilograms the IL-2 will be given at 5 million units per meter squared three times weekly for a total of 6 doses
Other Names:
  • IL-2
  • Biological: therapeutic allogeneic lymphocytes
    Cells infused per kg. 1.5-8.0 x 10^7/kg Total cells infused(for 70 kg. adult) 1.05 - 5.6 x 10^9
    Other Names:
  • lymphocytes
  • Drug: cyclophosphamide
    Days -5 and -4: 60 mg/kg
    Other Names:
  • Cytoxan
  • Drug: fludarabine phosphate
    Days -5 through -2: 25 mg/m^2
    Other Names:
  • Fludara
  • Procedure: in vitro treated peripheral blood stem cell transplantation
    Day 0 infuse natural killer cells
    Other Names:
  • Natural Killer Cells
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Patients With Natural Killer (NK) Cell Expansion [Study Day 14]

      Evaluation of expansion of donor allogeneic natural killer (NK) cells at day 14 following infusion (>100 donor-derived NK cells per uL of patient blood detectable at day +14).

    Secondary Outcome Measures

    1. Number of Patients With Complete Remission [Day 28-35]

      Clinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (< 1% blasts in bone marrow with neutrophil recovery).

    2. Median Time to Disease Relapse (Months) [From 1st Day of treatment until death or receipt of bone marrow transplant.]

      Follow-up continued every 3 months after the allogeneic natural killer (NK) cell infusion, unless they were transplanted, relapsed or had progressive disease. Time in months to relapse of disease is calculcated from 1st day of treatment with NK cells. Relapse occurs when leukemia is detected in bone marrow or blood.

    3. Overall Survival Time of Patients With Complete Remission [From Day 1 of Treatment until death or patient received bone marrow transplant.]

      Median number of months patients were alive after NK cell infusion.

    4. Number of Patients With Complete Remission and Natural Killer Cell Expansion [Day 14]

      Includes patients who had both a complete remission of disease and an expansion of natural killer cells.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Diagnosis of acute myeloid leukemia (AML) meeting 1 of the following criteria:

    • Primary refractory disease (no complete response [CR] after ≥ 2 induction therapies)

    • Relapsed disease not in CR after ≥ 1 course of standard reinduction therapy

    • Secondary AML from myelodysplastic syndromes

    • Disease relapsed ≥ 2 months after transplant and no option of donor lymphocyte infusions (e.g., recipients of autologous or umbilical cord blood transplants)

    • Chronic myelogenous leukemia with myeloid blast crisis not in second chronic phase after at least one cycle of standard chemotherapy and imatinib

    • Over 60 years of age with relapse within 6 months after completion of last chemotherapy

    • Over 60 years of age with blast count < 30% within 10 days before study entry

    • Related HLA-haploidentical natural killer cell donor available

    • No severe organ damage (by clinical or laboratory assessment)

    • Performance status 50-100%

    • No evidence of active infection on chest X-ray

    • No active fungal infection

    Exclusion Criteria:
    • Active central nervous system (CNS) leukemia

    • Pleural effusions large enough to be detectable by chest x-ray

    • Pregnant or nursing (positive pregnancy test)

    • Fertile patients must use effective contraception

    • Less than 60 days since prior transplant

    • Less than 3 days since prior prednisone

    • Less than 3 days since other prior immunosuppressive medication

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Masonic Cancer CenterMinneapolisMinnesotaUnited States55455

    Sponsors and Collaborators

    • Masonic Cancer Center, University of Minnesota

    Investigators

    • Study Chair: Jeffrey Miller, MD, Masonic Cancer Center, University of Minnesota

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Masonic Cancer Center, University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT00274846
    Other Study ID Numbers:
    • CDR0000450852
    • UMN-2004LS073
    • UMN-MT2004-25
    First Posted:
    Jan 11, 2006
    Last Update Posted:
    Dec 28, 2017
    Last Verified:
    Dec 1, 2017

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitlePatients With Relapsed/Refractory Acute Myeloid Leukemia
    Arm/Group DescriptionPatients who met study criteria - relapsed or refractory acute myelogenous leukemia - and were enrolled.
    Period Title: Overall Study
    STARTED21
    COMPLETED20
    NOT COMPLETED1

    Baseline Characteristics

    Arm/Group TitlePatients With Relapsed/Refractory Acute Myeloid Leukemia
    Arm/Group DescriptionPatients who met study criteria - relapsed or refractory acute myelogenous leukemia - and were enrolled.
    Overall Participants21
    Age (Count of Participants)
    <=18 years
    3
    14.3%
    Between 18 and 65 years
    17
    81%
    >=65 years
    1
    4.8%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    40
    (18.8)
    Sex: Female, Male (Count of Participants)
    Female
    10
    47.6%
    Male
    11
    52.4%
    Region of Enrollment (participants) [Number]
    United States
    21
    100%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Patients With Natural Killer (NK) Cell Expansion
    DescriptionEvaluation of expansion of donor allogeneic natural killer (NK) cells at day 14 following infusion (>100 donor-derived NK cells per uL of patient blood detectable at day +14).
    Time FrameStudy Day 14

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePatients With Relapsed/Refractory AML - Evaluable Group
    Arm/Group DescriptionPatients who are evaluable; received adequate (dose of 1.5-8 x 10^7/kg natural killer (NK) cells 14 days after treatment with chemotherapy and allogeneic NK cell-enriched immune therapy.
    Measure Participants20
    Number [Participants]
    2
    9.5%
    2. Secondary Outcome
    TitleNumber of Patients With Complete Remission
    DescriptionClinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (< 1% blasts in bone marrow with neutrophil recovery).
    Time FrameDay 28-35

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePatients With Relapsed/Refractory AML - Evaluable Group
    Arm/Group DescriptionPatients who are evaluable; received adequate (dose of 1.5-8 x 10^7/kg natural killer (NK) cells 14 days after treatment with chemotherapy and allogeneic NK cell-enriched immune therapy.
    Measure Participants20
    Number [Participant]
    2
    3. Secondary Outcome
    TitleMedian Time to Disease Relapse (Months)
    DescriptionFollow-up continued every 3 months after the allogeneic natural killer (NK) cell infusion, unless they were transplanted, relapsed or had progressive disease. Time in months to relapse of disease is calculcated from 1st day of treatment with NK cells. Relapse occurs when leukemia is detected in bone marrow or blood.
    Time FrameFrom 1st Day of treatment until death or receipt of bone marrow transplant.

    Outcome Measure Data

    Analysis Population Description
    Only 2 of 20 patients that received adequate Natural Killer Cells achieved complete remission, and were therefore evaluable for the time to relapse endpoint.
    Arm/Group TitlePatients Achieving Complete Remission - Responders
    Arm/Group DescriptionPatients who achieved complete remission (CR) as judged by morphological criteria; only these patients can be judged for time to relapse.
    Measure Participants2
    Median (Full Range) [Months]
    7.3
    4. Secondary Outcome
    TitleOverall Survival Time of Patients With Complete Remission
    DescriptionMedian number of months patients were alive after NK cell infusion.
    Time FrameFrom Day 1 of Treatment until death or patient received bone marrow transplant.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitlePatients Achieving Complete Remission - Responders
    Arm/Group DescriptionPatients who achieved complete remission (CR) as judged by morphological criteria; only these patients can be judged for time to relapse.
    Measure Participants2
    Median (Full Range) [Months]
    13
    5. Secondary Outcome
    TitleNumber of Patients With Complete Remission and Natural Killer Cell Expansion
    DescriptionIncludes patients who had both a complete remission of disease and an expansion of natural killer cells.
    Time FrameDay 14

    Outcome Measure Data

    Analysis Population Description
    Unable to evaluate due to low complete remission rate.
    Arm/Group TitlePatients With Relapsed/Refractory AML - Evaluable Group
    Arm/Group DescriptionPatients who are evaluable; received adequate (dose of 1.5-8 x 10^7/kg natural killer (NK) cells 14 days after treatment with chemotherapy and allogeneic NK cell-enriched immune therapy.
    Measure Participants0

    Adverse Events

    Time FrameEvents were monitored from Day 1 of study through Day 60 post-natural killer cell infusion.
    Adverse Event Reporting Description All "other" adverse events that occurred were expected and not captured.
    Arm/Group TitlePatients With Relapsed/Refractory Acute Myeloid Leukemia
    Arm/Group DescriptionPatients who met study criteria - relapsed or refractory acute myelogenous leukemia - and were enrolled.
    All Cause Mortality
    Patients With Relapsed/Refractory Acute Myeloid Leukemia
    Affected / at Risk (%)# Events
    Total/ (NaN)
    Serious Adverse Events
    Patients With Relapsed/Refractory Acute Myeloid Leukemia
    Affected / at Risk (%)# Events
    Total19/21 (90.5%)
    Blood and lymphatic system disorders
    Hemorrhage, CNS1/21 (4.8%) 1
    Hemorrhage, lung1/21 (4.8%) 1
    General disorders
    Death due to progressive disease14/21 (66.7%) 14
    Infections and infestations
    Infection4/21 (19%) 4
    Nervous system disorders
    Leukoencephalopathy1/21 (4.8%) 1
    Other (Not Including Serious) Adverse Events
    Patients With Relapsed/Refractory Acute Myeloid Leukemia
    Affected / at Risk (%)# Events
    Total0/21 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleJeffrey Miller, M.D.
    OrganizationMasonic Cancer Center, University of Minnesota
    Phone612-625-7409
    Emailmille011@umn.edu
    Responsible Party:
    Masonic Cancer Center, University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT00274846
    Other Study ID Numbers:
    • CDR0000450852
    • UMN-2004LS073
    • UMN-MT2004-25
    First Posted:
    Jan 11, 2006
    Last Update Posted:
    Dec 28, 2017
    Last Verified:
    Dec 1, 2017