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
  Purpose

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 Intervention Phase
Leukemia
Biological: aldesleukin
Biological: therapeutic allogeneic lymphocytes
Drug: cyclophosphamide
Drug: fludarabine phosphate
Procedure: in vitro treated peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Natural Killer Cells in Patients With Relapsed Acute Myelogenous Leukemia

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Enrollment: 21
Study Start Date: March 2005
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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

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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00274846

Locations
United States, Minnesota
Masonic Cancer Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Study Chair: Jeffrey Miller, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided by Masonic Cancer Center, University of Minnesota

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00274846     History of Changes
Other Study ID Numbers: CDR0000450852, UMN-2004LS073, UMN-MT2004-25
Study First Received: January 10, 2006
Results First Received: July 24, 2009
Last Updated: November 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Aldesleukin
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on August 19, 2014