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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00274846
First received: January 10, 2006
Last updated: November 6, 2012
Last verified: November 2012

January 10, 2006
November 6, 2012
March 2005
June 2008   (final data collection date for primary outcome measure)
Number of Patients With Natural Killer (NK) Cell Expansion [ Time Frame: Study Day 14 ] [ Designated as safety issue: No ]
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).
Not Provided
Complete list of historical versions of study NCT00274846 on ClinicalTrials.gov Archive Site
  • Number of Patients With Complete Remission [ Time Frame: Day 28-35 ] [ Designated as safety issue: No ]
    Clinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (< 1% blasts in bone marrow with neutrophil recovery).
  • Median Time to Disease Relapse (Months) [ Time Frame: From 1st Day of treatment until death or receipt of bone marrow transplant. ] [ Designated as safety issue: No ]
    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.
  • Overall Survival Time of Patients With Complete Remission [ Time Frame: From Day 1 of Treatment until death or patient received bone marrow transplant. ] [ Designated as safety issue: No ]
    Median number of months patients were alive after NK cell infusion.
  • Number of Patients With Complete Remission and Natural Killer Cell Expansion [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    Includes patients who had both a complete remission of disease and an expansion of natural killer cells.
Not Provided
Not Provided
Not Provided
 
Donor Peripheral Stem Cell Transplant in Treating Patients With Relapsed Acute Myeloid Leukemia
Allogeneic Natural Killer Cells in Patients With Relapsed Acute Myelogenous Leukemia

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • 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 Name: 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 Name: lymphocytes
  • Drug: cyclophosphamide
    Days -5 and -4: 60 mg/kg
    Other Name: Cytoxan
  • Drug: fludarabine phosphate
    Days -5 through -2: 25 mg/m^2
    Other Name: Fludara
  • Procedure: in vitro treated peripheral blood stem cell transplantation
    Day 0 infuse natural killer cells
    Other Name: Natural Killer Cells
Experimental: Intent-to-Treat
All patients treated with natural killer (NK) cells (at a dose of 1.5-8 x 10^7/kg.)
Interventions:
  • Biological: aldesleukin
  • Biological: therapeutic allogeneic lymphocytes
  • Drug: cyclophosphamide
  • Drug: fludarabine phosphate
  • Procedure: in vitro treated peripheral blood stem cell transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21
June 2008
June 2008   (final data collection date for primary outcome measure)

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
Both
2 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00274846
CDR0000450852, UMN-2004LS073, UMN-MT2004-25
Yes
Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
Not Provided
Study Chair: Jeffrey Miller, MD Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP